Therapeutic effects of <i>Malus floribunda</i> extract on letrozole-induced insulin resistance in rats

Abstract Objectives The present study aimed to investigate the therapeutic effects of Malus floribunda fruit ethanol extract on metabolic parameters and insulin signalling in a letrozole-induced PCOS-associated insulin resistance model. Methods 60 female Sprague-Dawley rats were randomly allocated into five groups: Healthy Control, IR, IR + Metformin (300 mg/kg), IR + MF250, and IR + MF500. Treatments were administered orally for 15 days. Fasting insulin, HOMA-IR, OGTT, lipid profile, and reproductive hormones were assessed. Histological and IHC analyses of InR, IRS-1, and IRS-2 were performed on muscle and adipose tissues. Results The IR group exhibited significantly elevated insulin (p&lt;0.001), HOMA-IR (p&lt;0.001), testosterone, triglycerides, LDL, and total cholesterol levels, with reduced HDL and oestrogen levels compared to controls. Treatment with M. floribunda , particularly at 500 mg/kg, significantly improved insulin levels (p&lt;0.001), HOMA-IR (p&lt;0.001), lipid profile, and hormonal parameters. IHC analysis revealed suppressed InR, IRS-1, and IRS-2 expression in muscle and adipose tissues of the IR group, which was restored following M. floribunda treatment. Conclusions M. floribunda extract administration, particularly at 500 mg/kg, significantly improved glucose homeostasis, lipid metabolism, hormonal balance, and insulin signalling pathway components (InR, IRS-1, IRS-2) in a letrozole-induced PCOS-associated insulin resistance model. These findings suggest that M. floribunda may serve as a promising alternative therapeutic agent for insulin resistance management.