Wajid Mohammad Sheikh, Jasmeena Jan, Atif Khurshid Wani, Majid Shafi, Ishraq Hussain, Indrani Jadhav, Showkeen Muzamil Bashir
Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder characterized by reproductive dysfunction, oxidative stress, and metabolic abnormalities. The present study investigated the therapeutic efficacy of a hydroalcoholic extract of Anchusa strigosa in a letrozole-induced PCOS rat model and explored its effects on ovarian Wnt signaling. Female Wistar rats (n = 36) were divided into normal control, PCOS control, A. strigosa low-dose (100 mg/kg), A. strigosa high-dose (250 mg/kg), and metformin (50 mg/kg) groups. Phytochemical profiling by FTIR and GC-MS identified 114 bioactive compounds enriched with phenolic, thiol, and isothiocyanate functional groups. Letrozole administration significantly increased body weight from 174.33 ± 1.80 g to 249.66 ± 1.66 g and elevated malondialdehyde levels from 45.42 ± 1.92 to 70.20 ± 1.51 while reducing superoxide dismutase from 28.97 ± 0.55 to 16.82 ± 0.59 and glutathione from 4.09 ± 0.07 to 1.83 ± 0.10 compared with normal controls. Treatment with A. strigosa, particularly at 250 mg/kg, markedly restored estrous cyclicity, reduced final body weight to 225.27 ± 0.57 g, decreased malondialdehyde to 60.90 ± 0.48, improved superoxide dismutase to 22.57 ± 0.27 and glutathione to 3.22 ± 0.09, normalized reproductive hormones and lipid profiles, restored ovarian morphology, and significantly upregulated ovarian Wnt7a and Wnt8b gene and protein expression. Although metformin produced slightly superior therapeutic effects, A. strigosa demonstrated comparable efficacy across most reproductive and metabolic parameters, highlighting its multi-target pharmacological potential. These findings suggest that A. strigosa represents a promising phytotherapeutic candidate for PCOS management. Future studies should focus on isolation of its active constituents, elucidation of the molecular mechanisms underlying Wnt pathway modulation, long-term safety evaluation, and well-designed clinical trials to establish its translational applicability in human PCOS.