Phytic acid (Inositol hexaphosphate) are phytichemicasl of the organic acid found abunadantly in nuts, sesame seeds, soybeans, wheat, pumpkin, beans, almonds, etc.
Health Benefits
1. Alzheimer's disease (AD)
In the evaluation of the protective and beneficial effects of phytic acid against amyloid-β (Aβ) pathology in MC65 cells and the Tg2576 mouse model, showed that there was a significant increase in brain levels of cytochrome oxidase and a decrease in lipid peroxidation with phytic acid administration. In a treatment paradigm, 12-month old Tg2576 and wild type mice were treated with 2% phytic acid or vehicle for 6 months. Brain levels of copper, iron, and zinc were unaffected. The effects of phytic acid were modest on the expression of AβPP trafficking-associated protein AP180, autophagy-associated proteins (beclin-1, LC3B), sirtuin 1, the ratio of phosphorylated AMP-activated protein kinase (PAMPK) to AMPK, soluble Aβ1-40, and insoluble Aβ1-42. These results suggest that phytic acid may provide a viable treatment option for AD, according to "Phytic acid as a potential treatment for alzheimer's pathology: evidence from animal and in vitro models" by Anekonda TS, Wadsworth TL, Sabin R, Frahler K, Harris C, Petriko B, Ralle M, Woltjer R, Quinn JF.(1)
2. Colorectal cancer
In the investigation of the effect of phytic acid (inositol hexaphosphate, IP6) as a potential adjuvant in treatment of colorectal carcinoma, found that all employed concentrations of IP6 or IP6/Ins decreased proliferation of the cell lines, with the maximum decrease being observed in HT-29 cells. Metabolic activity of treated cells differed in response to IP6 and IP6/Ins treatment; in HT-29 and SW-620 significant decrease was observed only at the highest concentration, whereas in SW-480 cells metabolic activity was lower at each concentration except 0.2 and 1 mM IP6 or IP6/Ins in 24-h incubation, according to "Effect of phytic acid and inositol on the proliferation and apoptosis of cells derived from colorectal carcinoma" by Schröterová L, Hasková P, Rudolf E, Cervinka M.(2)
3. Glucose Metabolism
In the evaluation of the effect of dietary feeding of rice bran and phytic acid on the glucose metabolism in high fat-fed C57BL/6N mice fed, the tested mice were given with either a high fat diet only (HF group) or a high fat diet supplemented with rice bran (HF-RB group) or phytic acid (HF-PA group) for 7 weeks, found that The control mice (NC group) received a normal diet. At the end of the experimental period, the HF group exhibited substantially higher blood glucose level than the NC group. However, the HF-RB and HF-PA groups showed a marked decrease in the blood glucose level relative to HF mice. Furthermore, significantly higher glucokinase (GK) activity and lower phosphoenolpyruvate carboxykinase (PEPCK) activity were observed in HF-RB and HF-PA mice compared with that of the NC and HF ones. It was also found that the glucose-6-phosphatase (G6pase) activity and hepatic glycogen concentration were considerably higher in HF-RB and HF-PA groups, respectively, than that of the HF mice, according to "Modulatory Effect of Rice Bran and Phytic Acid on Glucose Metabolism in High Fat-Fed C57BL/6N Mice" by Kim SM, Rico CW, Lee SC, Kang MY.(3)
4. Cholesterol-lowering effects
In the investigation of the effects of four types of antinutritional factor (phytic acid, stachyose, soy saponins and soy isoflavones) on lipoprotein levels in plasma of Japanese flounder Paralichthys olivaceus, found that addition of 0·2-0·8% phytic acid or 0·4-1·5% stachyose decreased plasma high-density lipoprotein cholesterol (HDL-C) levels, increased plasma low-density lipoprotein cholesterol (LDL-C) levels, thereby increasing the LDL-C:HDL-C ratio. By contrast, supplementation with 0·35-0·7% soy saponins generally depressed plasma TC levels and the LDL-C:HDL-C ratio. Supplementation with 0·35-0·7% soy isoflavones, however, increased plasma TC and TG levels. These results indicate that soy saponins may be partly responsible for the cholesterol-lowering effects of soybean meal, according to "Effects of antinutritional factors on plasma lipoprotein levels in Japanese flounder Paralichthys olivaceus" by Deng JM, Mai KS, Ai QH, Zhang WB, Wang XJ, Xu W, Liufu ZG, Cai YH, Chen W.(4)
5. Antiaging
In the evaluation of the anti aging effects of of the gel and cream containing niosomes entrapped with the rice bran bioactive compounds, including ferulic acid (F), γ-oryzanol (O), and phytic acid (P), found that the formulations containing niosomes entrapped with the rice bran bioactive compounds gave superior clinical anti-aging activity which can be applied as a novel skin product, according to "Anti-aging efficacy of topical formulations containing niosomes entrapped with rice bran bioactive compounds" by Manosroi A, Chutoprapat R, Abe M, Manosroi W, Manosroi J.(5)
6. Antioxidant activities and skin hydration effects
In the evaluation of antioxidant activities [by in vitro ORAC (oxygen radical absorbance capacity) and ex vivo lipid peroxidation inhibition assay] and in vivo human skin hydration effects of gel and cream containing the rice bran extracts entrapped in niosomes, found that Gel and cream containing the rice bran extracts entrapped in niosomes showed higher antioxidant activity (ORAC value) at 20-28 micromol of Trolox equivalents (TE) per gram of the sample than the placebo gel and cream which gave 16-18 micromolTE/g. Human sebum treated with these formulations showed more lipid peroxidation inhibition activity than with no treatment of about 1.5 times. The three different independent techniques including corneometer, vapometer and confocal Raman microspectroscopy (CRM) indicated the same trend in human skin hydration enhancement of the gel or cream formulations containing the rice bran extracts entrapped in niosomes of about 20, 3 and 30%, respectively, according to "Antioxidant activities and skin hydration effects of rice bran bioactive compounds entrapped in niosomes" by Manosroi A, Chutoprapat R, Sato Y, Miyamoto K, Hsueh K, Abe M, Manosroi W, Manosroi J.(6)
7. Antioxidant and antimicrobial properties
In the investigation of the nutritive and biological properties of the meal from Rapa Catozza Napoletana (RCN) (Brassica rapa L. var. rapa) cultivar seeds as a new and alternative source of proteins, found that RCN seed meal could be highly regarded as a component of human nutrition and animal feed for its good protein content, desirable amino acid profile and low antinutrient concentration. Results for the sample indicated appreciable antiradical activity and good properties for meal stability, according to "Chemical composition, antioxidant and antimicrobial properties of Rapa Catozza Napoletana (Brassica rapa L. var. rapa DC.) seed meal, a promising protein source of Campania region (southern Italy) horticultural germplasm" by Tenore GC, Troisi J, Di Fiore R, Basile A, Novellino E.(7)
8. Antioxidant and type 2 diabetes
In the evaluation of the antioxidant and type 2 diabetes related enzyme inhibition properties of phytic acid extract prepared from raw and traditionally processed local grains and vegetables collected from Kenya, showed that phytic acid extract from raw samples revealed 59%-89% of DPPH radical scavenging capacity, 27-3,526 mmol Fe(II)/g extract of reducing power, 20%-72% of α-amylase inhibition activity and 8%-91% of α-glucosidase inhibition activity. Cooking and roasting improved the antioxidant and health relevant functionality of phytic acid extracts obtained from Kenyan local vegetables and grains, respectively, according to "Antioxidant and type 2 diabetes related functional properties of phytic acid extract from Kenyan local food ingredients: effects of traditional processing methods' by Kunyanga CN, Imungi JK, Okoth MW, Biesalski HK, Vadivel V.(8)
9. Skin cancer
in the assessment of the protective effects of IP6 against UVB irradiationinduced injury and photocarcinogenesis by using HaCaT cells (human immortalized keratinocytes) and SKH1 hairless mice, found that treatment with IP6 also decreased UVB-induced apoptosis and caspase 3 activation. Topical application of IP6 followed by exposure to UVB irradiation in SKH1 hairless mice decreased tumor incidence and multiplicity as compared with control mice. Our results suggest that IP6 protects HaCaT cells from UVB-induced apoptosis and mice from UVB-induced tumors, according to "Protective effect of inositol hexaphosphate against UVB damage in HaCaT cells and skin carcinogenesis in SKH1 hairless mice" by Williams KA, Kolappaswamy K, Detolla LJ, Vucenik I.(9)
10. Cancer inhibition
A striking anticancer effect of IP6 was demonstrated in different experimental models, showed that IP6 holds great promise in our strategies for the prevention and treatment of cancer. IP6 plus inositol enhances the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves the quality of life, as shown in a pilot clinical trial. The data strongly argue for the use of IP6 plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans, according to "Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic' by Vucenik I, Shamsuddin AM.(10)
11. Bone mineral density
In the study of the influence of phytate consumption on bone mineral density, indicated that the results obtained seem to indicate that the adequate consumption of phytate may play an important role in the prevention of bone mineral density loss in postmenopausal women, according to "[The influence of consumption of phytate on the bone mass in posmenopausal women of Mallorca].[Article in Spanish]" by López-González AA, Grases F, Marí B, Vicente-Herrero MT, Costa-Bauzá A, Monroy N.(11)
12. Etc.
Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/20930278
(2) http://www.ncbi.nlm.nih.gov/pubmed/20127021
(3) http://www.ncbi.nlm.nih.gov/pubmed/20664725
(4) http://www.ncbi.nlm.nih.gov/pubmed/22268430
(5) http://www.ncbi.nlm.nih.gov/pubmed/22235888
(6) http://www.ncbi.nlm.nih.gov/pubmed/21449379
(7) http://www.ncbi.nlm.nih.gov/pubmed/22173690
(8) http://www.ncbi.nlm.nih.gov/pubmed/21895422
(9) http://www.ncbi.nlm.nih.gov/pubmed/21819680
(10) http://www.ncbi.nlm.nih.gov/pubmed/14608114
(11) http://www.ncbi.nlm.nih.gov/pubmed/21794821
Saturday, February 18, 2012
Phytochemicals in Foods - 11 Health Benefits of Piperine
Piperine is a phytochemical alkaloid in the class of organosulfur compound, found abundantly in white and black pepper, long pepper, etc.
Health Benefits
1. Anti bacterial activities
In the valuation of novel synthetic analogues of piperine as inhibitors of multidrug efflux pump NorA of Staphylococcus aureus, showed that a newly identified class of compounds derived from a natural amide, piperine, is more potent than the parent molecule in potentiating the activity of ciprofloxacin through the inhibition of the NorA efflux pump. These molecules may prove useful in augmenting the antibacterial activities of fluoroquinolones in a clinical setting, according to "Novel structural analogues of piperine as inhibitors of the NorA efflux pump of Staphylococcus aureus" by Ashwani Kumar, Inshad Ali Khan, Surrinder Koul, Jawahir Lal Koul, Subhash Chandra Taneja, Intzar Ali, Furqan Ali, Sandeep Sharma, Zahid Mehmood Mirza, Manoj Kumar, Pyare Lal Sangwan, Pankaj Gupta, Niranjan Thota and Ghulam Nabi Qazi(1)
2. Anti-inflammatory Effect
In the investigation of investigate the anti-inflammatory effect of piperine against adjuvant-induced arthritis in rats, an experimental model for rheumatoid arthritis and compared it with that of the non-steroidal anti-inflammatory drug indomethacin, found that Histopathological analysis of joints also revealed that synovial hyperplasia and mononuclear infiltration observed in arthritic rats were alleviated by piperine. Thus, the present study clearly indicated that piperine possesses promising anti-inflammatory effect against adjuvant-induced arthritis by suppressing inflammation and cartilage destruction, according to "Anti-inflammatory Effect of Piperine in Adjuvant-Induced Arthritic Rats-a Biochemical Approach" by Murunikkara V, Pragasam SJ, Kodandaraman G, Sabina EP, Rasool M.(2)
3. Murine breast cancer
In the investigation of the effects of piperine, a major pungent alkaloid present in Piper nigrum and Piper longum, on the tumor growth and metastasis of mouse 4T1 mammary carcinoma in vitro and in vivo, and elucidation of the underlying mechanisms, showed that Treatment of 4T1 cells with piperine (70-280 μmol/L) dose-dependently induced apoptosis of 4T1 cells, accompanying activation of caspase 3. The cells treated with piperine (140 and 280 μmol/L) significantly increased the percentage of cells in G(2)/M phase with a reduction in the expression of cyclin B1. Piperine (140 and 280 μmol/L) significantly decreased the expression of MMP-9 and MMP-13, and inhibited 4T1 cell migration in vitro. Injection of piperine (2.5 and 5 mg/kg) dose-dependently suppressed the primary 4T1 tumor growth and injection of piperine (5 mg/kg) significantly inhibited the lung metastasis, according to "Piperine suppresses tumor growth and metastasis in vitro and in vivo in a 4T1 murine breast cancer model" by Lai LH, Fu QH, Liu Y, Jiang K, Guo QM, Chen QY, Yan B, Wang QQ, Shen JG.(3)
4. Cytotoxicity
In the investigation of the protective effect of piperine treatment on corticosterone-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells, showed that piperine co-treatment revealed a differential effect on the cytotoxicity of corticosterone and had its maximum inhibitory effect at 1 μM. Piperine (1 μM) co-treatment also significantly decreased intracellular reactive oxygen species level, and enhanced superoxide dismutase activity and total glutathione level in corticosterone-treated PC12 cells. In addition, piperine (1 μM) co-treatment was found to reverse the decreased brain-derived neurotrophic factor (BDNF) mRNA level caused by corticosterone in PC12 cells, according to "Protective Effects of Piperine Against Corticosterone-Induced Neurotoxicity in PC12 Cells" by Mao QQ, Huang Z, Ip SP, Xian YF, Che CT.(4)
5. Human metabolic syndrome
In the examination of the dietary supplementation with piperine, the active principle of black pepper, to high carbohydrate, high fat (HCHF) diet-fed rats as a model of human metabolic syndrome. Rats were fed with either HCHF diet (carbohydrate, 52%; fat, 24%; 25% fructose in drinking water) or cornstarch (CS) diet for a total of 16 weeks. Diets of the treatment groups (CS + piperine and HCHF + piperine) were supplemented with piperine for the last 8 weeks of this protocol, found that After 16 weeks, rats fed with HCHF diet developed hypertension, elevated oxidative stress and inflammation-induced cardiac changes (infiltration of inflammatory cells in heart, increase in count and degranulation of mast cells in heart, cardiac fibrosis and increase in ventricular stiffness), reduced responsiveness of aortic rings, impaired glucose tolerance, abdominal obesity together with liver fibrosis, fat deposition and increased plasma liver enzymes. Supplementation with piperine (375 mg/kg food; approximately 30 mg/kg/day) in HCHF-fed rats normalized blood pressure, improved glucose tolerance and reactivity of aortic rings, reduced plasma parameters of oxidative stress and inflammation, attenuated cardiac and hepatic inflammatory cell infiltration and fibrosis and improved liver function, according to "Piperine Attenuates Cardiovascular, Liver and Metabolic Changes in High Carbohydrate, High Fat-Fed Rats" by Diwan V, Poudyal H, Brown L.(5)
6. Hypertension
In the study of the effects of curcuma and black pepper compounds on increased blood pressure and remodeling of aorta in the rat model of experimental NO-deficient hypertension, showed that administration of piperine or curcumin, less their combination, is able to partially prevent the increase of blood pressure caused by chronic L-NAME administration. The spices modify the remodeling of the wall of the aorta induced by hypertension. Our results show that independent administration of curcumin is more effective in preventing negative changes in blood vessel morphology accompanying hypertensive disease, according to"Spice up the hypertension diet - curcumin and piperine prevent remodeling of aorta in experimental L-NAME induced hypertension" by Hlavačková L, Janegová A, Uličná O, Janega P, Cerná A, Babál P.(6)
7. Synergistic effects
in the evaluation of the effects of curcumin alone and with adjuvant piperine against benzo(a)pyrene (BaP) induced oxidative stress in lungs of male Swiss albino mice, showed that BaP treatment alone did not alter significantly the GST activity. Pretreatment with curcumin increased the GST activity in BaP treated group, which was enhanced further upon synergistic treatment with piperine and curcumin. Therefore, combined administration of curcumin and piperine shall prove to be more effective in attenuating BaP induced toxicity, according to "Synergistic effects of piperine and curcumin in modulating benzo(a)pyrene induced redox imbalance in mice lungs" by Sehgal A, Kumar M, Jain M, Dhawan DK.(7)
8. Antimicrobial, antileishmanial and cytotoxic compounds
in the evaluation of the petroleum ether and chloroform extracts of the root of Piper chaba showed antimicrobial, antileishmanial and cytotoxic activities, led to the isolation of Bornyl piperate (1), piperlonguminine (2) and piperine (3), showed that the isolated compounds (1 and 2) showed potent antifungal activity when compared with standard drug Nystatin, and significant cytotoxic activity with the IC(50) values of 0.76 and 0.83 µg mL(-1), respectively. These compounds were also found to have weak antibacterial and antileishmanial activities. This is the first report about the antileishmanial activity of Piper isolates, according to "Antimicrobial, antileishmanial and cytotoxic compounds from Piper chaba" by
Sources
(1) http://jac.oxfordjournals.org/content/61/6/1270.full
(2) http://www.ncbi.nlm.nih.gov/pubmed/22389056
(3) http://www.ncbi.nlm.nih.gov/pubmed/22388073
(4) http://www.ncbi.nlm.nih.gov/pubmed/22205277
(5) http://www.ncbi.nlm.nih.gov/pubmed/22038304
(6) http://www.ncbi.nlm.nih.gov/pubmed/22005253
(7) http://www.ncbi.nlm.nih.gov/pubmed/21859361
(8) http://www.ncbi.nlm.nih.gov/pubmed/21834629
(9) http://www.ncbi.nlm.nih.gov/pubmed/21827816
(10) http://www.ncbi.nlm.nih.gov/pubmed/21802927
(11) http://www.ncbi.nlm.nih.gov/pubmed/21612376
Health Benefits
1. Anti bacterial activities
In the valuation of novel synthetic analogues of piperine as inhibitors of multidrug efflux pump NorA of Staphylococcus aureus, showed that a newly identified class of compounds derived from a natural amide, piperine, is more potent than the parent molecule in potentiating the activity of ciprofloxacin through the inhibition of the NorA efflux pump. These molecules may prove useful in augmenting the antibacterial activities of fluoroquinolones in a clinical setting, according to "Novel structural analogues of piperine as inhibitors of the NorA efflux pump of Staphylococcus aureus" by Ashwani Kumar, Inshad Ali Khan, Surrinder Koul, Jawahir Lal Koul, Subhash Chandra Taneja, Intzar Ali, Furqan Ali, Sandeep Sharma, Zahid Mehmood Mirza, Manoj Kumar, Pyare Lal Sangwan, Pankaj Gupta, Niranjan Thota and Ghulam Nabi Qazi(1)
2. Anti-inflammatory Effect
In the investigation of investigate the anti-inflammatory effect of piperine against adjuvant-induced arthritis in rats, an experimental model for rheumatoid arthritis and compared it with that of the non-steroidal anti-inflammatory drug indomethacin, found that Histopathological analysis of joints also revealed that synovial hyperplasia and mononuclear infiltration observed in arthritic rats were alleviated by piperine. Thus, the present study clearly indicated that piperine possesses promising anti-inflammatory effect against adjuvant-induced arthritis by suppressing inflammation and cartilage destruction, according to "Anti-inflammatory Effect of Piperine in Adjuvant-Induced Arthritic Rats-a Biochemical Approach" by Murunikkara V, Pragasam SJ, Kodandaraman G, Sabina EP, Rasool M.(2)
3. Murine breast cancer
In the investigation of the effects of piperine, a major pungent alkaloid present in Piper nigrum and Piper longum, on the tumor growth and metastasis of mouse 4T1 mammary carcinoma in vitro and in vivo, and elucidation of the underlying mechanisms, showed that Treatment of 4T1 cells with piperine (70-280 μmol/L) dose-dependently induced apoptosis of 4T1 cells, accompanying activation of caspase 3. The cells treated with piperine (140 and 280 μmol/L) significantly increased the percentage of cells in G(2)/M phase with a reduction in the expression of cyclin B1. Piperine (140 and 280 μmol/L) significantly decreased the expression of MMP-9 and MMP-13, and inhibited 4T1 cell migration in vitro. Injection of piperine (2.5 and 5 mg/kg) dose-dependently suppressed the primary 4T1 tumor growth and injection of piperine (5 mg/kg) significantly inhibited the lung metastasis, according to "Piperine suppresses tumor growth and metastasis in vitro and in vivo in a 4T1 murine breast cancer model" by Lai LH, Fu QH, Liu Y, Jiang K, Guo QM, Chen QY, Yan B, Wang QQ, Shen JG.(3)
4. Cytotoxicity
In the investigation of the protective effect of piperine treatment on corticosterone-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells, showed that piperine co-treatment revealed a differential effect on the cytotoxicity of corticosterone and had its maximum inhibitory effect at 1 μM. Piperine (1 μM) co-treatment also significantly decreased intracellular reactive oxygen species level, and enhanced superoxide dismutase activity and total glutathione level in corticosterone-treated PC12 cells. In addition, piperine (1 μM) co-treatment was found to reverse the decreased brain-derived neurotrophic factor (BDNF) mRNA level caused by corticosterone in PC12 cells, according to "Protective Effects of Piperine Against Corticosterone-Induced Neurotoxicity in PC12 Cells" by Mao QQ, Huang Z, Ip SP, Xian YF, Che CT.(4)
5. Human metabolic syndrome
In the examination of the dietary supplementation with piperine, the active principle of black pepper, to high carbohydrate, high fat (HCHF) diet-fed rats as a model of human metabolic syndrome. Rats were fed with either HCHF diet (carbohydrate, 52%; fat, 24%; 25% fructose in drinking water) or cornstarch (CS) diet for a total of 16 weeks. Diets of the treatment groups (CS + piperine and HCHF + piperine) were supplemented with piperine for the last 8 weeks of this protocol, found that After 16 weeks, rats fed with HCHF diet developed hypertension, elevated oxidative stress and inflammation-induced cardiac changes (infiltration of inflammatory cells in heart, increase in count and degranulation of mast cells in heart, cardiac fibrosis and increase in ventricular stiffness), reduced responsiveness of aortic rings, impaired glucose tolerance, abdominal obesity together with liver fibrosis, fat deposition and increased plasma liver enzymes. Supplementation with piperine (375 mg/kg food; approximately 30 mg/kg/day) in HCHF-fed rats normalized blood pressure, improved glucose tolerance and reactivity of aortic rings, reduced plasma parameters of oxidative stress and inflammation, attenuated cardiac and hepatic inflammatory cell infiltration and fibrosis and improved liver function, according to "Piperine Attenuates Cardiovascular, Liver and Metabolic Changes in High Carbohydrate, High Fat-Fed Rats" by Diwan V, Poudyal H, Brown L.(5)
6. Hypertension
In the study of the effects of curcuma and black pepper compounds on increased blood pressure and remodeling of aorta in the rat model of experimental NO-deficient hypertension, showed that administration of piperine or curcumin, less their combination, is able to partially prevent the increase of blood pressure caused by chronic L-NAME administration. The spices modify the remodeling of the wall of the aorta induced by hypertension. Our results show that independent administration of curcumin is more effective in preventing negative changes in blood vessel morphology accompanying hypertensive disease, according to"Spice up the hypertension diet - curcumin and piperine prevent remodeling of aorta in experimental L-NAME induced hypertension" by Hlavačková L, Janegová A, Uličná O, Janega P, Cerná A, Babál P.(6)
7. Synergistic effects
in the evaluation of the effects of curcumin alone and with adjuvant piperine against benzo(a)pyrene (BaP) induced oxidative stress in lungs of male Swiss albino mice, showed that BaP treatment alone did not alter significantly the GST activity. Pretreatment with curcumin increased the GST activity in BaP treated group, which was enhanced further upon synergistic treatment with piperine and curcumin. Therefore, combined administration of curcumin and piperine shall prove to be more effective in attenuating BaP induced toxicity, according to "Synergistic effects of piperine and curcumin in modulating benzo(a)pyrene induced redox imbalance in mice lungs" by Sehgal A, Kumar M, Jain M, Dhawan DK.(7)
8. Antimicrobial, antileishmanial and cytotoxic compounds
in the evaluation of the petroleum ether and chloroform extracts of the root of Piper chaba showed antimicrobial, antileishmanial and cytotoxic activities, led to the isolation of Bornyl piperate (1), piperlonguminine (2) and piperine (3), showed that the isolated compounds (1 and 2) showed potent antifungal activity when compared with standard drug Nystatin, and significant cytotoxic activity with the IC(50) values of 0.76 and 0.83 µg mL(-1), respectively. These compounds were also found to have weak antibacterial and antileishmanial activities. This is the first report about the antileishmanial activity of Piper isolates, according to "Antimicrobial, antileishmanial and cytotoxic compounds from Piper chaba" by
Naz T, Mosaddik A, Rahman MM, Muhammad I, Haque ME, Cho SK.(8)
9. Antigenotoxic effects
In the investigation of the antigenotoxic effects of curcumin and piperine separately and in combination against benzo(a)pyrene (BaP) induced DNA damage in lungs and livers of mice, found thatPretreatments of curcumin and curcumin plus piperine before administration of single dose of BaP significantly decreased the levels of 8-oxo-dG content and % DNA in the comet tail in both the tissues. Moreover, the genoprotective potential of curcumin plus piperine was significantly higher as compared to curcumin alone against BaP induced DNA damage, according to "Combined effects of curcumin and piperine in ameliorating benzo(a)pyrene induced DNA damage" by Sehgal A, Kumar M, Jain M, Dhawan DK.(9)
10. Multidrug resistant cancer cells
Over-expression of P-gp, MRP1 and BCRP in tumor cells is one of the important mechanisms leading to multidrug resistance (MDR), which impairs the efficacy of chemotherapy. P-gp, MRP1 and BCRP are ABC (ATP-Binding Cassette) transporters, piperine can potentiate the cytotoxicity of anti-cancer drugs in resistant sublines, such as MCF-7/DOX and A-549/DDP, which were derived from MCF-7 and A-549 cell lines. At a concentration of 50 μM piperine could reverse the resistance to doxorubicin 32.16 and 14.14 folds, respectively. It also re-sensitized cells to mitoxantrone 6.98 folds. In addition, long-term treatment of cells by piperine inhibits transcription of the corresponding ABC transporter genes, according to "Piperine, a piperidine alkaloid from Piper nigrum re-sensitizes P-gp, MRP1 and BCRP dependent multidrug resistant cancer cells" by Li S, Lei Y, Jia Y, Li N, Wink M, Ma Y.(10)
11. Cytosolic isoforms hCA I and II
In the examination of Caffeine and piperine extracted for inhibition of the human (h) cytosolic isoforms hCA I and II, indicated that The IC(50) values of caffeine against hCA I was of 55 mM, whereas that of piperine of 60 mM. The IC(50) values of caffeine and piperine against hCA II were of 2 mM. Although these are quite weak inhibitors they may constitute leads for developing tighter binding compounds, according to "Carbonic anhydrase I and II inhibition with natural products: caffeine and piperine" by Sethi KK, Sahoo SK, Pichikala JN, Suresh P.(11)
12. Etc.
9. Antigenotoxic effects
In the investigation of the antigenotoxic effects of curcumin and piperine separately and in combination against benzo(a)pyrene (BaP) induced DNA damage in lungs and livers of mice, found thatPretreatments of curcumin and curcumin plus piperine before administration of single dose of BaP significantly decreased the levels of 8-oxo-dG content and % DNA in the comet tail in both the tissues. Moreover, the genoprotective potential of curcumin plus piperine was significantly higher as compared to curcumin alone against BaP induced DNA damage, according to "Combined effects of curcumin and piperine in ameliorating benzo(a)pyrene induced DNA damage" by Sehgal A, Kumar M, Jain M, Dhawan DK.(9)
10. Multidrug resistant cancer cells
Over-expression of P-gp, MRP1 and BCRP in tumor cells is one of the important mechanisms leading to multidrug resistance (MDR), which impairs the efficacy of chemotherapy. P-gp, MRP1 and BCRP are ABC (ATP-Binding Cassette) transporters, piperine can potentiate the cytotoxicity of anti-cancer drugs in resistant sublines, such as MCF-7/DOX and A-549/DDP, which were derived from MCF-7 and A-549 cell lines. At a concentration of 50 μM piperine could reverse the resistance to doxorubicin 32.16 and 14.14 folds, respectively. It also re-sensitized cells to mitoxantrone 6.98 folds. In addition, long-term treatment of cells by piperine inhibits transcription of the corresponding ABC transporter genes, according to "Piperine, a piperidine alkaloid from Piper nigrum re-sensitizes P-gp, MRP1 and BCRP dependent multidrug resistant cancer cells" by Li S, Lei Y, Jia Y, Li N, Wink M, Ma Y.(10)
11. Cytosolic isoforms hCA I and II
In the examination of Caffeine and piperine extracted for inhibition of the human (h) cytosolic isoforms hCA I and II, indicated that The IC(50) values of caffeine against hCA I was of 55 mM, whereas that of piperine of 60 mM. The IC(50) values of caffeine and piperine against hCA II were of 2 mM. Although these are quite weak inhibitors they may constitute leads for developing tighter binding compounds, according to "Carbonic anhydrase I and II inhibition with natural products: caffeine and piperine" by Sethi KK, Sahoo SK, Pichikala JN, Suresh P.(11)
12. Etc.
Sources
(1) http://jac.oxfordjournals.org/content/61/6/1270.full
(2) http://www.ncbi.nlm.nih.gov/pubmed/22389056
(3) http://www.ncbi.nlm.nih.gov/pubmed/22388073
(4) http://www.ncbi.nlm.nih.gov/pubmed/22205277
(5) http://www.ncbi.nlm.nih.gov/pubmed/22038304
(6) http://www.ncbi.nlm.nih.gov/pubmed/22005253
(7) http://www.ncbi.nlm.nih.gov/pubmed/21859361
(8) http://www.ncbi.nlm.nih.gov/pubmed/21834629
(9) http://www.ncbi.nlm.nih.gov/pubmed/21827816
(10) http://www.ncbi.nlm.nih.gov/pubmed/21802927
(11) http://www.ncbi.nlm.nih.gov/pubmed/21612376
Phytochemicals in Foods - 11 Health Benefits of Allyl isothiocyanate
Allyl isothiocyanate is phytochemical containing sulfur in the class of organosulfur compound, found abundantly in horseradish, mustard, wasabi, etc.
Health Benefits
1. Brain Cancer
In the investigation of that AITC significantly decreased proliferation and viability of human brain malignant glioma GBM 8401 cells in a dose-dependent manner with IC50 9.25+/-0.69 microM for 24 h-treatment, showed that Pretreatment with specific inhibitors of caspase-3 (Z-DEVE-FMK) and -9 (Z-LEHD-FMK) significantly reduced caspase-3 and -9 activity in GBM 8401 cells. Western blot analysis and colorimetric assays also displayed that AITC caused a time-dependent increase in cytosolic cytochrome c, pro-caspase-9, Apaf-1, AIF, Endo G and the stimulated caspase-9 and -3 activity. Our results suggest that AITC is a potent anti-human brain malignant glioma drug and it shows a remarkable action on cell cycle arrest before commitment for apoptosis is reached, according to "Allyl isothiocyanate triggers G2/M phase arrest and apoptosis in human brain malignant glioma GBM 8401 cells through a mitochondria-dependent pathway' by Chen NG, Chen KT, Lu CC, Lan YH, Lai CH, Chung YT, Yang JS, Lin YC.(1)
2. Bladder cancer
Urinary concentrations of AITC equivalent are at least ten times higher than in the plasma, and tissue levels of AITC equivalent in the urinary bladder were 14-79 times higher than in other organs after oral AITC administration to rats. AITC may be most effective in the bladder as a cancer chemopreventive compound. AITC at high-dose levels also exhibit a low degree of cytotoxicity and genotoxicity in animal studies, but such adverse effects are unlikely in humans exposed to dietary levels of AITC. Overall, AITC exhibits many desirable attributes of a cancer chemopreventive agent, and further studies are warranted in order to elucidate its mechanism of action and to assess its protective activity in humans, according to "Allyl isothiocyanate as a cancer chemopreventive phytochemical" by Zhang Y.(2)
3. Antimicrobial effects
In the investigation of the antimicrobial effect of a chitosan coating+allyl isothiocyanate (AIT) and nisin against Salmonella on whole fresh cantaloupes, showed that The same coating treatment completely inactivated mold and yeast on cantaloupe at day 1 and no regrowth occurred even up to 14days of storage. Scanning electron microscopy revealed that cell membrane damage and leakage of intercellular components occurred as a result of the chitosan-AIT coating treatments. No visual changes in overall appearance and color of cantaloupe rind and flesh due to coating treatments were observed. These results indicate that the application of an antimicrobial coating may be an effective method for decontamination of cantaloupes, according to "Inactivation of Salmonella on whole cantaloupe by application of an antimicrobial coating containing chitosan and allyl isothiocyanate" by Chen W, Jin TZ, Gurtler JB, Geveke DJ, Fan X.(3)
4. Stress response
In the examination of the effects of AITC on heat shock protein (HSP) 70 expression in Caenorhabditis elegans and factors affecting the production of AITC from its precursor, sinigrin, a glucosinolate, in ground Brassica juncea cv. Vulcan seed as mustard has some potential as a biopesticide, found that AITC induced toxicity in C. elegans, as measured by HSP70 expression.• Conditions required for the conversion of sinigrin to AITC in ground B. juncea seed were determined.• The use of C. elegans as a bioassay to test AITC or mustard biopesticide efficacy is discussed, according to "Allyl isothiocyanate induced stress response in Caenorhabditis elegans" by Saini AK, Tyler RT, Shim YY, Reaney MJ.(4)
5. Anti cancers
In the review of whether AITC arrests human bladder cancer cells in mitosis and also induces apoptosis, suggested that AITC induced mitochondrion-mediated apoptosis, as shown by cytochrome c release from mitochondria to cytoplasm, activation of caspase-9 and caspase-3, and formation of TUNEL-positive cells. Inhibition of caspase-9 blocked AITC-induced apoptosis. Moreover, we found that apoptosis induction by AITC depended entirely on mitotic arrest and was mediated via Bcl-2 phosphorylation at Ser-70. Pre-arresting cells in G(1) phase by hydroxyurea abrogated both AITC-induced mitotic arrest and Bcl-2 phosphorylation. Overexpression of a Bcl-2 mutant prevented AITC from inducing apoptosis, according to "Allyl isothiocyanate arrests cancer cells in mitosis, and mitotic arrest in turn leads to apoptosis via Bcl-2 protein phosphorylation' by Geng F, Tang L, Li Y, Yang L, Choi KS, Kazim AL, Zhang Y.(5)
6. Anti-inflammatory effects
In the evaluation of the underlying mechanisms of the potential anti-inflammatory properties of allyl-isothiocyanate (AITC) were analysed in vitro and in vivo, showed that 1. AITC was slightly less potent than sulforaphane (used as a positive control) in down-regulating inflammation in LPS stimulated macrophages. A significant increase in nuclear Nrf2 and heme oxygenase 1 gene expression and only a moderate down-regulation of interleukin 1β and microRNA-155 levels due to AITC was found in mouse liver. Present data suggest that AITC exhibits potent anti-inflammatory activity in cultured macrophages in vitro but has only relatively little anti-inflammatory activity in mice in vivo, according to "Anti-inflammatory potential of allyl-isothiocyanate-role of Nrf2, NFκB and microRNA-155" by Wagner AE, Boesch-Saadatmandi C, Dose J, Schultheiss G, Rimbach G.(6)
7. Colorectal Cancer
In the study conducted by Department of Biology, Science Centre, The Chinese University of Hong Kong, AITC was shown to inhibit the proliferation of human metastatic colorectal adenocarcinoma SW620 cells in vitro by inducing cell cycle arrest at the G2/M phase, according to "Allyl isothiocyanate induces G2/M arrest in human colorectal adenocarcinoma SW620 cells through down-regulation of Cdc25B and Cdc25C" by Lau WS, Chen T, Wong YS.(7)
8. Prostate cancer
In the demonstartion of that allyl isothiocyanate (AITC), a constituent of cruciferous vegetables, significantly inhibits proliferation of cultured PC-3 (androgen-independent) and LNCaP (androgen-dependent) human prostate cancer cells in a dose-dependent manner with an IC(50) of approximately 15-17 micro M, found that A significant reduction in the expression of cyclin B1 protein (approximately 45%) was observed only in LNCaP cells. A 24 h exposure of PC-3 and LNCaP cells to an apoptosis-inducing concentration of AITC (20 micro M) resulted in a significant decrease (31-68%) in the levels of anti-apoptotic protein Bcl-2 in both cell lines, and approximately 58% reduction in Bcl-X(L) protein expression in LNCaP cells. In conclusion, it seems reasonable to hypothesize that AITC, and possibly other ITCs, may find use in the treatment of human prostate cancers, according to "Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits proliferation of human prostate cancer cells by causing G2/M arrest and inducing apoptosis" by Xiao D, Srivastava SK, Lew KL, Zeng Y, Hershberger P, Johnson CS, Trump DL, Singh SV.(8)
9. Health benefits
In the research of nutritional significance of parent glucosinolate sinigrin 50 μmol/kg b. w./day and its degradation product allyl isothiocyanate 25 μmol/kg b. w./day and 50 μmol/kg b. w./day for their influence on some parameters of carbohydrate and lipid metabolism in an animal rat model in vivo after their single (4 h) and 2 weeks oral administration, showed that the effect of SIN and AITC is multidirectional, indicating its impact on many organs like liver as well as pancreas, intestine in vivo action and rat adipocytes in vitro. Whilst consumption of cruciferous vegetables at levels currently considered "normal" seems to be beneficial to human health, this data suggest that any large increase in intake could conceivably lead to undesirable effect. This effect is potentiated with time of action of the examined compounds, whose influence is rather adverse for the majority of metabolic pathways, according to "Multidirectional time-dependent effect of sinigrin and allyl isothiocyanate on metabolic parameters in rats" by Okulicz M.(9)
10. White Blood Cells (WBCs)
In the investigation of the effects of AITC (dose=20 mg/kg body weight/day for 10 days, subcutaneous: s.c.) on the number of WBCs (total WBCs, lymphocytes, monocyte, neutrophil, basophil and eosinophil) and plasma corticosterone concentrations in adult male rats, showed that administration of AITC decreased significantly the number of total WBCs on days 1-4 post s.c. injection by 25-27%. AITC also decreased the number of lymphocytes on days 1-10 by 21-36% and monocyte on days 1-8 by 28-78%. However, administration of AITC increased the number of neutrophil on days 8-10 by 61-112%. AITC did not change the number of eosinophil and basophil. Plasma corticosterone concentrations during the experimental period were 4.7-8.4 times significantly higher in the AITC group than in the control group, indicating that AITC induced stress-responses, according to "Allyl isothiocyanate-induced changes in the distribution of white blood cells in rats" by Imaizumi K, Sato S, Sakakibara Y, Mori S, Ohkuma M, Kawashima Y, Ban T, Sasaki H, Tachiyashiki K.(10)
11. Liver cancer
In the investigation of the possible protective effect of allyl isothiocyanate (AITC) in nitrite- and nitrosamine-treated human hepatoma cells (HepG2) with the evaluation by cytotoxic effects and genotoxic effects determined by the single-cell gel electrophoresis (SCGE), showed that Allyl isothiocyanate treatment enhanced cell viability and reduced intracellular reactive oxygen species (ROS) production in both nitrite- and nitrosamine-treated cells significantly. In SCGE, when compared to untreated control cells, all of the treated groups caused increases in the tail intensity (%) such as nitrite at 17%, N-nitrosodimethylamine (NDMA) at 279%, N-nitrosodiethylamine (NDEA) at 324%, and N-nitrosomorpholine (NMOR) at 288%, according to "Effect of allyl isothiocyanate (AITC) in both nitrite- and nitrosamine-induced cell death, production of reactive oxygen species, and DNA damage by the single-cell gel electrophoresis (SCGE): does it have any protective effect on HepG2 cells?" by Erkekoğlu P, Baydar T.(11)
12. Etc.
Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/20596632
(2) http://www.ncbi.nlm.nih.gov/pubmed/19960458
(3) http://www.ncbi.nlm.nih.gov/pubmed/22361025
(4) http://www.ncbi.nlm.nih.gov/pubmed/22093285
(5) http://www.ncbi.nlm.nih.gov/pubmed/21778226
(6) http://www.ncbi.nlm.nih.gov/pubmed/21692985
(7) http://www.ncbi.nlm.nih.gov/pubmed/21472349
(8) http://www.ncbi.nlm.nih.gov/pubmed/12771033
(9) http://www.ncbi.nlm.nih.gov/pubmed/20809411
(10) http://www.ncbi.nlm.nih.gov/pubmed/20686346
(11) http://www.ncbi.nlm.nih.gov/pubmed/20448263
Health Benefits
1. Brain Cancer
In the investigation of that AITC significantly decreased proliferation and viability of human brain malignant glioma GBM 8401 cells in a dose-dependent manner with IC50 9.25+/-0.69 microM for 24 h-treatment, showed that Pretreatment with specific inhibitors of caspase-3 (Z-DEVE-FMK) and -9 (Z-LEHD-FMK) significantly reduced caspase-3 and -9 activity in GBM 8401 cells. Western blot analysis and colorimetric assays also displayed that AITC caused a time-dependent increase in cytosolic cytochrome c, pro-caspase-9, Apaf-1, AIF, Endo G and the stimulated caspase-9 and -3 activity. Our results suggest that AITC is a potent anti-human brain malignant glioma drug and it shows a remarkable action on cell cycle arrest before commitment for apoptosis is reached, according to "Allyl isothiocyanate triggers G2/M phase arrest and apoptosis in human brain malignant glioma GBM 8401 cells through a mitochondria-dependent pathway' by Chen NG, Chen KT, Lu CC, Lan YH, Lai CH, Chung YT, Yang JS, Lin YC.(1)
2. Bladder cancer
Urinary concentrations of AITC equivalent are at least ten times higher than in the plasma, and tissue levels of AITC equivalent in the urinary bladder were 14-79 times higher than in other organs after oral AITC administration to rats. AITC may be most effective in the bladder as a cancer chemopreventive compound. AITC at high-dose levels also exhibit a low degree of cytotoxicity and genotoxicity in animal studies, but such adverse effects are unlikely in humans exposed to dietary levels of AITC. Overall, AITC exhibits many desirable attributes of a cancer chemopreventive agent, and further studies are warranted in order to elucidate its mechanism of action and to assess its protective activity in humans, according to "Allyl isothiocyanate as a cancer chemopreventive phytochemical" by Zhang Y.(2)
3. Antimicrobial effects
In the investigation of the antimicrobial effect of a chitosan coating+allyl isothiocyanate (AIT) and nisin against Salmonella on whole fresh cantaloupes, showed that The same coating treatment completely inactivated mold and yeast on cantaloupe at day 1 and no regrowth occurred even up to 14days of storage. Scanning electron microscopy revealed that cell membrane damage and leakage of intercellular components occurred as a result of the chitosan-AIT coating treatments. No visual changes in overall appearance and color of cantaloupe rind and flesh due to coating treatments were observed. These results indicate that the application of an antimicrobial coating may be an effective method for decontamination of cantaloupes, according to "Inactivation of Salmonella on whole cantaloupe by application of an antimicrobial coating containing chitosan and allyl isothiocyanate" by Chen W, Jin TZ, Gurtler JB, Geveke DJ, Fan X.(3)
4. Stress response
In the examination of the effects of AITC on heat shock protein (HSP) 70 expression in Caenorhabditis elegans and factors affecting the production of AITC from its precursor, sinigrin, a glucosinolate, in ground Brassica juncea cv. Vulcan seed as mustard has some potential as a biopesticide, found that AITC induced toxicity in C. elegans, as measured by HSP70 expression.• Conditions required for the conversion of sinigrin to AITC in ground B. juncea seed were determined.• The use of C. elegans as a bioassay to test AITC or mustard biopesticide efficacy is discussed, according to "Allyl isothiocyanate induced stress response in Caenorhabditis elegans" by Saini AK, Tyler RT, Shim YY, Reaney MJ.(4)
5. Anti cancers
In the review of whether AITC arrests human bladder cancer cells in mitosis and also induces apoptosis, suggested that AITC induced mitochondrion-mediated apoptosis, as shown by cytochrome c release from mitochondria to cytoplasm, activation of caspase-9 and caspase-3, and formation of TUNEL-positive cells. Inhibition of caspase-9 blocked AITC-induced apoptosis. Moreover, we found that apoptosis induction by AITC depended entirely on mitotic arrest and was mediated via Bcl-2 phosphorylation at Ser-70. Pre-arresting cells in G(1) phase by hydroxyurea abrogated both AITC-induced mitotic arrest and Bcl-2 phosphorylation. Overexpression of a Bcl-2 mutant prevented AITC from inducing apoptosis, according to "Allyl isothiocyanate arrests cancer cells in mitosis, and mitotic arrest in turn leads to apoptosis via Bcl-2 protein phosphorylation' by Geng F, Tang L, Li Y, Yang L, Choi KS, Kazim AL, Zhang Y.(5)
6. Anti-inflammatory effects
In the evaluation of the underlying mechanisms of the potential anti-inflammatory properties of allyl-isothiocyanate (AITC) were analysed in vitro and in vivo, showed that 1. AITC was slightly less potent than sulforaphane (used as a positive control) in down-regulating inflammation in LPS stimulated macrophages. A significant increase in nuclear Nrf2 and heme oxygenase 1 gene expression and only a moderate down-regulation of interleukin 1β and microRNA-155 levels due to AITC was found in mouse liver. Present data suggest that AITC exhibits potent anti-inflammatory activity in cultured macrophages in vitro but has only relatively little anti-inflammatory activity in mice in vivo, according to "Anti-inflammatory potential of allyl-isothiocyanate-role of Nrf2, NFκB and microRNA-155" by Wagner AE, Boesch-Saadatmandi C, Dose J, Schultheiss G, Rimbach G.(6)
7. Colorectal Cancer
In the study conducted by Department of Biology, Science Centre, The Chinese University of Hong Kong, AITC was shown to inhibit the proliferation of human metastatic colorectal adenocarcinoma SW620 cells in vitro by inducing cell cycle arrest at the G2/M phase, according to "Allyl isothiocyanate induces G2/M arrest in human colorectal adenocarcinoma SW620 cells through down-regulation of Cdc25B and Cdc25C" by Lau WS, Chen T, Wong YS.(7)
8. Prostate cancer
In the demonstartion of that allyl isothiocyanate (AITC), a constituent of cruciferous vegetables, significantly inhibits proliferation of cultured PC-3 (androgen-independent) and LNCaP (androgen-dependent) human prostate cancer cells in a dose-dependent manner with an IC(50) of approximately 15-17 micro M, found that A significant reduction in the expression of cyclin B1 protein (approximately 45%) was observed only in LNCaP cells. A 24 h exposure of PC-3 and LNCaP cells to an apoptosis-inducing concentration of AITC (20 micro M) resulted in a significant decrease (31-68%) in the levels of anti-apoptotic protein Bcl-2 in both cell lines, and approximately 58% reduction in Bcl-X(L) protein expression in LNCaP cells. In conclusion, it seems reasonable to hypothesize that AITC, and possibly other ITCs, may find use in the treatment of human prostate cancers, according to "Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits proliferation of human prostate cancer cells by causing G2/M arrest and inducing apoptosis" by Xiao D, Srivastava SK, Lew KL, Zeng Y, Hershberger P, Johnson CS, Trump DL, Singh SV.(8)
9. Health benefits
In the research of nutritional significance of parent glucosinolate sinigrin 50 μmol/kg b. w./day and its degradation product allyl isothiocyanate 25 μmol/kg b. w./day and 50 μmol/kg b. w./day for their influence on some parameters of carbohydrate and lipid metabolism in an animal rat model in vivo after their single (4 h) and 2 weeks oral administration, showed that the effect of SIN and AITC is multidirectional, indicating its impact on many organs like liver as well as pancreas, intestine in vivo action and rat adipocytes in vitro. Whilst consumption of cruciferous vegetables at levels currently considered "normal" seems to be beneficial to human health, this data suggest that any large increase in intake could conceivably lead to undesirable effect. This effect is potentiated with time of action of the examined compounds, whose influence is rather adverse for the majority of metabolic pathways, according to "Multidirectional time-dependent effect of sinigrin and allyl isothiocyanate on metabolic parameters in rats" by Okulicz M.(9)
10. White Blood Cells (WBCs)
In the investigation of the effects of AITC (dose=20 mg/kg body weight/day for 10 days, subcutaneous: s.c.) on the number of WBCs (total WBCs, lymphocytes, monocyte, neutrophil, basophil and eosinophil) and plasma corticosterone concentrations in adult male rats, showed that administration of AITC decreased significantly the number of total WBCs on days 1-4 post s.c. injection by 25-27%. AITC also decreased the number of lymphocytes on days 1-10 by 21-36% and monocyte on days 1-8 by 28-78%. However, administration of AITC increased the number of neutrophil on days 8-10 by 61-112%. AITC did not change the number of eosinophil and basophil. Plasma corticosterone concentrations during the experimental period were 4.7-8.4 times significantly higher in the AITC group than in the control group, indicating that AITC induced stress-responses, according to "Allyl isothiocyanate-induced changes in the distribution of white blood cells in rats" by Imaizumi K, Sato S, Sakakibara Y, Mori S, Ohkuma M, Kawashima Y, Ban T, Sasaki H, Tachiyashiki K.(10)
11. Liver cancer
In the investigation of the possible protective effect of allyl isothiocyanate (AITC) in nitrite- and nitrosamine-treated human hepatoma cells (HepG2) with the evaluation by cytotoxic effects and genotoxic effects determined by the single-cell gel electrophoresis (SCGE), showed that Allyl isothiocyanate treatment enhanced cell viability and reduced intracellular reactive oxygen species (ROS) production in both nitrite- and nitrosamine-treated cells significantly. In SCGE, when compared to untreated control cells, all of the treated groups caused increases in the tail intensity (%) such as nitrite at 17%, N-nitrosodimethylamine (NDMA) at 279%, N-nitrosodiethylamine (NDEA) at 324%, and N-nitrosomorpholine (NMOR) at 288%, according to "Effect of allyl isothiocyanate (AITC) in both nitrite- and nitrosamine-induced cell death, production of reactive oxygen species, and DNA damage by the single-cell gel electrophoresis (SCGE): does it have any protective effect on HepG2 cells?" by Erkekoğlu P, Baydar T.(11)
12. Etc.
Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/20596632
(2) http://www.ncbi.nlm.nih.gov/pubmed/19960458
(3) http://www.ncbi.nlm.nih.gov/pubmed/22361025
(4) http://www.ncbi.nlm.nih.gov/pubmed/22093285
(5) http://www.ncbi.nlm.nih.gov/pubmed/21778226
(6) http://www.ncbi.nlm.nih.gov/pubmed/21692985
(7) http://www.ncbi.nlm.nih.gov/pubmed/21472349
(8) http://www.ncbi.nlm.nih.gov/pubmed/12771033
(9) http://www.ncbi.nlm.nih.gov/pubmed/20809411
(10) http://www.ncbi.nlm.nih.gov/pubmed/20686346
(11) http://www.ncbi.nlm.nih.gov/pubmed/20448263
Phytochemicals in Foods - 11 Health Benefits of Allicin
Allicin is phytochemical containing sulfur in the class of organosulfur compound, found abundantly in onion and garlic.
Health Benefits
1. Antibacterial activities
In the comparison of those of allicin and several clinically useful antibiotics using two representative bacteria commonly found in the human environment, Gram-positive S. aureus and Gram-negative Escherichia coli, indicated that The garlic extract had more potent anti-staphylococcal activity than an equal amount of allicin. In terms of antibiotic potency against Gram-positive and Gram-negative bacteria, authentic allicin had roughly 1-2% of the potency of streptomycin (vs. S. aureus), 8% of that of vancomycin (vs. S. aureus), and only 0.2% of that of colistin (vs. E. coli), according to "Antibacterial potential of garlic-derived allicin and its cancellation by sulfhydryl compounds" by Fujisawa H, Watanabe K, Suma K, Origuchi K, Matsufuji H, Seki T, Ariga T.(1)
2. Cognitive effects
In the assessment of the effects of allicin on endogenous antioxidant defenses in hippocampus of cognitively impaired aged mouse, showed that treatment of allicin significantly ameliorated ageing-induced cognitive dysfunction through enhancing of Nrf2 antioxidant signaling pathways. Therefore, allicin could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in aging and Alzheimer's disease, according to "Allicin ameliorates cognitive deficits ageing-induced learning and memory deficits through enhancing of Nrf2 antioxidant signaling pathways" by Li XH, Li CY, Lu JM, Tian RB, Wei J.(2)
3. Chronic Occupational Lead Poisoning
In the investigation of the therapeutic effects of garlic and comparison with d-penicillamine in patients with chronic lead poisoning, found that garlic seems safer clinically and as effective as d-penicillamine. Therefore, garlic can be recommended for the treatment of mild-to-moderate lead poisoning, according to "Comparison of Therapeutic Effects of Garlic and d-Penicillamine in Patients with Chronic Occupational Lead Poisoning, according to " Kianoush S, Balali-Mood M, Mousavi SR, Moradi V, Sadeghi M, Dadpour B, Rajabi O, Shakeri MT.(3)
4. Free radical scavenger capacity
In a theoretical study on the free radical scavenger capacity of α-mangostin in Mangosteen and its monoanion is analyzed using the density functional theory approximation, indicated that In thermodynamics and kinetics, α-mangostin and its deprotonated form are good free radical scavenger through the HAT mechanism, with the anionic (deprotonated) form being more reactive than the neutral one. Their capacity to scavenge OOH free radical is similar to that of carotenes, higher than that of allicin, much higher than that of melatonin and N-acetylcysteine amide, and about 15 times lower than that of 2-propenesulfenic acid, according to "Free radical scavenger properties of α-mangostin: thermodynamics and kinetics of HAT and RAF mechanisms" by Martínez A, Galano A, Vargas R.(4)
5. Antimicrobial activity
Alliums are inhibitory against all tested microorganisms such as bacteria, fungi, viruses, and parasites. Alliums inhibit multi-drug-resistant microorganisms and often work synergistically with common antimicrobials. Allium-derived antimicrobial compounds inhibit microorganisms by reacting with the sulfhydryl (SH) groups of cellular proteins, according to "Antimicrobial properties of allium species" by Kyung KH.(5)
6. Murine T-lymphocytes (EL-4)
In the investigation of the anti-proliferative and pro-apoptotic activities of allicin in murine T-lymphocytes (EL-4) and the mechanism of inducing apoptosis in vitro, found that allicin was effective in inhibiting the proliferation of EL-4 cells in vitro in a concentration-dependent manner. Further, allicin could induce the formation of apoptotic bodies, nuclear condensation, DNA spallation, and even activated the expression of caspase-3, -12 and cytochrome C (cyt C). Finally, allicin up-regulated the ratio of Bax/Bcl-2 and induced a mitochondrion membrane potential (MMP) decrease. Allicin induced apoptosis in EL-4 cells in a time- and concentration-dependent manner, in which the mitochondrial pathway might play a central role, according to "Allicin induces apoptosis in EL-4 cells in vitro by activation of expression of caspase-3 and -12 and up-regulation of the ratio of Bax/Bcl-2" by Wang Z, Liu Z, Cao Z, Li L.(6)
7. Anti tumor activities
The combination treatments using chemotherapeutic agents with distinct molecular mechanisms are considered more promising for higher efficacy; however, using multiple agents contributes to added toxicity, in-vitro and in-vivo studies in the last few decades, showed that some phytochemicals derived from 'natural products' such as fruits, vegetables and certain spices, referred to as chemopreventive agents, including capsaicin, trans-anethole, thymoquinone, diosgenin, allicin, can not only reduce the risk of acquiring specific cancer but also have been shown to suppress cancer cell proliferation, inhibit growth factor signaling pathways, induce apoptosis, inhibit nuclear factor-κB, AP-1, Akt, MAPK, Wnt, Notch, p53, AR, ER, and JAK-STAT, etc., activation pathways, inhibit angiogenesis, suppress the expression of antiapoptotic proteins, and inhibit cyclooxygenase-2, according to "Antitumor promoting potential of selected phytochemicals derived from spices: a review" by Rajput S, Mandal M.(7)
8. Antioxidants and anti cancers
In the evaluation of the potential anticancer effects of different type of processed garlic extracts on WEHI-164 tumor cells in inbred BALB/c mice and correlate the tumor growth rates with some garlic constituents, showed that three weeks following tumor inoculation, the mean tumor size in garlic extract-treated groups was reduced with significant reductions observed in the fresh and microwaved extract groups compared with the control group (P<.05). The antioxidant capacity and the amounts of allicin, flavonoids, and phenolic compounds in differentially processed garlic were evaluated and correlated with their anticancer activities, according to "Correlation between antioxidant activity of garlic extracts and WEHI-164 fibrosarcoma tumor growth in BALB/c mice" by Shirzad H, Taji F, Rafieian-Kopaei M.(8)
9. Dental caries and periodontitis
In the testing the antimicrobial activity of garlic allicin on oral pathogens associated with dental caries and periodontitis, found that the result support the traditional medicinal use of garlic and suggest the use of allicin for alleviating dental diseases, according to "Garlic allicin as a potential agent for controlling oral pathogens" by Bachrach G, Jamil A, Naor R, Tal G, Ludmer Z, Steinberg D.(9)
10. Prevention and treatment of the common cold
In the review the evidence supporting complementary and alternative medicine approaches to treatment and prevention of the common cold in adults, indicated that for prevention, vitamin C demonstrated benefit in a large meta-analysis, with possibly increased benefit in patients subjected to cold stress. There is inconsistent evidence for Asian ginseng (Panax ginseng) and North American ginseng (Panax quinquefolius). Allicin was highly effective in 1 small trial. For treatment, Echinacea purpurea is the most consistently useful variety; it was effective in 5 of 6 trials. Zinc lozenges were effective in 5 of 9 trials, likely owing to dose and formulation issues. Overall, the evidence suggests no benefit from probiotics for prevention or treatment of the common cold, according to "Complementary and alternative medicine for prevention and treatment of the common cold" by Nahas R, Balla A.(10)
11. Neuroprotective diseases
In the investigation of the neuroproyective effects of (1) flavonoid polyphenols like epigallocatechin 3-gallate (EGCG) from green tea and quercetin from apples; (2) non-flavonoid polyphenols such as curcumin from tumeric and resveratrol from grapes; (3) phenolic acids or phenolic diterpenes such as rosmarinic acid or carnosic acid, respectively, both from rosemary; and (4) organosulfur compounds including the isothiocyanate, L-sulforaphane, from broccoli and the thiosulfonate allicin, from garlic, indicated that alternative mechanisms of action have also been suggested for the neuroprotective effects of these compounds such as modulation of signal transduction cascades or effects on gene expression. Here, we review the literature pertaining to these various classes of nutraceutical antioxidants and discuss their potential therapeutic value in neurodegenerative diseases, according to "Nutraceutical antioxidants as novel neuroprotective agents" by Kelsey NA, Wilkins HM, Linseman DA.(11)
12. Etc.
Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/19734685
(2) http://www.ncbi.nlm.nih.gov/pubmed/22390900
(3) http://www.ncbi.nlm.nih.gov/pubmed/22151785
(4) http://www.ncbi.nlm.nih.gov/pubmed/21936544
(5) http://www.ncbi.nlm.nih.gov/pubmed/21903379
(6) http://www.ncbi.nlm.nih.gov/pubmed/21902562
(7) http://www.ncbi.nlm.nih.gov/pubmed/21876437
(8) http://www.ncbi.nlm.nih.gov/pubmed/21812650
(9) http://www.ncbi.nlm.nih.gov/pubmed/21548800
(10) http://www.ncbi.nlm.nih.gov/pubmed/21322286
(11) http://www.ncbi.nlm.nih.gov/pubmed/21060289
Health Benefits
1. Antibacterial activities
In the comparison of those of allicin and several clinically useful antibiotics using two representative bacteria commonly found in the human environment, Gram-positive S. aureus and Gram-negative Escherichia coli, indicated that The garlic extract had more potent anti-staphylococcal activity than an equal amount of allicin. In terms of antibiotic potency against Gram-positive and Gram-negative bacteria, authentic allicin had roughly 1-2% of the potency of streptomycin (vs. S. aureus), 8% of that of vancomycin (vs. S. aureus), and only 0.2% of that of colistin (vs. E. coli), according to "Antibacterial potential of garlic-derived allicin and its cancellation by sulfhydryl compounds" by Fujisawa H, Watanabe K, Suma K, Origuchi K, Matsufuji H, Seki T, Ariga T.(1)
2. Cognitive effects
In the assessment of the effects of allicin on endogenous antioxidant defenses in hippocampus of cognitively impaired aged mouse, showed that treatment of allicin significantly ameliorated ageing-induced cognitive dysfunction through enhancing of Nrf2 antioxidant signaling pathways. Therefore, allicin could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in aging and Alzheimer's disease, according to "Allicin ameliorates cognitive deficits ageing-induced learning and memory deficits through enhancing of Nrf2 antioxidant signaling pathways" by Li XH, Li CY, Lu JM, Tian RB, Wei J.(2)
3. Chronic Occupational Lead Poisoning
In the investigation of the therapeutic effects of garlic and comparison with d-penicillamine in patients with chronic lead poisoning, found that garlic seems safer clinically and as effective as d-penicillamine. Therefore, garlic can be recommended for the treatment of mild-to-moderate lead poisoning, according to "Comparison of Therapeutic Effects of Garlic and d-Penicillamine in Patients with Chronic Occupational Lead Poisoning, according to " Kianoush S, Balali-Mood M, Mousavi SR, Moradi V, Sadeghi M, Dadpour B, Rajabi O, Shakeri MT.(3)
4. Free radical scavenger capacity
In a theoretical study on the free radical scavenger capacity of α-mangostin in Mangosteen and its monoanion is analyzed using the density functional theory approximation, indicated that In thermodynamics and kinetics, α-mangostin and its deprotonated form are good free radical scavenger through the HAT mechanism, with the anionic (deprotonated) form being more reactive than the neutral one. Their capacity to scavenge OOH free radical is similar to that of carotenes, higher than that of allicin, much higher than that of melatonin and N-acetylcysteine amide, and about 15 times lower than that of 2-propenesulfenic acid, according to "Free radical scavenger properties of α-mangostin: thermodynamics and kinetics of HAT and RAF mechanisms" by Martínez A, Galano A, Vargas R.(4)
5. Antimicrobial activity
Alliums are inhibitory against all tested microorganisms such as bacteria, fungi, viruses, and parasites. Alliums inhibit multi-drug-resistant microorganisms and often work synergistically with common antimicrobials. Allium-derived antimicrobial compounds inhibit microorganisms by reacting with the sulfhydryl (SH) groups of cellular proteins, according to "Antimicrobial properties of allium species" by Kyung KH.(5)
6. Murine T-lymphocytes (EL-4)
In the investigation of the anti-proliferative and pro-apoptotic activities of allicin in murine T-lymphocytes (EL-4) and the mechanism of inducing apoptosis in vitro, found that allicin was effective in inhibiting the proliferation of EL-4 cells in vitro in a concentration-dependent manner. Further, allicin could induce the formation of apoptotic bodies, nuclear condensation, DNA spallation, and even activated the expression of caspase-3, -12 and cytochrome C (cyt C). Finally, allicin up-regulated the ratio of Bax/Bcl-2 and induced a mitochondrion membrane potential (MMP) decrease. Allicin induced apoptosis in EL-4 cells in a time- and concentration-dependent manner, in which the mitochondrial pathway might play a central role, according to "Allicin induces apoptosis in EL-4 cells in vitro by activation of expression of caspase-3 and -12 and up-regulation of the ratio of Bax/Bcl-2" by Wang Z, Liu Z, Cao Z, Li L.(6)
7. Anti tumor activities
The combination treatments using chemotherapeutic agents with distinct molecular mechanisms are considered more promising for higher efficacy; however, using multiple agents contributes to added toxicity, in-vitro and in-vivo studies in the last few decades, showed that some phytochemicals derived from 'natural products' such as fruits, vegetables and certain spices, referred to as chemopreventive agents, including capsaicin, trans-anethole, thymoquinone, diosgenin, allicin, can not only reduce the risk of acquiring specific cancer but also have been shown to suppress cancer cell proliferation, inhibit growth factor signaling pathways, induce apoptosis, inhibit nuclear factor-κB, AP-1, Akt, MAPK, Wnt, Notch, p53, AR, ER, and JAK-STAT, etc., activation pathways, inhibit angiogenesis, suppress the expression of antiapoptotic proteins, and inhibit cyclooxygenase-2, according to "Antitumor promoting potential of selected phytochemicals derived from spices: a review" by Rajput S, Mandal M.(7)
8. Antioxidants and anti cancers
In the evaluation of the potential anticancer effects of different type of processed garlic extracts on WEHI-164 tumor cells in inbred BALB/c mice and correlate the tumor growth rates with some garlic constituents, showed that three weeks following tumor inoculation, the mean tumor size in garlic extract-treated groups was reduced with significant reductions observed in the fresh and microwaved extract groups compared with the control group (P<.05). The antioxidant capacity and the amounts of allicin, flavonoids, and phenolic compounds in differentially processed garlic were evaluated and correlated with their anticancer activities, according to "Correlation between antioxidant activity of garlic extracts and WEHI-164 fibrosarcoma tumor growth in BALB/c mice" by Shirzad H, Taji F, Rafieian-Kopaei M.(8)
9. Dental caries and periodontitis
In the testing the antimicrobial activity of garlic allicin on oral pathogens associated with dental caries and periodontitis, found that the result support the traditional medicinal use of garlic and suggest the use of allicin for alleviating dental diseases, according to "Garlic allicin as a potential agent for controlling oral pathogens" by Bachrach G, Jamil A, Naor R, Tal G, Ludmer Z, Steinberg D.(9)
10. Prevention and treatment of the common cold
In the review the evidence supporting complementary and alternative medicine approaches to treatment and prevention of the common cold in adults, indicated that for prevention, vitamin C demonstrated benefit in a large meta-analysis, with possibly increased benefit in patients subjected to cold stress. There is inconsistent evidence for Asian ginseng (Panax ginseng) and North American ginseng (Panax quinquefolius). Allicin was highly effective in 1 small trial. For treatment, Echinacea purpurea is the most consistently useful variety; it was effective in 5 of 6 trials. Zinc lozenges were effective in 5 of 9 trials, likely owing to dose and formulation issues. Overall, the evidence suggests no benefit from probiotics for prevention or treatment of the common cold, according to "Complementary and alternative medicine for prevention and treatment of the common cold" by Nahas R, Balla A.(10)
11. Neuroprotective diseases
In the investigation of the neuroproyective effects of (1) flavonoid polyphenols like epigallocatechin 3-gallate (EGCG) from green tea and quercetin from apples; (2) non-flavonoid polyphenols such as curcumin from tumeric and resveratrol from grapes; (3) phenolic acids or phenolic diterpenes such as rosmarinic acid or carnosic acid, respectively, both from rosemary; and (4) organosulfur compounds including the isothiocyanate, L-sulforaphane, from broccoli and the thiosulfonate allicin, from garlic, indicated that alternative mechanisms of action have also been suggested for the neuroprotective effects of these compounds such as modulation of signal transduction cascades or effects on gene expression. Here, we review the literature pertaining to these various classes of nutraceutical antioxidants and discuss their potential therapeutic value in neurodegenerative diseases, according to "Nutraceutical antioxidants as novel neuroprotective agents" by Kelsey NA, Wilkins HM, Linseman DA.(11)
12. Etc.
Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/19734685
(2) http://www.ncbi.nlm.nih.gov/pubmed/22390900
(3) http://www.ncbi.nlm.nih.gov/pubmed/22151785
(4) http://www.ncbi.nlm.nih.gov/pubmed/21936544
(5) http://www.ncbi.nlm.nih.gov/pubmed/21903379
(6) http://www.ncbi.nlm.nih.gov/pubmed/21902562
(7) http://www.ncbi.nlm.nih.gov/pubmed/21876437
(8) http://www.ncbi.nlm.nih.gov/pubmed/21812650
(9) http://www.ncbi.nlm.nih.gov/pubmed/21548800
(10) http://www.ncbi.nlm.nih.gov/pubmed/21322286
(11) http://www.ncbi.nlm.nih.gov/pubmed/21060289
Phytochemicals in Foods - 10 Health Benefits of Alliin
Alliin (S-allyl-L-cysteine-S-oxide) is a phytochemical compound sulfoxide,. a derivative of the amino acid cysteine, belonging to the class of sulfur compounds, found abundantly in fresh garlic and onion.
Health Benefits
1. Antioxidant properties
In the investigation of the antioxidant properties of garlic compounds representing the four main chemical classes, alliin, allyl cysteine, allyl disulfide, and allicin, prepared by chemical synthesis or purification, showed that Alliin scavenged superoxide, while allyl cysteine and allyl disulfide did not react with superoxide. Allicin suppressed the formation of superoxide by the xanthine/xanthine oxidase system, probably via a thiol exchange mechanism. Alliin, allyl cysteine, and allyl disulfide all scavenged hydroxyl radicals; the rate constants calculated based on deoxyribose competitive assay were 1.4-1.7 x 10(10), 2.1-2.2 x 10(9), and 0.7-1.5 x 10(10) M (1) second(1), respectively, according to "The antioxidant properties of garlic compounds: allyl cysteine, alliin, allicin, and allyl disulfide" by Chung LY.(1)
2. Anti diabetes
In comparison of the production and therapeutic efficiency of alliin extracted from garlic leaves of plants grown under ex situ and in situ conditions, found that Alliin production noted ~50% enhancement in leaves from plants grown under in situ conditions. Serum glucose, triglycerides, total lipids, total cholesterol, low-density lipoprotein (LDL)-, and very low-density lipoprotein (VLDL)-cholesterol in diabetic rats treated with alliin produced from in situ grown plants noted significant reduction of ~54%, 15%, 14%, 20%, 24%, and 15%, while 35%, 14%, 10%, 12%, 17% and 11% reduction was noted in diabetic rats treated with alliin produced from ex situ grown plants in comparison with those administered with distilled water. High-density lipoprotein (HDL)-cholesterol did not show any significant change. Leaf extract of plants lowered serum enzyme levels (alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase) toward the norm better than glibenclamide, according to "Alliin obtained from leaf extract of garlic grown under in situ conditions possess higher therapeutic potency as analyzed in alloxan-induced diabetic rats" by Nasim SA, Dhir B, Kapoor R, Fatima S, Mahmooduzzafar, Mujib A.(2)
3. Antibacterial activity
In the investigation of an antimicrobial sulfur compound newly isolated from heated garlic extract, showed that the compound was CH₂=CH-CH₂-S-S-S-CH₂-CH(NH₂)COOH, 3-(allyltrisulfanyl)-2-aminopropanoic acid, a derivative of cysteine, presumably derived from alliin (S-allyl-L-cysteine sulfoxide). This novel compound has comparatively potent anti-yeast activity and rather weak antibacterial activity, similar to other antimicrobial compounds in garlic, according to "3-(allyltrisulfanyl)-2-aminopropanoic acid, a novel nonvolatile water-soluble antimicrobial sulfur compound in heated garlic" by Kang SS, Lim DR, Kyung KH.(3)
4. Ovarian cancer
In the investigation of a chemical conjugate between daidzein and the garlic enzyme alliinase and its effect on human ovarian cancer cells, suggest that the targeted alliinase conjugates in the presence of alliin, generated therapeutically effective levels of allicin which were capable of suppressing tumor progression of intraperitoneal ovarian cancer in an animal model, according to "Conjugates of daidzein-alliinase as a targeted pro-drug enzyme system against ovarian carcinoma" by Appel E, Rabinkov A, Neeman M, Kohen F, Mirelman D.(4)
5. Mitochondrial dysfunction
In the evaluation of the preventive role of S-allyl cysteine sulphoxide (SACS) in isoproterenol (ISO)-induced cardiotoxicity in male Wistar rats, showed that oral administration of SACS for a period of 35 days to the normal control rats did not show any significant effect. Histopathological studies of the myocardial tissue showed a protective role of SACS in the myocardial-infarcted rats. The effect at a dose of SACS 80 mg/kg was more effective than the dose 40 mg/kg. The results of the study conclude that SACS protect the mitochondria of the ISO-induced myocardial-infarcted rats, according to 'Preventive effect of S-allyl cysteine sulphoxide (Alliin) on mitochondrial dysfunction in normal and isoproterenol induced cardiotoxicity in male Wistar rats: a histopathological study" by Sangeetha T, Darlin Quine S.(5)
6. Anti-fungal efficacy
In the evaluation of the in vitro anti-fungal efficacy of the active principle of garlic, pure allicin and polybutylcyanoacrylate (PBCA) nanoparticles (NPs) loaded with allicin.
found that that pure allicin has stronger in vitro anti-fungal efficacy to six tested fungi than alliinase and alliin. Moreover, it has improved significantly after pure allicin being wrapped into PBCA NP, which may be due to the NP's good prolonged release effect and nano-scale dimensions, according to "Anti-fungal efficacy of polybutylcyanoacrylate nanoparticles of allicin and comparison with pure allicin" by Luo DQ, Guo JH, Wang FJ, Jin ZX, Cheng XL, Zhu JC, Peng CQ, Zhang C.(6)
7. Antithrombotic and anticancer effects
In the review of modern scientific research has revealed that the wide variety of dietary and medicinal functions of garlic can be attributed to the sulfur compounds present in or generated from garlic, indicated that although garlic produces more than 20 kinds of sulfide compounds from a few sulfur-containing amino acids, their functions are different from one another; e.g., allicin, methyl allyl trisulfide, and diallyl trisulfide have antibacterial, antithrombotic, and anticancer activities, respectively, according to "Antithrombotic and anticancer effects of garlic-derived sulfur compounds: a review" by Ariga T, Seki T. (7)
8. Anti-angiogenesis
In the demonstartion of dose-dependent of Alliin, a compound derived from garlic, in inhibition of fibroblast growth factor-2 (FGF2)-induced human endothelial cell (EC) tube formation and angiogenesis in the chick chorioallantoic membrane (CAM) model, showed that these data indicated a synergistic effect of antioxidants on the anti-angiogenesis and anticancer efficacy of alliin. These data also suggest the implication of cellular NO and p53 as mediators of anti-angiogenesis and anticancer effects of alliin, according to "Anti-angiogenesis efficacy of the garlic ingredient alliin and antioxidants: role of nitric oxide and p53" by Mousa AS, Mousa SA.(8)
9. Serum lipids, blood pressure and arterial stiffness
in the testing the effect of dried garlic (Allium sativum) powder on blood lipids, blood pressure and arterial stiffness in a 12-week randomised, double-blind, placebo-controlled trial. Seventy-five healthy, normo-lipidaemic volunteers (men and women aged 40-60 years) were assigned to dried garlic powder tablets (10.8 mg alliin (3-(2-propenylsulfinyl)-L-alanine)/d, corresponding to about three garlic cloves) or placebo, showed that garlic powder was associated with a near-significant decrease (12 %) in triacylglycerol concentration (P=0.07). In conclusion, garlic powder tablets have no clinically relevant lipid-lowering and blood pressure-lowering effects in middle-aged, normo-lipidaemic individuals. The putative anti-atherosclerotic effect of garlic may be linked to risk markers other than blood lipids, according to "Effect of garlic (Allium sativum) powder tablets on serum lipids, blood pressure and arterial stiffness in normo-lipidaemic volunteers: a randomised, double-blind, placebo-controlled trial" by Turner B, Mølgaard C, Marckmann P.(9)
10. Hepatoprotective effect
In the study of the interaction of the non-protein amino acid alliin with the enzyme alliinase (alliin lyase, EC 4.4.1.4). D-Galactosamine highly sensitizes the host response of the experimental animal to endotoxin (lipopolysaccharide) and causes fulminant hepatitis within 8h after administration, indicated that In D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced hepatitis rats, a significant increase of lipid peroxidation and decreased liver antioxidant enzyme levels are observed. Pretreatment with allicin, the active component of freshly crushed garlic cloves, prevented these alterations, according to "Hepatoprotective effect of allicin on tissue defense system in galactosamine/endotoxin challenged rats" by Vimal V, Devaki T.(10)
11. Etc.
Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/16822206
(2) http://www.ncbi.nlm.nih.gov/pubmed/21391887
(3) http://www.ncbi.nlm.nih.gov/pubmed/20828317
(4) http://www.ncbi.nlm.nih.gov/pubmed/20678009
(5) http://www.ncbi.nlm.nih.gov/pubmed/19262997
(6) http://www.ncbi.nlm.nih.gov/pubmed/19105898
(7) http://www.ncbi.nlm.nih.gov/pubmed/16823096
(8) http://www.ncbi.nlm.nih.gov/pubmed/16351512
(9) http://www.ncbi.nlm.nih.gov/pubmed/15522140
(10) http://www.ncbi.nlm.nih.gov/pubmed/14698523
Health Benefits
1. Antioxidant properties
In the investigation of the antioxidant properties of garlic compounds representing the four main chemical classes, alliin, allyl cysteine, allyl disulfide, and allicin, prepared by chemical synthesis or purification, showed that Alliin scavenged superoxide, while allyl cysteine and allyl disulfide did not react with superoxide. Allicin suppressed the formation of superoxide by the xanthine/xanthine oxidase system, probably via a thiol exchange mechanism. Alliin, allyl cysteine, and allyl disulfide all scavenged hydroxyl radicals; the rate constants calculated based on deoxyribose competitive assay were 1.4-1.7 x 10(10), 2.1-2.2 x 10(9), and 0.7-1.5 x 10(10) M (1) second(1), respectively, according to "The antioxidant properties of garlic compounds: allyl cysteine, alliin, allicin, and allyl disulfide" by Chung LY.(1)
2. Anti diabetes
In comparison of the production and therapeutic efficiency of alliin extracted from garlic leaves of plants grown under ex situ and in situ conditions, found that Alliin production noted ~50% enhancement in leaves from plants grown under in situ conditions. Serum glucose, triglycerides, total lipids, total cholesterol, low-density lipoprotein (LDL)-, and very low-density lipoprotein (VLDL)-cholesterol in diabetic rats treated with alliin produced from in situ grown plants noted significant reduction of ~54%, 15%, 14%, 20%, 24%, and 15%, while 35%, 14%, 10%, 12%, 17% and 11% reduction was noted in diabetic rats treated with alliin produced from ex situ grown plants in comparison with those administered with distilled water. High-density lipoprotein (HDL)-cholesterol did not show any significant change. Leaf extract of plants lowered serum enzyme levels (alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase) toward the norm better than glibenclamide, according to "Alliin obtained from leaf extract of garlic grown under in situ conditions possess higher therapeutic potency as analyzed in alloxan-induced diabetic rats" by Nasim SA, Dhir B, Kapoor R, Fatima S, Mahmooduzzafar, Mujib A.(2)
3. Antibacterial activity
In the investigation of an antimicrobial sulfur compound newly isolated from heated garlic extract, showed that the compound was CH₂=CH-CH₂-S-S-S-CH₂-CH(NH₂)COOH, 3-(allyltrisulfanyl)-2-aminopropanoic acid, a derivative of cysteine, presumably derived from alliin (S-allyl-L-cysteine sulfoxide). This novel compound has comparatively potent anti-yeast activity and rather weak antibacterial activity, similar to other antimicrobial compounds in garlic, according to "3-(allyltrisulfanyl)-2-aminopropanoic acid, a novel nonvolatile water-soluble antimicrobial sulfur compound in heated garlic" by Kang SS, Lim DR, Kyung KH.(3)
4. Ovarian cancer
In the investigation of a chemical conjugate between daidzein and the garlic enzyme alliinase and its effect on human ovarian cancer cells, suggest that the targeted alliinase conjugates in the presence of alliin, generated therapeutically effective levels of allicin which were capable of suppressing tumor progression of intraperitoneal ovarian cancer in an animal model, according to "Conjugates of daidzein-alliinase as a targeted pro-drug enzyme system against ovarian carcinoma" by Appel E, Rabinkov A, Neeman M, Kohen F, Mirelman D.(4)
5. Mitochondrial dysfunction
In the evaluation of the preventive role of S-allyl cysteine sulphoxide (SACS) in isoproterenol (ISO)-induced cardiotoxicity in male Wistar rats, showed that oral administration of SACS for a period of 35 days to the normal control rats did not show any significant effect. Histopathological studies of the myocardial tissue showed a protective role of SACS in the myocardial-infarcted rats. The effect at a dose of SACS 80 mg/kg was more effective than the dose 40 mg/kg. The results of the study conclude that SACS protect the mitochondria of the ISO-induced myocardial-infarcted rats, according to 'Preventive effect of S-allyl cysteine sulphoxide (Alliin) on mitochondrial dysfunction in normal and isoproterenol induced cardiotoxicity in male Wistar rats: a histopathological study" by Sangeetha T, Darlin Quine S.(5)
6. Anti-fungal efficacy
In the evaluation of the in vitro anti-fungal efficacy of the active principle of garlic, pure allicin and polybutylcyanoacrylate (PBCA) nanoparticles (NPs) loaded with allicin.
found that that pure allicin has stronger in vitro anti-fungal efficacy to six tested fungi than alliinase and alliin. Moreover, it has improved significantly after pure allicin being wrapped into PBCA NP, which may be due to the NP's good prolonged release effect and nano-scale dimensions, according to "Anti-fungal efficacy of polybutylcyanoacrylate nanoparticles of allicin and comparison with pure allicin" by Luo DQ, Guo JH, Wang FJ, Jin ZX, Cheng XL, Zhu JC, Peng CQ, Zhang C.(6)
7. Antithrombotic and anticancer effects
In the review of modern scientific research has revealed that the wide variety of dietary and medicinal functions of garlic can be attributed to the sulfur compounds present in or generated from garlic, indicated that although garlic produces more than 20 kinds of sulfide compounds from a few sulfur-containing amino acids, their functions are different from one another; e.g., allicin, methyl allyl trisulfide, and diallyl trisulfide have antibacterial, antithrombotic, and anticancer activities, respectively, according to "Antithrombotic and anticancer effects of garlic-derived sulfur compounds: a review" by Ariga T, Seki T. (7)
8. Anti-angiogenesis
In the demonstartion of dose-dependent of Alliin, a compound derived from garlic, in inhibition of fibroblast growth factor-2 (FGF2)-induced human endothelial cell (EC) tube formation and angiogenesis in the chick chorioallantoic membrane (CAM) model, showed that these data indicated a synergistic effect of antioxidants on the anti-angiogenesis and anticancer efficacy of alliin. These data also suggest the implication of cellular NO and p53 as mediators of anti-angiogenesis and anticancer effects of alliin, according to "Anti-angiogenesis efficacy of the garlic ingredient alliin and antioxidants: role of nitric oxide and p53" by Mousa AS, Mousa SA.(8)
9. Serum lipids, blood pressure and arterial stiffness
in the testing the effect of dried garlic (Allium sativum) powder on blood lipids, blood pressure and arterial stiffness in a 12-week randomised, double-blind, placebo-controlled trial. Seventy-five healthy, normo-lipidaemic volunteers (men and women aged 40-60 years) were assigned to dried garlic powder tablets (10.8 mg alliin (3-(2-propenylsulfinyl)-L-alanine)/d, corresponding to about three garlic cloves) or placebo, showed that garlic powder was associated with a near-significant decrease (12 %) in triacylglycerol concentration (P=0.07). In conclusion, garlic powder tablets have no clinically relevant lipid-lowering and blood pressure-lowering effects in middle-aged, normo-lipidaemic individuals. The putative anti-atherosclerotic effect of garlic may be linked to risk markers other than blood lipids, according to "Effect of garlic (Allium sativum) powder tablets on serum lipids, blood pressure and arterial stiffness in normo-lipidaemic volunteers: a randomised, double-blind, placebo-controlled trial" by Turner B, Mølgaard C, Marckmann P.(9)
10. Hepatoprotective effect
In the study of the interaction of the non-protein amino acid alliin with the enzyme alliinase (alliin lyase, EC 4.4.1.4). D-Galactosamine highly sensitizes the host response of the experimental animal to endotoxin (lipopolysaccharide) and causes fulminant hepatitis within 8h after administration, indicated that In D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced hepatitis rats, a significant increase of lipid peroxidation and decreased liver antioxidant enzyme levels are observed. Pretreatment with allicin, the active component of freshly crushed garlic cloves, prevented these alterations, according to "Hepatoprotective effect of allicin on tissue defense system in galactosamine/endotoxin challenged rats" by Vimal V, Devaki T.(10)
11. Etc.
Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/16822206
(2) http://www.ncbi.nlm.nih.gov/pubmed/21391887
(3) http://www.ncbi.nlm.nih.gov/pubmed/20828317
(4) http://www.ncbi.nlm.nih.gov/pubmed/20678009
(5) http://www.ncbi.nlm.nih.gov/pubmed/19262997
(6) http://www.ncbi.nlm.nih.gov/pubmed/19105898
(7) http://www.ncbi.nlm.nih.gov/pubmed/16823096
(8) http://www.ncbi.nlm.nih.gov/pubmed/16351512
(9) http://www.ncbi.nlm.nih.gov/pubmed/15522140
(10) http://www.ncbi.nlm.nih.gov/pubmed/14698523
Phytochemicals in Foods - 10 Health Benefits of Sinigrin
Sinigrin is a phytochemical glucosinolate, belongs to the family of glucosides found abundantly in Brussels sprouts, broccoli, the seeds of black mustard, etc.
Health Benefits
1. Bladder cancer
In the design of testing the hypothesis of AITC-containing cruciferous vegetables also inhibit bladder cancer development, indicated that Comparison between hydrated MSP-1 and pure sinigrin with added myrosinase suggested that the anticancer effect of MSP-1 was derived principally, if not entirely, from the AITC generated from sinigrin. In an orthotopic rat bladder cancer model, oral MSP-1 at 71.5 mg/kg (sinigrin dose of 9 μmol/kg) inhibited bladder cancer growth by 34.5% (P < 0.05) and blocked muscle invasion by 100%, according to "Allyl isothiocyanate-rich mustard seed powder inhibits bladder cancer growth and muscle invasion" by Bhattacharya A, Li Y, Wade KL, Paonessa JD, Fahey JW, Zhang Y.(1)
2. Multidirectional time-dependent effect
In a research of nutritional significance of parent glucosinolate sinigrin 50 μmol/kg b. w./day and its degradation product allyl isothiocyanate 25 μmol/kg b. w./day and 50 μmol/kg b. w./day was studied by the evaluation of their influence on some parameters of carbohydrate and lipid metabolism in an animal rat model in vivo after their single (4 h) and 2 weeks oral administration, showed that the effect of SIN and AITC is multidirectional, indicating its impact on many organs like liver as well as pancreas, intestine in vivo action and rat adipocytes in vitro. Whilst consumption of cruciferous vegetables at levels currently considered "normal" seems to be beneficial to human health, this data suggest that any large increase in intake could conceivably lead to undesirable effect, according to "Multidirectional time-dependent effect of sinigrin and allyl isothiocyanate on metabolic parameters in rats" by Okulicz M.(2)
3. Postprandial hypertriglyceridemia
In the examination of the bioactivity of Yamato-mana (Brassica rapa L. Oleifera Group) constituent glucosinolates with 3-butenyl glucosinolate (gluconapin) decreased the plasma triglyceride gain induced by corn oil administration to mice, indicated that phenethyl glucosinolate (gluconasturtiin) had little effect. 2-Propenyl glucosinolate (sinigrin) also reduced the plasma triglyceride level, which suggests that alkenyl glucosinolates might be promising agents to prevent postprandial hypertriglyceridemia, according to "Suppressive effect of Yamato-mana (Brassica rapa L. Oleifera Group) constituent 3-butenyl glucosinolate (gluconapin) on postprandial hypertriglyceridemia in mice" by Washida K, Miyata M, Koyama T, Yazawa K, Nomoto K.(3)
4. Antimicrobial effects
In the investigation of Allyl isothiocyanate (AIT) derived from the glucosinolate sinigrin found in plants of the family Brassicaceae and its antimicrobial agent against a variety of organisms, including foodborne pathogens such as Escherichia coli O157:H7, found that it can be postulated that: 1) AIT is a more effective antimicrobial at low pH values and its degradation reduces this activity; 2) decomposition products in water might not participate in the antimicrobial action of AIT; and 3) AIT seems to have a multi-targeted mechanism of action, perhaps inhibiting several metabolic pathways and damaging cellular structures, according to "Enzymatic inhibition by allyl isothiocyanate and factors affecting its antimicrobial action against Escherichia coli O157:H7" by Luciano FB, Holley RA.(4)
5. Liver cancer
In the determination of the inhibitory effects of AITC and its NAC conjugate on cell proliferation, the expression of matrix metalloproteinases (MMPs), adhesion, invasion, and migration in SK-Hep 1 human hepatoma cells, found that AITC and NAC-AITC suppress SK-Hep 1 cell proliferation in a dose-dependent manner; by 25% and 30% for 10 microM AITC and 10 microM NAC-AITC, respectively. The influence of AITC and NAC-AITC on the gene expression of MMPs and tissue inhibitors of metalloproteinase (TIMPs). Gelatin zymography also revealed a significant downregulation of MMP-2/-9 expression in SK-Hep1 cells treated with 0.1-5 microM AITC and NAC-AITC compared with controls. Reverse transcriptase polymerase chain reaction revealed dose-dependent decreases in MMP-2/-9 messenger RNA levels in both AITC-treated and NAC-AITC-treated cells, according to "Allyl isothiocyanate and its N-acetylcysteine conjugate suppress metastasis via inhibition of invasion, migration, and matrix metalloproteinase-2/-9 activities in SK-Hep 1 human hepatoma cells" by Hwang ES, Lee HJ.(5)
6. Detoxication enzymes
In the examination of the ability of allyl nitrile, a hydrolysis product of the glucosinolate sinigrin, to increase tissue levels of the phase 2 detoxication enzymes glutathione S-transferase and quinone reductase and GSH in a variety of mouse tissues, found that show that allyl nitrile displays its maximum potency in the stomach and lungs, which is of interest in light of epidemiological studies demonstrating an inverse association between crucifer intake and the incidence of stomach and lung cancers, according to "Induction of detoxication enzymes in mice by naturally occurring allyl nitrile" by Tanii H, Higashi T, Nishimura F, Higuchi Y, Saijoh K.(6)
7. Anti-SARS coronavirus 3C-like protease effects
In the study, Isatis indigotica root extract, five major compounds of I. indigotica root, and seven plant-derived phenolic compounds were tested for anti-SARS-CoV 3CLpro effects using cell-free and cell-based cleavage assays, found that Cleavage assays with the 3CLpro demonstrated that IC50 values were in micromolar ranges for I. indigotica root extract, indigo, sinigrin, aloe emodin and hesperetin. Sinigrin (IC50: 217 microM) was more efficient in blocking the cleavage processing of the 3CLpro than indigo (IC50: 752 microM) and beta-sitosterol (IC50: 1210 microM) in the cell-based assay. Only two phenolic compounds aloe emodin and hesperetin dose-dependently inhibited cleavage activity of the 3CLpro, in which the IC50 was 366 microM for aloe emodin and 8.3 microM for hesperetin in the cell-based assay, according to "Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds" by Lin CW, Tsai FJ, Tsai CH, Lai CC, Wan L, Ho TY, Hsieh CC, Chao PD.(7)
8. Colorectal cancer
In the investigation of raw juice extracted from Brussels sprouts rich in the glucosinolate sinigrin to explore the effect of naturally occurring glucosinolate breakdown products on cell cycle progression and apoptosis in human colorectal carcinoma cells (HT29), found that the main glucosinolate breakdown products were as follows: the sinigrin breakdown product, 1-cyano-2,3-epithiopropane (ca. 38 mM); the gluconapin hydrolysis product, 3-butenyl isothiocyanate (ca. 2.2.mM); the glucobrassicin metabolite, ascorbigen (ca. 8 mM); and low concentrations of other indole glucosinolate-derived hydrolysis products such as neoascorbigen and 3,3'-diindolylmethane. A variety of biologically active glucosinolate breakdown products are released by mechanical disruption of raw Brussels sprout tissue, but contrary to previous assumptions, allyl isothiocyanate is not the main compound responsible for the inhibition of cell proliferation, according to "Effects of Brussels sprout juice on the cell cycle and adhesion of human colorectal carcinoma cells (HT29) in vitro" by Smith TK, Lund EK, Clarke RG, Bennett RN, Johnson IT.(8)
9. Tumor cell proliferation and cyclooxygenase inhibitory
In the investigation of Cyclooxygenase and human tumor cell growth inhibitory from 5 compounds, namely plastoquinone-9 (1), 6-O-acyl-beta-d-glucosyl-beta-sitosterol (2), 1,2-dilinolenoyl-3-galactosylglycerol (3), linolenoyloleoyl-3-beta-galactosylglycerol (4), and 1,2-dipalmitoyl-3-beta-galactosylglycerol (5). 3-Acyl-sitosterols, sinigrin, gluconasturtiin, and phosphatidylcholines isolated from horseradish and alpha-tocopherol and ubiquinone-10 from wasabi rhizomes, showed that Compounds 3, 4, and 5 gave 75, 42, and 47% inhibition of COX-1 enzyme, respectively, at a concentration of 250 microg/mL. In a dose response study, compound 3 inhibited the proliferation of colon cancer cells (HCT-116) by 21.9, 42.9, 51.2, and 68.4% and lung cancer cells (NCI-H460) by 30, 39, 44, and 71% at concentrations of 7.5, 15, 30, and 60 microg/mL, respectively. At a concentration of 60 microg/mL, compound 4 inhibited the growth of colon, lung, and stomach cancer cells by 28, 17, and 44%, according to "Tumor cell proliferation and cyclooxygenase inhibitory constituents in horseradish (Armoracia rusticana) and Wasabi (Wasabia japonica)" by Weil MJ, Zhang Y, Nair MG.(9)
10. Antioxidants
In the examination of the effect of an aqueous extract of cooked Brussels sprouts on formation of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) in calf thymus DNA in vitro, found that Sinigrin, a glucosinolate abundant in Brussels sprouts, co-eluted with the most effective fraction and had DNA protective effects. In comparison with other antioxidants the patterns of effect of the extract in the five damage systems were more similar to that of sodium azide than to those of dimethylsulfoxide and vitamin C, according to "Inhibition of oxidative DNA damage in vitro by extracts of brussels sprouts" by Zhu C, Poulsen HE, Loft S.(10)
11. Etc.
Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/20889681
(2) http://www.ncbi.nlm.nih.gov/pubmed/20809411
(3) http://www.ncbi.nlm.nih.gov/pubmed/20530888
(4) http://www.ncbi.nlm.nih.gov/pubmed/19346022
(5) http://www.ncbi.nlm.nih.gov/pubmed/16565438
(6) http://www.ncbi.nlm.nih.gov/pubmed/16277393
(7) http://www.ncbi.nlm.nih.gov/pubmed/16115693
(8) http://www.ncbi.nlm.nih.gov/pubmed/15884814
(9) http://www.ncbi.nlm.nih.gov/pubmed/15740020
(10) http://www.ncbi.nlm.nih.gov/pubmed/10885626
Health Benefits
1. Bladder cancer
In the design of testing the hypothesis of AITC-containing cruciferous vegetables also inhibit bladder cancer development, indicated that Comparison between hydrated MSP-1 and pure sinigrin with added myrosinase suggested that the anticancer effect of MSP-1 was derived principally, if not entirely, from the AITC generated from sinigrin. In an orthotopic rat bladder cancer model, oral MSP-1 at 71.5 mg/kg (sinigrin dose of 9 μmol/kg) inhibited bladder cancer growth by 34.5% (P < 0.05) and blocked muscle invasion by 100%, according to "Allyl isothiocyanate-rich mustard seed powder inhibits bladder cancer growth and muscle invasion" by Bhattacharya A, Li Y, Wade KL, Paonessa JD, Fahey JW, Zhang Y.(1)
2. Multidirectional time-dependent effect
In a research of nutritional significance of parent glucosinolate sinigrin 50 μmol/kg b. w./day and its degradation product allyl isothiocyanate 25 μmol/kg b. w./day and 50 μmol/kg b. w./day was studied by the evaluation of their influence on some parameters of carbohydrate and lipid metabolism in an animal rat model in vivo after their single (4 h) and 2 weeks oral administration, showed that the effect of SIN and AITC is multidirectional, indicating its impact on many organs like liver as well as pancreas, intestine in vivo action and rat adipocytes in vitro. Whilst consumption of cruciferous vegetables at levels currently considered "normal" seems to be beneficial to human health, this data suggest that any large increase in intake could conceivably lead to undesirable effect, according to "Multidirectional time-dependent effect of sinigrin and allyl isothiocyanate on metabolic parameters in rats" by Okulicz M.(2)
3. Postprandial hypertriglyceridemia
In the examination of the bioactivity of Yamato-mana (Brassica rapa L. Oleifera Group) constituent glucosinolates with 3-butenyl glucosinolate (gluconapin) decreased the plasma triglyceride gain induced by corn oil administration to mice, indicated that phenethyl glucosinolate (gluconasturtiin) had little effect. 2-Propenyl glucosinolate (sinigrin) also reduced the plasma triglyceride level, which suggests that alkenyl glucosinolates might be promising agents to prevent postprandial hypertriglyceridemia, according to "Suppressive effect of Yamato-mana (Brassica rapa L. Oleifera Group) constituent 3-butenyl glucosinolate (gluconapin) on postprandial hypertriglyceridemia in mice" by Washida K, Miyata M, Koyama T, Yazawa K, Nomoto K.(3)
4. Antimicrobial effects
In the investigation of Allyl isothiocyanate (AIT) derived from the glucosinolate sinigrin found in plants of the family Brassicaceae and its antimicrobial agent against a variety of organisms, including foodborne pathogens such as Escherichia coli O157:H7, found that it can be postulated that: 1) AIT is a more effective antimicrobial at low pH values and its degradation reduces this activity; 2) decomposition products in water might not participate in the antimicrobial action of AIT; and 3) AIT seems to have a multi-targeted mechanism of action, perhaps inhibiting several metabolic pathways and damaging cellular structures, according to "Enzymatic inhibition by allyl isothiocyanate and factors affecting its antimicrobial action against Escherichia coli O157:H7" by Luciano FB, Holley RA.(4)
5. Liver cancer
In the determination of the inhibitory effects of AITC and its NAC conjugate on cell proliferation, the expression of matrix metalloproteinases (MMPs), adhesion, invasion, and migration in SK-Hep 1 human hepatoma cells, found that AITC and NAC-AITC suppress SK-Hep 1 cell proliferation in a dose-dependent manner; by 25% and 30% for 10 microM AITC and 10 microM NAC-AITC, respectively. The influence of AITC and NAC-AITC on the gene expression of MMPs and tissue inhibitors of metalloproteinase (TIMPs). Gelatin zymography also revealed a significant downregulation of MMP-2/-9 expression in SK-Hep1 cells treated with 0.1-5 microM AITC and NAC-AITC compared with controls. Reverse transcriptase polymerase chain reaction revealed dose-dependent decreases in MMP-2/-9 messenger RNA levels in both AITC-treated and NAC-AITC-treated cells, according to "Allyl isothiocyanate and its N-acetylcysteine conjugate suppress metastasis via inhibition of invasion, migration, and matrix metalloproteinase-2/-9 activities in SK-Hep 1 human hepatoma cells" by Hwang ES, Lee HJ.(5)
6. Detoxication enzymes
In the examination of the ability of allyl nitrile, a hydrolysis product of the glucosinolate sinigrin, to increase tissue levels of the phase 2 detoxication enzymes glutathione S-transferase and quinone reductase and GSH in a variety of mouse tissues, found that show that allyl nitrile displays its maximum potency in the stomach and lungs, which is of interest in light of epidemiological studies demonstrating an inverse association between crucifer intake and the incidence of stomach and lung cancers, according to "Induction of detoxication enzymes in mice by naturally occurring allyl nitrile" by Tanii H, Higashi T, Nishimura F, Higuchi Y, Saijoh K.(6)
7. Anti-SARS coronavirus 3C-like protease effects
In the study, Isatis indigotica root extract, five major compounds of I. indigotica root, and seven plant-derived phenolic compounds were tested for anti-SARS-CoV 3CLpro effects using cell-free and cell-based cleavage assays, found that Cleavage assays with the 3CLpro demonstrated that IC50 values were in micromolar ranges for I. indigotica root extract, indigo, sinigrin, aloe emodin and hesperetin. Sinigrin (IC50: 217 microM) was more efficient in blocking the cleavage processing of the 3CLpro than indigo (IC50: 752 microM) and beta-sitosterol (IC50: 1210 microM) in the cell-based assay. Only two phenolic compounds aloe emodin and hesperetin dose-dependently inhibited cleavage activity of the 3CLpro, in which the IC50 was 366 microM for aloe emodin and 8.3 microM for hesperetin in the cell-based assay, according to "Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds" by Lin CW, Tsai FJ, Tsai CH, Lai CC, Wan L, Ho TY, Hsieh CC, Chao PD.(7)
8. Colorectal cancer
In the investigation of raw juice extracted from Brussels sprouts rich in the glucosinolate sinigrin to explore the effect of naturally occurring glucosinolate breakdown products on cell cycle progression and apoptosis in human colorectal carcinoma cells (HT29), found that the main glucosinolate breakdown products were as follows: the sinigrin breakdown product, 1-cyano-2,3-epithiopropane (ca. 38 mM); the gluconapin hydrolysis product, 3-butenyl isothiocyanate (ca. 2.2.mM); the glucobrassicin metabolite, ascorbigen (ca. 8 mM); and low concentrations of other indole glucosinolate-derived hydrolysis products such as neoascorbigen and 3,3'-diindolylmethane. A variety of biologically active glucosinolate breakdown products are released by mechanical disruption of raw Brussels sprout tissue, but contrary to previous assumptions, allyl isothiocyanate is not the main compound responsible for the inhibition of cell proliferation, according to "Effects of Brussels sprout juice on the cell cycle and adhesion of human colorectal carcinoma cells (HT29) in vitro" by Smith TK, Lund EK, Clarke RG, Bennett RN, Johnson IT.(8)
9. Tumor cell proliferation and cyclooxygenase inhibitory
In the investigation of Cyclooxygenase and human tumor cell growth inhibitory from 5 compounds, namely plastoquinone-9 (1), 6-O-acyl-beta-d-glucosyl-beta-sitosterol (2), 1,2-dilinolenoyl-3-galactosylglycerol (3), linolenoyloleoyl-3-beta-galactosylglycerol (4), and 1,2-dipalmitoyl-3-beta-galactosylglycerol (5). 3-Acyl-sitosterols, sinigrin, gluconasturtiin, and phosphatidylcholines isolated from horseradish and alpha-tocopherol and ubiquinone-10 from wasabi rhizomes, showed that Compounds 3, 4, and 5 gave 75, 42, and 47% inhibition of COX-1 enzyme, respectively, at a concentration of 250 microg/mL. In a dose response study, compound 3 inhibited the proliferation of colon cancer cells (HCT-116) by 21.9, 42.9, 51.2, and 68.4% and lung cancer cells (NCI-H460) by 30, 39, 44, and 71% at concentrations of 7.5, 15, 30, and 60 microg/mL, respectively. At a concentration of 60 microg/mL, compound 4 inhibited the growth of colon, lung, and stomach cancer cells by 28, 17, and 44%, according to "Tumor cell proliferation and cyclooxygenase inhibitory constituents in horseradish (Armoracia rusticana) and Wasabi (Wasabia japonica)" by Weil MJ, Zhang Y, Nair MG.(9)
10. Antioxidants
In the examination of the effect of an aqueous extract of cooked Brussels sprouts on formation of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) in calf thymus DNA in vitro, found that Sinigrin, a glucosinolate abundant in Brussels sprouts, co-eluted with the most effective fraction and had DNA protective effects. In comparison with other antioxidants the patterns of effect of the extract in the five damage systems were more similar to that of sodium azide than to those of dimethylsulfoxide and vitamin C, according to "Inhibition of oxidative DNA damage in vitro by extracts of brussels sprouts" by Zhu C, Poulsen HE, Loft S.(10)
11. Etc.
Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/20889681
(2) http://www.ncbi.nlm.nih.gov/pubmed/20809411
(3) http://www.ncbi.nlm.nih.gov/pubmed/20530888
(4) http://www.ncbi.nlm.nih.gov/pubmed/19346022
(5) http://www.ncbi.nlm.nih.gov/pubmed/16565438
(6) http://www.ncbi.nlm.nih.gov/pubmed/16277393
(7) http://www.ncbi.nlm.nih.gov/pubmed/16115693
(8) http://www.ncbi.nlm.nih.gov/pubmed/15884814
(9) http://www.ncbi.nlm.nih.gov/pubmed/15740020
(10) http://www.ncbi.nlm.nih.gov/pubmed/10885626
Phytochemicals in Foods - 11 Health Benefits of 3,3'-Diindolylmethane
3,3'-Diindolylmethane or DIM are phytochemicals derived from the digestion of indole-3-carbinol, belonging to the group of Indoles, found abundantly in broccoli, Brussels sprouts, cabbage and kale, etc.
Health Benefits
1. Antiinflammatory and chemopreventive effects on Skin
In the examination of the effects of 3,3'-Diindolylmethane (DIM) on antiinflammatory and antitumor promotion activity in mouse skin and explored the relevant mechanism, indicated that Several lead compounds, such as genistein (from soybeans), lycopene (from tomatoes), brassinin (from cruciferous vegetables), sulforaphane (from asparagus), indole-3-carbinol (from broccoli), and resveratrol (from grapes and peanuts) are in preclinical or clinical trials for cancer chemoprevention. Phytochemicals have great potential in cancer prevention because of their safety, low cost, and oral bioavailability. In this review, we discuss potential natural cancer preventive compounds and their mechanisms of action, according to "3,3'-diindolylmethane suppresses 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and tumor promotion in mouse skin via the downregulation of inflammatory mediators" by Kim EJ, Park H, Kim J, Park JH.(1)
2. Antileukemic Activity
In the study of 3,3'-diindolylmethane (DIM), one of the active products derived from Brassica plants, for it antitumor effects, showed that DIM significantly induced apoptosis in U937 human leukemia cells in dose- and time-dependent manners. These events were also noted in other human leukemia cells (Jurkat and HL-60) and primary human leukemia cells (AML) but not in normal bone marrow mononuclear cells. DIM-induced lethality is associated with caspases activation, myeloid cell leukemia-1 (Mcl-1) down-regulation, p21(cip1/waf1) up-regulation, and Akt inactivation accompanied by c-jun NH2-terminal kinase (JNK) activation. Enforced activation of Akt by a constitutively active Akt construct prevented DIM-mediated caspase activation, Mcl-1 down-regulation, JNK activation, and apoptosis, according to "3, 3'-Diindolylmethane Exhibits Antileukemic Activity In Vitro and In Vivo through a Akt-Dependent Process" by Gao N, Cheng S, Budhraja A, Liu EH, Chen J, Chen D, Yang Z, Luo J, Shi X, Zhang Z.(2)
3. Cervical Cancer
In the examination of 3,3'-Diindolylmethane (DIM) prevention or inhibition of the progression from cervical dysplasia to Human papilloma viral causes of cervical neoplasia (CIN), found that significant increases in IFN-γ serum concentrations that correlate with the percentage of CIN free mice in each group indicate that 1000 ppm of DIM in food may be the most effective dose for future studies. These results may eventually lead to new and effective vaccination strategies in women already infected with the human papilloma virus, according to '3,3'-Diindolylmethane Increases Serum Interferon-γ Levels in the K14-HPV16 Transgenic Mouse Model for Cervical Cancer" by Sepkovic DW, Raucci L, Stein J, Carlisle AD, Auborn K, Ksieski HB, Nyirenda T, Bradlow HL.(3)
4. Esophageal cancer
In the study of 3,3'-Diindolylmethane (DIM), an active metabolite of indole-3-carbinol, and its antitumor effects in experimental animals and induction of apoptosis in various cancer cells, showed that DIM significantly inhibited the proliferation of ESCC cells in a dose- and time-dependent manner. The percentage of G1 phase cells increased 48 h after being treated with DIM. DIM also reduced cyclin D1, cyclin E2, cyclin-dependent kinase (CDK) 4 and CDK 6 activities, and increased p15 and p27 levels. Additionally, DIM diminished pro-caspase-9 protein expression levels and induced increased cleaved poly (ADP-ribose) polymerase levels, accoridng to "3,3'-Diindolylmethane suppresses growth of human esophageal squamous cancer cells by G1 cell cycle arrest"by Kim SJ, Lee JS, Kim SM.(4)
5. Prostate cancer
In the stuidy of whether DIM inhibits the development of prostate cancer using the transgenic adenocarcinoma mouse prostate (TRAMP) model, showed that DIM induced a substantial reduction in the numbers of viable cells and induced apoptosis in LNCaP and DU145 cells. DIM increased the cleavage of caspase-9, -7, -3, and poly (ADP-ribose) polymerase (PARP). DIM increased mitochondrial membrane permeability and the translocation of cytochrome c and Smac/Diablo from the mitochondria. Additionally, DIM induced increases in the levels of cleaved caspase-8, truncated Bid, Fas, and Fas ligand, and the caspase-8 inhibitor Z-IETD-FMK was shown to mitigate DIM-induced apoptosis and the cleavage of caspase-3, PARP, and Bid, according to '3,3'-Diindolylmethane inhibits prostate cancer development in the transgenic adenocarcinoma mouse prostate model" by Cho HJ, Park SY, Kim EJ, Kim JK, Park JH.(5)
6. Oral Cancer
In the investigation of the antitumor activity of 3,3'-diindolylmethane (DIM), an active metabolite of the phytochemical indole-3-carbinol (I3C), in oral squamous cell carcinoma (OSCC), showed that DIM stimulated the activation of p53 via Ser-15 phosphorylation, leading to increased expression of the BH3-only proapoptotic Bcl-2 members Puma and Noxa. Together, these changes decreased the mitochondrial threshold for apoptosis. G2/M arrest might be attributable to the suppressive effect of DIM on the expression of cyclin B1 and cdc25c. As many downstream effectors of the Akt-NF-κB pathway, including glycogen synthase kinase 3β, IκB kinase α, and cyclooxygenase-2, have been shown to promote oral tumorigenesis, the ability of DIM to inhibit this signaling axis underscores its chemopreventive potential in oral cancer, according to "The dietary phytochemical 3,3'-diindolylmethane induces G2/M arrest and apoptosis in oral squamous cell carcinoma by modulating Akt-NF-κB, MAPK, and p53 signaling" by Weng JR, Bai LY, Chiu CF, Wang YC, Tsai MH.(6)
7. Ovarian cancer
In the delineation of the mechanism by which DIM suppressed the growth of SKOV3, OVCAR-3 and TOV-21G human ovarian cancer cells, found that DIM treatment also inhibited the kinase activity of ERK as observed by the down regulation of p-ELK in all the three ovarian cancer cell lines. DIM significantly suppressed the growth of ovarian tumors in vivo. Tumor growth suppressive effects of DIM in SKOV-3 tumor xenografts were associated with reduced phosphorylation of EGFR, MEK and ERK, according to "Blocking EGFR activation suppresses ovarian tumor growth in vitro and in vivo" by Kandala PK, Wright SE, Srivastava SK.(7)
8. Colon cancer
In the analyzing the expression pattern of N-myc downstream regulated gene-1 following treatment of human colonic cancer cell lines, suggested that N-myc downstream regulated gene-1 expression is enhanced by 3,3'-diindolylmethane in poorly differentiated cells and followed by induction of apoptosis. 3,3'-diindolylmethane induced apoptosis may represent a new regulator of N-myc downstream regulated gene-1 in poorly differentiated colonic cancer cells, according to "The indolic diet-derivative, 3,3'-diindolylmethane, induced apoptosis in human colon cancer cells through upregulation of NDRG1" by Lerner A, Grafi-Cohen M, Napso T, Azzam N, Fares F.(8)
9. Osteosarcoma
In the investigation of the effect of the natural product 3,3'-diindolylmethane (DIM) on cytosolic Ca(2+) concentrations ([Ca(2+) ](i) ) and viability in MG63 human osteosarcoma cells, found that DIM-evoked Ca(2+) entry was suppressed by nifedipine, econazole, SK&F96365 and protein kinase C modulators. In the absence of extracellular Ca(2+) , incubation with the endoplasmic reticulum Ca(2+) pump inhibitors thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) inhibited or abolished DIM-induced [Ca(2+) ](i) rise. Incubation with DIM also inhibited thapsigargin or BHQ-induced [Ca(2+) ](i) rise. Inhibition of phospholipase C with U73122 abolished DIM-induced [Ca(2+) ](i) rise. At concentrations of 10-50 μM, DIM killed cells in a concentration-dependent manner, according to "3,3'-Diindolylmethane Alters Ca(2+) Homeostasis and Viability in MG63 Human Osteosarcoma Cells" by Lu YC, Chen IS, Chou CT, Huang JK, Chang HT, Tsai JY, Hsu SS, Liao WC, Wang JL, Lin KL, Liu SI, Kuo CC, Ho CM, Jan CR.(9)
10. Breast cancer
in the assessment of the effects of DIM on cell-cycle regulation in both estrogen-dependent MCF-7 and estrogen receptor negative p53 mutant MDA-MB-468 human breast cancer cells,
showed that DIM inhibited the breast cancer cell growth in vitro and in vivo, and caused cell-cycle arrest by down-regulating protein levels of cell-cycle related kinases CDK1, CDK2, CDK4, and CDK6, as well as Cyclin B1 and Cdc25A. Meanwhile, it was revealed that Ser(124) phosphorylation of Cdc25A is primarily responsible for the DIM-induced Cdc25A degradation. Furthermore, treatment of MCF-7 cells with DIM increased miR-21 expression and down-regulated Cdc25A, resulting in an inhibition of breast cancer cell proliferation, according to " 3,3'-Diindolylmethane inhibits breast cancer cell growth via miR-21-mediated Cdc25A degradation' by Jin Y.(10)
11. Thyroid cancer
In the investigation of the property of a natural dietary compound found in cruciferous vegetables, 3,3'-diindolylmethane (DIM), to target the metastatic phenotype of thyroid cancer cells through a functional estrogen receptor, found that DIM inhibits estrogen mediated increase in thyroid cell migration, adhesion and invasion, which is also supported by ER-α downregulation (siRNA) studies. Western blot and zymography analyses provided direct evidence for this DIM mediated inhibition of E(2) enhanced metastasis associated events by virtue of targeting essential proteolytic enzymes, namely MMP-2 and MMP-9, according to "Estrogen induced metastatic modulators MMP-2 and MMP-9 are targets of 3,3'-diindolylmethane in thyroid cancer' by Rajoria S, Suriano R, George A, Shanmugam A, Schantz SP, Geliebter J, Tiwari RK.(11)
12. Etc.
Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/20564344
(2) http://www.ncbi.nlm.nih.gov/pubmed/22363731
(3) http://www.ncbi.nlm.nih.gov/pubmed/22351660
(4) http://www.ncbi.nlm.nih.gov/pubmed/22293900
(5) http://www.ncbi.nlm.nih.gov/pubmed/21229607
(6) http://www.ncbi.nlm.nih.gov/pubmed/22290291
(7) http://www.ncbi.nlm.nih.gov/pubmed/22205686
(8) http://www.ncbi.nlm.nih.gov/pubmed/22187533
(9) http://www.ncbi.nlm.nih.gov/pubmed/21995587
(10) http://www.ncbi.nlm.nih.gov/pubmed/21761201
(11) http://www.ncbi.nlm.nih.gov/pubmed/21267453
Health Benefits
1. Antiinflammatory and chemopreventive effects on Skin
In the examination of the effects of 3,3'-Diindolylmethane (DIM) on antiinflammatory and antitumor promotion activity in mouse skin and explored the relevant mechanism, indicated that Several lead compounds, such as genistein (from soybeans), lycopene (from tomatoes), brassinin (from cruciferous vegetables), sulforaphane (from asparagus), indole-3-carbinol (from broccoli), and resveratrol (from grapes and peanuts) are in preclinical or clinical trials for cancer chemoprevention. Phytochemicals have great potential in cancer prevention because of their safety, low cost, and oral bioavailability. In this review, we discuss potential natural cancer preventive compounds and their mechanisms of action, according to "3,3'-diindolylmethane suppresses 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and tumor promotion in mouse skin via the downregulation of inflammatory mediators" by Kim EJ, Park H, Kim J, Park JH.(1)
2. Antileukemic Activity
In the study of 3,3'-diindolylmethane (DIM), one of the active products derived from Brassica plants, for it antitumor effects, showed that DIM significantly induced apoptosis in U937 human leukemia cells in dose- and time-dependent manners. These events were also noted in other human leukemia cells (Jurkat and HL-60) and primary human leukemia cells (AML) but not in normal bone marrow mononuclear cells. DIM-induced lethality is associated with caspases activation, myeloid cell leukemia-1 (Mcl-1) down-regulation, p21(cip1/waf1) up-regulation, and Akt inactivation accompanied by c-jun NH2-terminal kinase (JNK) activation. Enforced activation of Akt by a constitutively active Akt construct prevented DIM-mediated caspase activation, Mcl-1 down-regulation, JNK activation, and apoptosis, according to "3, 3'-Diindolylmethane Exhibits Antileukemic Activity In Vitro and In Vivo through a Akt-Dependent Process" by Gao N, Cheng S, Budhraja A, Liu EH, Chen J, Chen D, Yang Z, Luo J, Shi X, Zhang Z.(2)
3. Cervical Cancer
In the examination of 3,3'-Diindolylmethane (DIM) prevention or inhibition of the progression from cervical dysplasia to Human papilloma viral causes of cervical neoplasia (CIN), found that significant increases in IFN-γ serum concentrations that correlate with the percentage of CIN free mice in each group indicate that 1000 ppm of DIM in food may be the most effective dose for future studies. These results may eventually lead to new and effective vaccination strategies in women already infected with the human papilloma virus, according to '3,3'-Diindolylmethane Increases Serum Interferon-γ Levels in the K14-HPV16 Transgenic Mouse Model for Cervical Cancer" by Sepkovic DW, Raucci L, Stein J, Carlisle AD, Auborn K, Ksieski HB, Nyirenda T, Bradlow HL.(3)
4. Esophageal cancer
In the study of 3,3'-Diindolylmethane (DIM), an active metabolite of indole-3-carbinol, and its antitumor effects in experimental animals and induction of apoptosis in various cancer cells, showed that DIM significantly inhibited the proliferation of ESCC cells in a dose- and time-dependent manner. The percentage of G1 phase cells increased 48 h after being treated with DIM. DIM also reduced cyclin D1, cyclin E2, cyclin-dependent kinase (CDK) 4 and CDK 6 activities, and increased p15 and p27 levels. Additionally, DIM diminished pro-caspase-9 protein expression levels and induced increased cleaved poly (ADP-ribose) polymerase levels, accoridng to "3,3'-Diindolylmethane suppresses growth of human esophageal squamous cancer cells by G1 cell cycle arrest"by Kim SJ, Lee JS, Kim SM.(4)
5. Prostate cancer
In the stuidy of whether DIM inhibits the development of prostate cancer using the transgenic adenocarcinoma mouse prostate (TRAMP) model, showed that DIM induced a substantial reduction in the numbers of viable cells and induced apoptosis in LNCaP and DU145 cells. DIM increased the cleavage of caspase-9, -7, -3, and poly (ADP-ribose) polymerase (PARP). DIM increased mitochondrial membrane permeability and the translocation of cytochrome c and Smac/Diablo from the mitochondria. Additionally, DIM induced increases in the levels of cleaved caspase-8, truncated Bid, Fas, and Fas ligand, and the caspase-8 inhibitor Z-IETD-FMK was shown to mitigate DIM-induced apoptosis and the cleavage of caspase-3, PARP, and Bid, according to '3,3'-Diindolylmethane inhibits prostate cancer development in the transgenic adenocarcinoma mouse prostate model" by Cho HJ, Park SY, Kim EJ, Kim JK, Park JH.(5)
6. Oral Cancer
In the investigation of the antitumor activity of 3,3'-diindolylmethane (DIM), an active metabolite of the phytochemical indole-3-carbinol (I3C), in oral squamous cell carcinoma (OSCC), showed that DIM stimulated the activation of p53 via Ser-15 phosphorylation, leading to increased expression of the BH3-only proapoptotic Bcl-2 members Puma and Noxa. Together, these changes decreased the mitochondrial threshold for apoptosis. G2/M arrest might be attributable to the suppressive effect of DIM on the expression of cyclin B1 and cdc25c. As many downstream effectors of the Akt-NF-κB pathway, including glycogen synthase kinase 3β, IκB kinase α, and cyclooxygenase-2, have been shown to promote oral tumorigenesis, the ability of DIM to inhibit this signaling axis underscores its chemopreventive potential in oral cancer, according to "The dietary phytochemical 3,3'-diindolylmethane induces G2/M arrest and apoptosis in oral squamous cell carcinoma by modulating Akt-NF-κB, MAPK, and p53 signaling" by Weng JR, Bai LY, Chiu CF, Wang YC, Tsai MH.(6)
7. Ovarian cancer
In the delineation of the mechanism by which DIM suppressed the growth of SKOV3, OVCAR-3 and TOV-21G human ovarian cancer cells, found that DIM treatment also inhibited the kinase activity of ERK as observed by the down regulation of p-ELK in all the three ovarian cancer cell lines. DIM significantly suppressed the growth of ovarian tumors in vivo. Tumor growth suppressive effects of DIM in SKOV-3 tumor xenografts were associated with reduced phosphorylation of EGFR, MEK and ERK, according to "Blocking EGFR activation suppresses ovarian tumor growth in vitro and in vivo" by Kandala PK, Wright SE, Srivastava SK.(7)
8. Colon cancer
In the analyzing the expression pattern of N-myc downstream regulated gene-1 following treatment of human colonic cancer cell lines, suggested that N-myc downstream regulated gene-1 expression is enhanced by 3,3'-diindolylmethane in poorly differentiated cells and followed by induction of apoptosis. 3,3'-diindolylmethane induced apoptosis may represent a new regulator of N-myc downstream regulated gene-1 in poorly differentiated colonic cancer cells, according to "The indolic diet-derivative, 3,3'-diindolylmethane, induced apoptosis in human colon cancer cells through upregulation of NDRG1" by Lerner A, Grafi-Cohen M, Napso T, Azzam N, Fares F.(8)
9. Osteosarcoma
In the investigation of the effect of the natural product 3,3'-diindolylmethane (DIM) on cytosolic Ca(2+) concentrations ([Ca(2+) ](i) ) and viability in MG63 human osteosarcoma cells, found that DIM-evoked Ca(2+) entry was suppressed by nifedipine, econazole, SK&F96365 and protein kinase C modulators. In the absence of extracellular Ca(2+) , incubation with the endoplasmic reticulum Ca(2+) pump inhibitors thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) inhibited or abolished DIM-induced [Ca(2+) ](i) rise. Incubation with DIM also inhibited thapsigargin or BHQ-induced [Ca(2+) ](i) rise. Inhibition of phospholipase C with U73122 abolished DIM-induced [Ca(2+) ](i) rise. At concentrations of 10-50 μM, DIM killed cells in a concentration-dependent manner, according to "3,3'-Diindolylmethane Alters Ca(2+) Homeostasis and Viability in MG63 Human Osteosarcoma Cells" by Lu YC, Chen IS, Chou CT, Huang JK, Chang HT, Tsai JY, Hsu SS, Liao WC, Wang JL, Lin KL, Liu SI, Kuo CC, Ho CM, Jan CR.(9)
10. Breast cancer
in the assessment of the effects of DIM on cell-cycle regulation in both estrogen-dependent MCF-7 and estrogen receptor negative p53 mutant MDA-MB-468 human breast cancer cells,
showed that DIM inhibited the breast cancer cell growth in vitro and in vivo, and caused cell-cycle arrest by down-regulating protein levels of cell-cycle related kinases CDK1, CDK2, CDK4, and CDK6, as well as Cyclin B1 and Cdc25A. Meanwhile, it was revealed that Ser(124) phosphorylation of Cdc25A is primarily responsible for the DIM-induced Cdc25A degradation. Furthermore, treatment of MCF-7 cells with DIM increased miR-21 expression and down-regulated Cdc25A, resulting in an inhibition of breast cancer cell proliferation, according to " 3,3'-Diindolylmethane inhibits breast cancer cell growth via miR-21-mediated Cdc25A degradation' by Jin Y.(10)
11. Thyroid cancer
In the investigation of the property of a natural dietary compound found in cruciferous vegetables, 3,3'-diindolylmethane (DIM), to target the metastatic phenotype of thyroid cancer cells through a functional estrogen receptor, found that DIM inhibits estrogen mediated increase in thyroid cell migration, adhesion and invasion, which is also supported by ER-α downregulation (siRNA) studies. Western blot and zymography analyses provided direct evidence for this DIM mediated inhibition of E(2) enhanced metastasis associated events by virtue of targeting essential proteolytic enzymes, namely MMP-2 and MMP-9, according to "Estrogen induced metastatic modulators MMP-2 and MMP-9 are targets of 3,3'-diindolylmethane in thyroid cancer' by Rajoria S, Suriano R, George A, Shanmugam A, Schantz SP, Geliebter J, Tiwari RK.(11)
12. Etc.
Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/20564344
(2) http://www.ncbi.nlm.nih.gov/pubmed/22363731
(3) http://www.ncbi.nlm.nih.gov/pubmed/22351660
(4) http://www.ncbi.nlm.nih.gov/pubmed/22293900
(5) http://www.ncbi.nlm.nih.gov/pubmed/21229607
(6) http://www.ncbi.nlm.nih.gov/pubmed/22290291
(7) http://www.ncbi.nlm.nih.gov/pubmed/22205686
(8) http://www.ncbi.nlm.nih.gov/pubmed/22187533
(9) http://www.ncbi.nlm.nih.gov/pubmed/21995587
(10) http://www.ncbi.nlm.nih.gov/pubmed/21761201
(11) http://www.ncbi.nlm.nih.gov/pubmed/21267453
Phytochemicals in Foods - 10 Health Benefits of Indole-3-carbinol
Indole-3-carbinol is a phytochemical in the class of Indoles, found abundantly in cabbage, kale, brussels sprouts, rutabaga, mustard greens, broccoli, etc.
Health Benefits
1. Breast cancer
In the investigation of treatment of highly tumorigenic MDA-MB-231 human breast cancer cells with indole-3-carbinol (I3C) directly inhibited the extracellular elastase-dependent cleavage of membrane-associated CD40, showed that I3C directly inhibits the elastase-mediated proteolytic processing of CD40, which alters downstream signaling to disrupt NF-kappaB-induced cell survival and proliferative responses. Furthermore, the establish of a new I3C-mediated antiproliferative cascade has significant therapeutic potential for treatment of human cancers associated with high levels of elastase and its CD40 membrane substrate, according to "Direct inhibition of elastase activity by indole-3-carbinol triggers a CD40-TRAF regulatory cascade that disrupts NF-kappaB transcriptional activity in human breast cancer cells" by Aronchik I, Bjeldanes LF, Firestone GL.(1)
2. Lung cancer
In the examination of the inhibitory effects of N-acetyl-S-(N-2-phenethylthiocarbamoyl)-l-cysteine (PEITC-NAC), myo-inositol (MI) and indole-3-carbinol (I3C) or 3,3'-diindolylmethane (DIM), alone and in combination, on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) plus benzo[a]pyrene (BaP)-induced A/J mouse lung tumorigenesis and proliferation of A549 cells and human bronchial epithelial cells (HBECs) and relevant potential mechanisms, found that the assessment of the anti-proliferative effects of the individual agents or their combinations showed significant reductions in the proliferation of cigarette smoke condensate (CSC)-pretreated HBEC (reduction by 30-41% at 48 h and 41-58% at 72 h) and A549 cells (30-43% at 48 h and 40-59% at 72 h), but not in dimethyl sulfoxide-pretreated HBEC. Combinatorial treatment with the agents also caused marked reductions in the activation of Akt, extracellular signal-regulated kinase and nuclear factor-kappaB in lung tumor tissues, CSC-pretreated HBEC and A549 cells, according to "Inhibition of lung carcinogenesis and critical cancer-related signaling pathways by N-acetyl-S-(N-2-phenethylthiocarbamoyl)-l-cysteine, indole-3-carbinol and myo-inositol, alone and in combination" by Kassie F, Melkamu T, Endalew A, Upadhyaya P, Luo X, Hecht SS.(2)
3. Pancreatic cell lines
In the examination of the possible mechanism of I3C-enhanced efficacy on pancreatic cell lines (BxPC-3, Mia Paca-2, PL-45, AsPC-1 and PANC-1) for modulation of human equilibrative nucleoside transporter 1 (hENT1) expression, showed that Gemcitabine alone showed no effect on hENT1 expression. However, combining gemcitabine with I3C further increased hENT1 expression. Cell viability assays revealed no effect of I3C on normal cells, hTERT-HPNE. hENT1-specific inhibitor, nitrobenzylthioinosine, significantly abrogated I3C-induced gemcitabine cytotoxicity, further demonstrating its specificity, according to "Enhanced efficacy of gemcitabine by indole-3-carbinol in pancreatic cell lines: the role of human equilibrative nucleoside transporter 1" by Wang H, Word BR, Lyn-Cook BD.(3)
4. Prostate cancer
In the examination of the chemopreventive effects and the molecular mechanism of I3C, particularly the anti-oxidative stress pathway regulated by nuclear erythroid related factor 2 (Nrf2), found that treatments of transgenic adenocarcinoma of mouse prostate, TRAMP C1 cells with I3C also resulted in the induction of Nrf2-mediated genes. I3C significantly suppressed the incidence of palpable tumor and reduced the genitourinary weight in TRAMP mice. Western blots and qPCR analyses of prostate tissues showed that I3C induced the expression of Nrf2, NAD(P)H quinine oxidoreductase 1 (NQO-1) as well as cell cycle and apoptosis related biomarkers in I3C-fed TRAMP mice, according to "In vivo pharmacodynamics of indole-3-carbinol in the inhibition of prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) mice: Involvement of Nrf2 and cell cycle/apoptosis signaling pathways" by Wu TY, Saw CL, Khor TO, Pung D, Boyanapalli SS, Kong AN.(4)
5. Vulval intraepithelial neoplasia
In the evaluation of the effectiveness and safety of medical interventions for high grade Vulval intraepithelial neoplasia (VIN), a pre-malignant condition of the vulval skin, associated with infection with human papilloma virus (HPV) infection, indicated that four trials met our inclusion criteria: three assessed the effectiveness of topical imiquimod versus placebo in women with high grade VIN; one examined low versus high dose indole-3-carbinol in similar women. Meta-analysis of three trials found that the proportion of women who responded to treatment at 5 to 6 months was much higher in the group who received topical imiquimod than in the group who received placebo (relative risk (RR) = 11.95, 95% confidence interval (CI) 3.21 to 44.51), according to "Medical interventions for high grade vulval intraepithelial neoplasia" by Pepas L, Kaushik S, Bryant A, Nordin A, Dickinson HO.(5)
6. Estrogen Metabolism
In the investigation of determine whether a breast health supplement containing indole-3-carbinol and hydroxymatairesinol lignan would alter estrogen metabolism to favour C-2 hydroxylation and reduce C-16 hydroxylation, found that Supplementation with a mixture of indole-3-carbinol and HMR lignan in women significantly increased estrogen C-2 hydroxylation. This may constitute a mechanism for the reduction of breast cancer risk as well as risk for other estrogen-related cancers. Further studies with higher numbers of subjects are indicated, according to "Effects of A Breast-Health Herbal Formula Supplement on Estrogen Metabolism in Pre- and Post-Menopausal Women not Taking Hormonal Contraceptives or Supplements: A Randomized Controlled Trial" by Laidlaw M, Cockerline CA, Sepkovic DW.(6)
7. Oral cancer
In the investigation ofthe antitumor effects of OSU-A9, a structurally optimized I3C derivative, in a panel of oral squamous cell carcinoma cell lines, SCC4, SCC15, and SCC2095, showed that The antiproliferative effect of OSU-A9 was approximately two-orders-of-magnitude higher than that of I3C. Importantly, normal human oral keratinocytes were less sensitive to OSU-A9 than oral cancer cells. This antiproliferative effect of OSU-A9 was attributable to the induction of mitochondrial-dependent apoptosis as evidenced by sub-G1 accumulation of cells, poly ADP-ribose polymerase cleavage, and cytochrome c release from the mitochondria. OSU-A9 down regulates Akt and NF-κB signaling pathways, leading to changes in many downstream effectors involved in regulating cell cycle and apoptosis, according to "A novel indole-3-carbinol derivative inhibits the growth of human oral squamous cell carcinoma in vitro" by Weng JR, Bai LY, Omar HA, Sargeant AM, Yeh CT, Chen YY, Tsai MH, Chiu CF.(7)
8. Cancer prevention
In the review of botanical and nutritional compounds have been used for the treatment of cancer throughout history, indicated that several lead compounds, such as genistein (from soybeans), lycopene (from tomatoes), brassinin (from cruciferous vegetables), sulforaphane (from asparagus), indole-3-carbinol (from broccoli), and resveratrol (from grapes and peanuts) are in preclinical or clinical trials for cancer chemoprevention. Phytochemicals have great potential in cancer prevention because of their safety, low cost, and oral bioavailability, according to "Cancer prevention with natural compounds" by Gullett NP, Ruhul Amin AR, Bayraktar S, Pezzuto JM, Shin DM, Khuri FR, Aggarwal BB, Surh YJ, Kucuk O.(8)
9. Nasopharyngeal cancer
In the examination of the apoptotic effects of indole-3-carbinol (I3C) in many human cancer cells, found that Treatment with I3C significantly suppressed XIAP, c-IAP1 and Survivin protein, while elevated the expression of Omi, Smac and Cyto-c. Fas/FasL and MAPK pathway were involved in the induction of apoptosis. Taken together, these results demonstrated that I3C may induce mitochondria-mediated apoptosis via the Fas death receptor in CNE-2 cells. This molecular mechanism for apoptotic effect of I3C on nasopharyngeal cancer cells suggested that I3C might become a preventive and therapeutic agent against nasopharyngeal cancer, according to "Indole-3-carbinol (I3C)-induced apoptosis in nasopharyngeal cancer cells through Fas/FasL and MAPK pathway" by Xu Y, Zhang J, Dong WG.(9)
10. Colon cancer
In an easy two-step synthesis for 4-methoxyindole-3-carbinol (4MeOI3C), the expected breakdown product of 4-methoxyglucobrassicin during ingestion. 4MeOI3C inhibited the proliferation of human colon cancer cells DLD-1 and HCT 116 with IC(50) values of 116 microM and 96 microM, respectively, found that after 48 h in vitro, and is therefore a more potent inhibitor than indole-3-carbinol (I3C). 4MeOI3C and I3C combined in different molar ratios inhibited proliferation in a nearly additive to slightly synergistic manner. Proliferation was inhibited by 100 microM 4MeOI3C after 48 h without affecting cell cycle phase distribution, indicating an overall-slowdown effect on the cell cycle, according to "Effect of 4-methoxyindole-3-carbinol on the proliferation of colon cancer cells in vitro, when treated alone or in combination with indole-3-carbinol" by Kronbak R, Duus F, Vang O.(10)
11. Etc.
(1) http://www.ncbi.nlm.nih.gov/pubmed/20530686
(2) http://www.ncbi.nlm.nih.gov/pubmed/20603442
(3) http://www.ncbi.nlm.nih.gov/pubmed/21965724
(4) http://www.ncbi.nlm.nih.gov/pubmed/21837756
(5) http://www.ncbi.nlm.nih.gov/pubmed/21491403
(6) http://www.ncbi.nlm.nih.gov/pubmed/21234288
(7) http://www.ncbi.nlm.nih.gov/pubmed/20843730
(8) http://www.ncbi.nlm.nih.gov/pubmed/20709209
(9) http://www.ncbi.nlm.nih.gov/pubmed/20628834
(10) http://pubs.acs.org/doi/abs/10.1021/jf101806t
Health Benefits
1. Breast cancer
In the investigation of treatment of highly tumorigenic MDA-MB-231 human breast cancer cells with indole-3-carbinol (I3C) directly inhibited the extracellular elastase-dependent cleavage of membrane-associated CD40, showed that I3C directly inhibits the elastase-mediated proteolytic processing of CD40, which alters downstream signaling to disrupt NF-kappaB-induced cell survival and proliferative responses. Furthermore, the establish of a new I3C-mediated antiproliferative cascade has significant therapeutic potential for treatment of human cancers associated with high levels of elastase and its CD40 membrane substrate, according to "Direct inhibition of elastase activity by indole-3-carbinol triggers a CD40-TRAF regulatory cascade that disrupts NF-kappaB transcriptional activity in human breast cancer cells" by Aronchik I, Bjeldanes LF, Firestone GL.(1)
2. Lung cancer
In the examination of the inhibitory effects of N-acetyl-S-(N-2-phenethylthiocarbamoyl)-l-cysteine (PEITC-NAC), myo-inositol (MI) and indole-3-carbinol (I3C) or 3,3'-diindolylmethane (DIM), alone and in combination, on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) plus benzo[a]pyrene (BaP)-induced A/J mouse lung tumorigenesis and proliferation of A549 cells and human bronchial epithelial cells (HBECs) and relevant potential mechanisms, found that the assessment of the anti-proliferative effects of the individual agents or their combinations showed significant reductions in the proliferation of cigarette smoke condensate (CSC)-pretreated HBEC (reduction by 30-41% at 48 h and 41-58% at 72 h) and A549 cells (30-43% at 48 h and 40-59% at 72 h), but not in dimethyl sulfoxide-pretreated HBEC. Combinatorial treatment with the agents also caused marked reductions in the activation of Akt, extracellular signal-regulated kinase and nuclear factor-kappaB in lung tumor tissues, CSC-pretreated HBEC and A549 cells, according to "Inhibition of lung carcinogenesis and critical cancer-related signaling pathways by N-acetyl-S-(N-2-phenethylthiocarbamoyl)-l-cysteine, indole-3-carbinol and myo-inositol, alone and in combination" by Kassie F, Melkamu T, Endalew A, Upadhyaya P, Luo X, Hecht SS.(2)
3. Pancreatic cell lines
In the examination of the possible mechanism of I3C-enhanced efficacy on pancreatic cell lines (BxPC-3, Mia Paca-2, PL-45, AsPC-1 and PANC-1) for modulation of human equilibrative nucleoside transporter 1 (hENT1) expression, showed that Gemcitabine alone showed no effect on hENT1 expression. However, combining gemcitabine with I3C further increased hENT1 expression. Cell viability assays revealed no effect of I3C on normal cells, hTERT-HPNE. hENT1-specific inhibitor, nitrobenzylthioinosine, significantly abrogated I3C-induced gemcitabine cytotoxicity, further demonstrating its specificity, according to "Enhanced efficacy of gemcitabine by indole-3-carbinol in pancreatic cell lines: the role of human equilibrative nucleoside transporter 1" by Wang H, Word BR, Lyn-Cook BD.(3)
4. Prostate cancer
In the examination of the chemopreventive effects and the molecular mechanism of I3C, particularly the anti-oxidative stress pathway regulated by nuclear erythroid related factor 2 (Nrf2), found that treatments of transgenic adenocarcinoma of mouse prostate, TRAMP C1 cells with I3C also resulted in the induction of Nrf2-mediated genes. I3C significantly suppressed the incidence of palpable tumor and reduced the genitourinary weight in TRAMP mice. Western blots and qPCR analyses of prostate tissues showed that I3C induced the expression of Nrf2, NAD(P)H quinine oxidoreductase 1 (NQO-1) as well as cell cycle and apoptosis related biomarkers in I3C-fed TRAMP mice, according to "In vivo pharmacodynamics of indole-3-carbinol in the inhibition of prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) mice: Involvement of Nrf2 and cell cycle/apoptosis signaling pathways" by Wu TY, Saw CL, Khor TO, Pung D, Boyanapalli SS, Kong AN.(4)
5. Vulval intraepithelial neoplasia
In the evaluation of the effectiveness and safety of medical interventions for high grade Vulval intraepithelial neoplasia (VIN), a pre-malignant condition of the vulval skin, associated with infection with human papilloma virus (HPV) infection, indicated that four trials met our inclusion criteria: three assessed the effectiveness of topical imiquimod versus placebo in women with high grade VIN; one examined low versus high dose indole-3-carbinol in similar women. Meta-analysis of three trials found that the proportion of women who responded to treatment at 5 to 6 months was much higher in the group who received topical imiquimod than in the group who received placebo (relative risk (RR) = 11.95, 95% confidence interval (CI) 3.21 to 44.51), according to "Medical interventions for high grade vulval intraepithelial neoplasia" by Pepas L, Kaushik S, Bryant A, Nordin A, Dickinson HO.(5)
6. Estrogen Metabolism
In the investigation of determine whether a breast health supplement containing indole-3-carbinol and hydroxymatairesinol lignan would alter estrogen metabolism to favour C-2 hydroxylation and reduce C-16 hydroxylation, found that Supplementation with a mixture of indole-3-carbinol and HMR lignan in women significantly increased estrogen C-2 hydroxylation. This may constitute a mechanism for the reduction of breast cancer risk as well as risk for other estrogen-related cancers. Further studies with higher numbers of subjects are indicated, according to "Effects of A Breast-Health Herbal Formula Supplement on Estrogen Metabolism in Pre- and Post-Menopausal Women not Taking Hormonal Contraceptives or Supplements: A Randomized Controlled Trial" by Laidlaw M, Cockerline CA, Sepkovic DW.(6)
7. Oral cancer
In the investigation ofthe antitumor effects of OSU-A9, a structurally optimized I3C derivative, in a panel of oral squamous cell carcinoma cell lines, SCC4, SCC15, and SCC2095, showed that The antiproliferative effect of OSU-A9 was approximately two-orders-of-magnitude higher than that of I3C. Importantly, normal human oral keratinocytes were less sensitive to OSU-A9 than oral cancer cells. This antiproliferative effect of OSU-A9 was attributable to the induction of mitochondrial-dependent apoptosis as evidenced by sub-G1 accumulation of cells, poly ADP-ribose polymerase cleavage, and cytochrome c release from the mitochondria. OSU-A9 down regulates Akt and NF-κB signaling pathways, leading to changes in many downstream effectors involved in regulating cell cycle and apoptosis, according to "A novel indole-3-carbinol derivative inhibits the growth of human oral squamous cell carcinoma in vitro" by Weng JR, Bai LY, Omar HA, Sargeant AM, Yeh CT, Chen YY, Tsai MH, Chiu CF.(7)
8. Cancer prevention
In the review of botanical and nutritional compounds have been used for the treatment of cancer throughout history, indicated that several lead compounds, such as genistein (from soybeans), lycopene (from tomatoes), brassinin (from cruciferous vegetables), sulforaphane (from asparagus), indole-3-carbinol (from broccoli), and resveratrol (from grapes and peanuts) are in preclinical or clinical trials for cancer chemoprevention. Phytochemicals have great potential in cancer prevention because of their safety, low cost, and oral bioavailability, according to "Cancer prevention with natural compounds" by Gullett NP, Ruhul Amin AR, Bayraktar S, Pezzuto JM, Shin DM, Khuri FR, Aggarwal BB, Surh YJ, Kucuk O.(8)
9. Nasopharyngeal cancer
In the examination of the apoptotic effects of indole-3-carbinol (I3C) in many human cancer cells, found that Treatment with I3C significantly suppressed XIAP, c-IAP1 and Survivin protein, while elevated the expression of Omi, Smac and Cyto-c. Fas/FasL and MAPK pathway were involved in the induction of apoptosis. Taken together, these results demonstrated that I3C may induce mitochondria-mediated apoptosis via the Fas death receptor in CNE-2 cells. This molecular mechanism for apoptotic effect of I3C on nasopharyngeal cancer cells suggested that I3C might become a preventive and therapeutic agent against nasopharyngeal cancer, according to "Indole-3-carbinol (I3C)-induced apoptosis in nasopharyngeal cancer cells through Fas/FasL and MAPK pathway" by Xu Y, Zhang J, Dong WG.(9)
10. Colon cancer
In an easy two-step synthesis for 4-methoxyindole-3-carbinol (4MeOI3C), the expected breakdown product of 4-methoxyglucobrassicin during ingestion. 4MeOI3C inhibited the proliferation of human colon cancer cells DLD-1 and HCT 116 with IC(50) values of 116 microM and 96 microM, respectively, found that after 48 h in vitro, and is therefore a more potent inhibitor than indole-3-carbinol (I3C). 4MeOI3C and I3C combined in different molar ratios inhibited proliferation in a nearly additive to slightly synergistic manner. Proliferation was inhibited by 100 microM 4MeOI3C after 48 h without affecting cell cycle phase distribution, indicating an overall-slowdown effect on the cell cycle, according to "Effect of 4-methoxyindole-3-carbinol on the proliferation of colon cancer cells in vitro, when treated alone or in combination with indole-3-carbinol" by Kronbak R, Duus F, Vang O.(10)
11. Etc.
Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/20530686
(2) http://www.ncbi.nlm.nih.gov/pubmed/20603442
(3) http://www.ncbi.nlm.nih.gov/pubmed/21965724
(4) http://www.ncbi.nlm.nih.gov/pubmed/21837756
(5) http://www.ncbi.nlm.nih.gov/pubmed/21491403
(6) http://www.ncbi.nlm.nih.gov/pubmed/21234288
(7) http://www.ncbi.nlm.nih.gov/pubmed/20843730
(8) http://www.ncbi.nlm.nih.gov/pubmed/20709209
(9) http://www.ncbi.nlm.nih.gov/pubmed/20628834
(10) http://pubs.acs.org/doi/abs/10.1021/jf101806t
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