Preventive and therapeutic effects of genistein and daidzein on anxiety-like behaviors in ovariectomized rats.

Estrogen has demonstrated beneficial effects; however, it can also have unfavorable effects. Phytoestrogens are present in many consumable products and commonly used as supplements. These are of interest as they may have beneficial effects on mood with fewer undesirable effects on reproductive tissues. This study investigated the anxiolytic-like effects of the phytoestrogens genistein and daidzein on ovariectomized (Ovx) rats and their effects on the expression of uterine estrogen receptors (ER) and brain monoamines. In experiment 1, Ovx rats received either vehicle, 17β-estradiol, or 0.25 - 1 mg/kg of genistein or daidzein for 4 weeks before behavioral tests of anxiety. In experiment 2, we assessed the therapeutic effects of genistein and daidzein. The ovariectomies were used to induce anxiety, so the treatments were started 3 weeks post-ovariectomy. The Ovx rats received vehicle, 17β-estradiol, or 0.25 mg/kg of genistein or daidzein daily for 4 weeks before behavioral tests. We found daidzein and genistein comparable to 17β-estradiol in their anxiolytic-like effects. Further, while 17β-estradiol decreased body weight gain, increased uterine weight, and increased the uterine ERα/ERβ ratio, neither genistein nor daidzein had these undesirable effects. The alterations in brain monoamines following genistein or daidzein treatments were somewhat different from those seen after 17β-estradiol treatment. In conclusion, daily daidzein or genistein administration for 4 weeks did not negatively affect body weight, food intake, uterine tissue, uterine ER expressions, or ERα/ERβ ratio but demonstrated anxiolytic-like effects on Ovx rats. We conclude that low-dose (0.25 mg/kg) genistein or daidzein can alleviate anxiety in a female anxious rat model.