Phytoestrogen-rich fraction of Millettia aboensis (Hook. f.) Baker counters high-fat-diet-induced insulin resistance and endothelial dysfunction biomarkers of menopause in ovariectomised rats

Menopause is marked by decline in oestrogen levels, leading to increased fat accumulation, insulin resistance, and endothelial dysfunction—key contributors to heightened cardiometabolic risk. Oestrogen deficiency impairs insulin signalling and vascular function through oxidative stress and lipid abnormalities. Although hormone replacement therapy (HRT) mitigates these effects, its long-term risks have spurred interest in safer alternatives like phytoestrogens. This study evaluated the effect of phytoestrogen-rich fraction (PERF) of Millettia aboensis on insulin resistance and endothelial dysfunction markers in ovariectomized (OVX) rats fed a high-fat diet (HFD). The methanol extract of M. aboensis (MA) roots was fractionated and screened for phytoestrogen content using genistein equivalence. OVX rats were fed HFD or normal diet (ND) for 10 weeks, with PERF (200 and 400 mg/kg) administeredfrom week 5. Serum levels of HOMA-IR, LDL, oxidized LDL (OxLDL), and malondialdehyde (MDA) were measured. The ethyl acetate fraction showed the highest phytoestrogen content of 115 mg GenesteinEq/g. PERF significantly (P<0.05) reduced HOMA-IR, LDL, OxLDL, and MDA in a dose-dependent manner, comparable to oestradiol, with some parameters restored to near-baseline. These findings suggest that MA may counter insulin resistance and oxidative vascular damage associated with menopause and high-fat diets, offering a potential alternative to HRT.