genistin and Atrophy

Genistein, the principal isoflavone present in soy, has been identified as a protein tyrosine kinase (PTK) inhibitor that has in vitro anti-inflammatory effects. Whether genistein has in vivo anti-inflammatory effects remains unknown yet. Injecting or feeding rats with the unconjugated form of genistein (aglycone) results in decreased thymic weight and lymphocytopenia. However, 95-99% of genistein is present as the conjugated form genistin (genistein glycoside) in soy or soy-derived products. This study was undertaken to reveal whether genistin, as well as genistein, has anti-inflammatory effects in vivo. After oral administration of equimolar genistein (namely 7.4 or 74 micromol/dose) at daily doses of 2.0 or 20 mg/kg, or genistin at daily doses of 3.2 or 32 mg/kg for 3 days to male rats, both aglycone and glycoside suppressed the production of lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6 in both from the liver and in the sera. Aglycone induced thymic atrophy while glycoside did not. In vitro preincubation of liver slices from naïve rat with genistein aglycone or glycoside suppressed LPS-induced TNF-alpha production in a dose-dependent manner. Taken together, both in vivo and in vitro administration of genistin and genistein suppressed LPS-induced liver pro-inflammatory cytokine production. However, equimolar oral administration of genistin did not induce thymus atrophy. Further investigation in long-term isoflavone intake is required especially among neonates. The results suggest that the safety evaluation of the consumption of isoflavone should be based on isoflavone glycoside but not aglycone.

Topics: Administration, Oral; Animals; Atrophy; Chemical and Drug Induced Liver Injury; Chromatography, High Pressure Liquid; Diet; Disease Models, Animal; Dose-Response Relationship, Drug; Genistein; Glycine max; In Vitro Techniques; Interleukins; Isoflavones; Lipopolysaccharides; Liver; Male; Microdissection; Rats; Rats, Wistar; Thymus Gland; Tumor Necrosis Factor-alpha

The effects of the soy isoflavone glycoside, daidzin, genistin, and glycitin on bone loss and lipid metabolism in ovariectomized (ovx) rats were compared with those of estrone. Thirty-six 11-week-old female Sprague-Dawley rats were assigned to six groups, sham-operated, ovx, ovx+glycitin, ovx+daidzin, ovx+genistin, and ovx+estrone and fed matched amounts of a commercial calcium-deficient diet for 4 weeks. Throughout this period, daidzin, genistin or glycitin (25, 50 or 100 mg/kg/d) was given orally using a stomach tube, or estrone (7.5 microg/kg/d) was administered subcutaneously. Daidzin, genistin and glycitin significantly prevented bone loss in ovx rats at a dose of 50 mg/kg/d, like estrone. At this dose glycitin and daidzin also prevented ovx-induced uterine atrophy and increases in body weight gain, abdominal fat, serum total cholesterol and triglyceride, and urinary excretion of pyridinoline and deoxypyridinoline with statistical significance, like estrone. On the other hand, genistin prevented ovx-induced uterine atrophy only at a dose of 100 mg/kg, but did not block any other change of ovx rats at a dose of 50 or 100 mg/kg. These findings indicate that daidzin, glycitin, and genistin are effective in preventing bone loss and the former two compounds are effective in reversing the unfavorable changes of lipid metabolism in this model. It is suggested that the preventive effect of daidzin or glycitin on bone loss in ovx rats is due to suppression of bone turnover, as in the case of estrone, but genistin has a different mechanism of action from the other compounds. Soy isoflavone glycosides may represent a potential alternative therapy in the treatment of bone loss and lipid metabolism abnormality in ovarian hormone-deficient women.

Topics: Adipose Tissue; Animals; Atrophy; Calcium; Eating; Female; Glycine max; Isoflavones; Lipid Metabolism; Ovariectomy; Phosphorus; Rats; Rats, Sprague-Dawley; Uterus; Weight Gain