Safety profile and estrogenic activity of extracts and phytoestrogen rich fractions of Vitex doniana and Millettia aboensis

Hormonal therapy has been used to treat menopause associated disease conditions. However, the risks have led to increased interest in the search for effective and safe alternatives to ensure improved quality of life for menopausal women. This study investigated the safety and estrogenic potential of methanol fruit and root extracts and phytoestrogen rich fractions of V. doniana (VD) and M. aboensis (MA), respectively, in ovariectomized rats. The LD₅₀ of VD and MA extracts were 4472 and >5000 mg/kg and their ED₅₀ 128.05 and 321.58 mg/kg, respectively. Their ethyl acetate fractions (EAF) showed the highest phytoestrogen contents of 90 and 115 mg genistein Eq/g respectively. Serum inflammatory marker - NF-kb was significantly (P<0.05) reduced by 200 mg/kg EAF of MA (2.82 ± 0.27 ng/ml) compared to vehicle treated control group (5.21 ±1.13 ng/ml) while bone resorption marker, ALP, was also significantly (P<0.05) reduced by both MA (60.79 ±0.78 IU/L) and VD (72.59 ± 1.32 IU/L) compared to vehicle control (94.63 ± 0.91 IU/L). The fractions significantly (P<0.05) increased serum catalase and superoxide dismutase enzyme activities. Ovariectomization-induced elevations in serum liver and kidney enzymes were dose dependently reduced by the extract and fractions. HPLC-DAD-MS analysis of the active fractions reveled the presence of these phytoestrogens: Daidzein, tectorigenin, 5-OMe tectorigenin, 7-OMe tectotigenin, genistein, 5-O-methyl genistein in VD and derrisoflavone derivatives in MA. MA and VD showed good estrogenic activities and a wide margin of effective and toxic doses that support their use for chronic management of menopause associated disease conditions.