Thursday, December 1, 2011

Phytochemicals in Foods - 11 Health Benefits of Genistein

Genistein is a phytochemical in the Isoflavones, belonging to the group of Flavonoids (polyphenols), found abundantly in food of the family of legumes, soy, alfalfa sprouts, red clover, chickpeas, peanuts, etc.

Health Benefits
1. Bladder Cancer
In a phase 2 randomized, placebo-controlled trial investigated whether daily, oral genistein (300 or 600 mg/day as the purified soy extract G-2535) for 14-21 days before surgery alters molecular pathways in bladder epithelial tissue in 59 subjects diagnosed with urothelial bladder cancer (median age 71), found that G-2535 treatment was well tolerated; observed toxicities were primarily mild to moderate gastrointestinal or metabolic and usually not attributed to study drug. Genistein was detected in plasma and urine of subjects receiving G-2535 at concentrations greater than placebo subjects' but were not dose-dependent. Reduction in bladder cancer tissue p-EGFR staining between the placebo arm and the combined genistein arms was significant at the protocol-specified significance level of 0.10 (p=0.07), according to "A Phase 2 Cancer Chemoprevention Biomarker Trial of Isoflavone G-2535 (Genistein) in Presurgical Bladder Cancer Patients" by Messing E, Gee JR, Saltzstein DR, Kim K, Disant'agnese PA, Kolesar J, Harris L, Faerber A, Havighurst TC, Young JM, Efros M, Getzenberg RH, Wheeler MA, Tangrea J, Parnes HL, House M, Busby JE, Hohl RJ, Bailey HH.(1)

2. Immunomodulation And Anti-Inflammation
In the review of new concepts have emerged in relation to mechanisms that contribute to the regulation of carcinogenesis processes and associated inflammatory effects, found that the effects of polyphenols on the adaptative and innate immune cells that could infiltrate the tumor. Reduction of chronic inflammation or its downstream consequences may represent a key mechanism in the fight of cancer development and polyphenols could reduce various pro-inflammatory substance productions through targeting signal transduction or through antioxidant effects, according to "Immunomodulation And Anti-Inflammatory Roles Of Polyphenols As Anticancer Agents" by Ghiringhelli F, Rébé C, Hichami A, Delmas D.(2)

3. Bone density
In the investigation of the association between habitual phyto-oestrogen intake and broadband ultrasound attenuation (BUA) of the calcanaeum as a marker of bone density, found that the non-soya isoflavones formononetin and biochanin A were marginally significant or significantly associated with BUA in postmenopausal women (β = 1·2; P < 0·1) and men (β = 1·2; P < 0·05), respectively; enterolignans and equol were positively associated with bone density in postmenopausal women, but this association became non-significant when dietary Ca was added to the model. In the lowest quintile of Ca intake, soya isoflavones were positively associated with bone density in postmenopausal women (β = 1·4; P < 0·1), according to "Association between dietary phyto-oestrogens and bone density in men and postmenopausal women" by Kuhnle GG, Ward HA, Vogiatzoglou A, Luben RN, Mulligan A, Wareham NJ, Forouhi NG, Khaw KT.(3)

4. Antioxidant effects
In the testing effects of the soy isoflavone genistein on antioxidant enzymes in DU145 prostate cancer cells, found that Genistein significantly decreased reactive oxygen species levels and induced the expression of the antioxidant enzymes manganese (Mn) superoxide dismutase (SOD) and catalase, which were associated with AMP-activated protein kinase (AMPK) and phosphatase and tensin homolog deleted from chromosome 10 (PTEN) pathways. The induced expression of catalase, MnSOD, and PTEN were attenuated by pretreatment with a pharmacological inhibitor for AMPK. Furthermore, PTEN is essential for genistein activity, as shown by PTEN transfection in PTEN-deficient PC3 cells. Thus, genistein induces antioxidant enzymes through AMPK activation and increased PTEN expression. indicating the effects of genistein primarily depend on AMPK, according to "The antioxidant effects of genistein are associated with AMP-activated protein kinase activation and PTEN induction in prostate cancer cells" by Park CE, Yun H, Lee EB, Min BI, Bae H, Choe W, Kang I, Kim SS, Ha J.(4)

5. Anti cancers
In the determination of Genistein, the predominant isoflavones found in soy, has been shown to inhibit the carcinogenesis in animal models, indicated that there are growing body of experimental evidence that show the inhibition of human cancer cells by genistein through the modulation of genes that are related to the control of cell cycle and apoptosis. Moreover, it has been shown that genistein inhibits the activation of NF-kappa B and Akt signaling pathways, both of which are known to maintain a homeostatic balance between cell survival and apoptosis. Genistein is commonly known as phytoestrogen, which targets estrogen- and androgen-mediated signaling pathways in the processes of carcinogenesis, according to "Soy isoflavones and cancer prevention" by Sarkar FH, Li Y.(5)

6. Prostate cells
In the investigation of the hypothesis that the soy-isoflavone genistein could protect DNA of LAPC-4 prostate cells from oxidative stress-related damage by enhancing the expression of antioxidative genes and proteins, found that genistein protects prostate cells from oxidative stress-related DNA damage presumably by inducing the expression of antioxidative products, such as metallothioneins. Genistein, therefore, might counteract the age-related decline of important antioxidative defence systems which in turn maintain DNA integrity, according to "Genistein protects prostate cells against hydrogen peroxide-induced DNA damage and induces expression of genes involved in the defence against oxidative stress" by
Raschke M, Rowland IR, Magee PJ, Pool-Zobel BL(6)

7. Breast cancer
In the investigation of the potential preventive effects of lycopene and genistein, alone and in combination, on breast cancer development in female Wistar rats treated with 7,12-dimethylbenz[a]anthracene (DMBA), a carcinogen known to induce breast tumors.
found that treatment was continued for 20 wk. Rats treated with DMBA developed mammary tumors with 100% tumor incidence during the 20-wk study. Inhibition of mammary cancer incidence by lycopene (70%), genistein (60%) and their combination (40%) was observed. Tumor weight decreased by 48%, 61%, and 67%, and mean tumor volume decreased by 18%, 35%, and 65% with lycopene, genistein, and lycopene + genistein, respectively (P < 0.01 for the combination). The proportions of adenocarcinoma masses decreased with lycopene and genistein combination (P < 0.05). Administration of lycopene and genistein combination suppressed breast cancer development and was associated with a decrease in MDA, 8-isoprostane, and 8-OhdG levels and with an increase in serum lycopene and genistein levels. Animals administered DMBA developed breast cancer, which was associated with increased expression of Bcl-2 and decreased expression of Bax, caspase 3, and caspase 9 in mammary tissues, according to "Inhibitory effects of combination of lycopene and genistein on 7,12- dimethyl benz(a)anthracene-induced breast cancer in rats" by Sahin K, Tuzcu M, Sahin N, Akdemir F, Ozercan I, Bayraktar S, Kucuk O.(7)

8. Neuroprotective effects
in the investigation of whether GEN could alleviate oxidative damage induced by beta-amyloid peptides 25-35 (Abeta25-35) in PC12 cells, found that GEN attenuated the cytotoxicity and partially prevented apoptosis induced by Abeta25-35. GEN dramatically attenuated ROS levels induced by Abeta25-35 in PC12 cells. In addition, GEN significantly reversed the reduction of MMP caused by Abeta25-35 to maintain the normal levels of the cells. The GSH/GSSG ratio in GEN pretreated groups significantly increased compared to the groups without GEN pretreatment. GEN reversed Abeta25-35 induced down regulation of the protein expression of gamma-GCS, Nrf2 and HO-1, according to "Genistein as a neuroprotective antioxidant attenuates redox imbalance induced by beta-amyloid peptides 25-35 in PC12 cells" by Ma W, Yuan L, Yu H, Ding B, Xi Y, Feng J, Xiao R.(8)

9. Anti diabetes
In the investigation of the effect of genistein on beta-cell proliferation and cellular signaling related to this effect and further determined its antidiabetic potential in insulin-deficient diabetic mice, found that genistein induced protein expression of cyclin D1, a major cell-cycle regulator essential for beta-cell growth. Dietary intake of genistein significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in streptozotocin-induced diabetic mice, concomitant with improved islet beta-cell proliferation, survival, and mass. These results demonstrate that genistein may be a natural antidiabetic agent by directly modulating pancreatic beta-cell function via activation of the cAMP/PKA-dependent ERK1/2 signaling pathway, according to "Genistein induces pancreatic beta-cell proliferation through activation of multiple signaling pathways and prevents insulin-deficient diabetes in mice" by Fu Z, Zhang W, Zhen W, Lum H, Nadler J, Bassaganya-Riera J, Jia Z, Wang Y, Misra H, Liu D.(9)

10. Bone homeostasis
In the deiermination of the effect of genistein on bone homeostasis in mandibular subchondral bone of rats.Methods:Female SD rats were administered with genistein (10 and 50 mg/kg) or placebo by oral gavage for 6 weeks, found that the low and high doses of genistein significantly increased the expression of ERβ, while ERα expression was increased by the low dose genistein and decreased by the high dose genistein. ERβ silencing abrogated most of the effects of genistein treatment.Conclusion:In rat mandibular condylar subchondral bone, low-dose genistein increases bone formation and inhibit bone resorption, while excess genistein inhibits both bone formation and resorption, according to"Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone" by
Li YQ, Xing XH, Wang H, Weng XL, Yu SB, Dong GY.(10)

11. Obesity
In the study of the role of ER alpha and ER beta in a model of nutrition induced obesity, found that Treatment with E2 and Alpha decreased body weight, total cholesterol and VLDL. Visceral fat mass, adipocyte size, and serum leptin were reduced by E2, Alpha and Beta. In the soleus muscle, treatment with E2 and Beta modulated Igf1 and Pax7 gene expression and resulted in larger muscle fibers, according to "Impact of estradiol, ER subtype specific agonists and genistein on energy homeostasis in a rat model of nutrition induced obesity" by
Weigt C, Hertrampf T, Zoth N, Fritzemeier KH, Diel P.(11)



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