Short reports

Plasma concentrations of phyto-oestrogens in Japanese men

Genistein, a naturally occurring phytoestrogen and a member of the large class of compounds known as isoflavones, exerts protective effects in several diseases. Recent studies indicate that genistein plays a critical role in controlling body weight, obesity-associated insulin resistance, and metabolic disorders, but its target organs in reversing obesity and related pathological conditions remain unclear. In this study, we showed that mice supplemented with 0.2% genistein in a high-fat diet for 12 weeks showed enhanced metabolic homeostasis, including reduced obesity, improved glucose uptake and insulin sensitivity, and alleviated hepatic steatosis. We also observed a beiging phenomenon in the white adipose tissue and reversal of brown adipose tissue whitening in these mice. These changes led to enhanced resistance to cold stress. Altogether, our data suggest that the improved metabolic profile in mice treated with genistein is likely a result of enhanced adipose tissue function.

This chapter discusses the important bioactive compounds of ingredients that are commonly found in Eastern diet that may affect the risk of benign prostatic hyperplasia (BPH). These compounds include β-carotene, vitamin C, and vitamin E found in vegetables; eicosapentaenoic acid and docosahexaenoic acid found in fish; lycopene found in tomatoes; and isoflavones found in soy. Proposed mechanisms of action of these compounds on reducing the risk of BPH include antioxidative and proapoptotic effects on hyperplastic prostate tissue and modulation of growth and steroidogenic enzymes. The chapter also discusses how it compares to its Western counterpart in reducing prostate tissue proliferation.

Assessment of the potential therapeutic benefits offered by naturally occurring phytoestrogens necessitate inspection of their potency and sites of action in impeding the chronic, systemic, autoimmune, joint destructing disorder Rheumatoid arthritis (RA). Possessing structural and functional similarity with human estrogen, phytoestrogen promisingly replaces the use of hormone therapy in eradicating RA symptoms with their anti-inflammatory, anti-oxidative, anti-proliferative, anti-angiogenesis, immunomodulatory, joint protection properties abolishing the harmful side effects of synthetic drugs. Scientific evidences revealed that use of phytoestrogens from different chemical categories including flavonoids, alkaloids, stilbenoids derived from different plant species manifest beneficial effects on RA through various cellular mechanisms including suppression of pro‐inflammatory cytokines in particular tumor necrosis factor (TNF-α), interleukin(IL-6) and nuclear factor kappa B (NF-κB) and destructive metalloproteinases, inhibition of oxidative stress, suppressing inflammatory signalling pathways, attenuating osteoclastogenesis ameliorating cartilage degradation and bone erosion. This review summarizes the evidences of different phytoestrogen treatment and their pharmacological mechanisms in both in vitro and in vivo studies along with discussing clinical evaluations in RA patients showing phytoestrogen as a promising agent for RA therapy. Further investigations and more clinical trials are mandatory to clarify the utility of these plant derived compounds in RA prevention and in managing oestrogen deficient diseases in patients.

Breast cancer is one of the leading causes of cancer-related morbidity and mortality among women worldwide. Phytoestrogens, plant-derived polyphenols that structurally and functionally mimic 17β-estradiol, the mammalian estrogen hormone, are known to modulate multiple molecular targets in breast cancer cells. The structural and chemical similarities to estradiol enable phytoestrogens to exert estrogenic or antiestrogenic activities by binding to the estrogen receptors. Although phytoestrogens have low affinity for estrogen receptors, they are able to compete with 17β-estradiol for the ligand-binding domain of the receptors. Phytoestrogens trigger epigenomic effects that could be beneficial in breast cancer prevention and/or treatment. Few studies have focused on the cytotoxic and structure-activity relationships of phytoestrogen analogs and derivatives with more effective anticancer properties than their corresponding parent compounds. Phytoestrogens and their analogs and derivatives bind to estrogen receptors, with a preferential affinity for ERβ, and inhibit the growth promoting activity of ERα. These bioactive compounds also exert growth inhibitory effects through various cell signaling pathways. At the level of cell cycle, they inhibit the expression of oncogenic cyclin D1, increase the expression of cyclin-dependent kinase inhibitors (p21, p27, and p57) and tumor suppressor genes (APC, ATM, PTEN, SERPINB5). Phytoestrogens and their analogs and derivatives mediate their effects on breast cancer by inhibiting estrogen synthesis and metabolism, as well as exerting antiangiogenic, antimetastatic, and epigenetic effects. Furthermore, these bioactive compounds reverse multi-drug resistance. This review offers a comprehensive summary of current literature and future perspectives on the in vitro molecular mechanisms of the anticancer activities of phytoestrogens and their analogs and derivatives on breast cancer.

The beneficial effect of genistein has indicated on metabolic disorders and inflammatory state. The aim of this study was to investigate the effect of genistein supplementation on non-alcoholic fatty liver disease (NAFLD) as the hepatic manifest of metabolic syndrome.

In the present randomized double-blind controlled trial, patients with NAFLD were daily supplemented with either 250 mg genistein (n = 41) or placebo (n = 41) for 8-weeks. Both groups were instructed to follow an energy-balanced diet and physical activity recommendations. And their anthropometric and biochemical indices were assessed before and after the intervention.

At the end of the study, the genistein group had lower level of serum insulin (p = 0.001) and homeostasis model assessment for insulin resistance (HOMA-IR) (p = 0.041) compare to the placebo group. In addition serum malondialdehyde (MDA) (p = 0.004), tumor necrosis factor-α (TNF-α) (p = 0.045) and interleukin (IL)-6 (p = 0.018) also were lower in the genistein group. Compare with placebo, genistein supplementation significantly reduced waist to hip ratio (p = 0.021), body fat percentage (p = 0.015) and triglyceride (p = 0.018). However, there were no significant changes in BMI, fasting blood glucose (p = 0.122), alanine aminotransferase (ALT) (p = 0.536), aspartate aminotransferase (AST) (p = 0.265) between the two groups.

Oral supplementation with 250 mg genistein for 8-weeks can reduce insulin resistance, oxidative and inflammatory indices along with improvement in fat metabolism in patients with NAFLD. Studies with longer duration and larger samples might be needed to reveal other beneficial effects of genistein.

Isoflavones found in soybeans are nonsteroidal phytoestrogenic and antioxidative diphenolic compounds with potential roles in the prevention of chronic diseases, including hormone dependent cancer cardiovascular diseases, osteoporosis, and postmenopausal syndrome. Japanese consume 40–100 mg/day from various kind of soy foods, and it may contribute to the low incidence of above diseases. S(–)-equol, a metabolite of daidzein by the intestinal microflora, shows the strongest estrogenic activity among isoflavones. Epidemiology, metabolism and measurements, animal and in vitro experiments, randomized clinical study and metaanalysis, supplements, and safety are reviewed.