Aqueous Ethanolic Extract of Inonotus obliquus Ameliorates Polycystic Ovarian Syndrome by Modulating Oxidative Stress and Downregulating TNF-α and Interleukin-6

Polycystic ovarian syndrome (PCOS) is a complex metabolic and endocrine disorder with multifactorial etiology and complex pathogenesis. These intrinsic physiological changes cause anovulation, infertility, and miscarriage in women and exacerbate their chances of becoming hyperlipidemic and diabetic. Inonotus obliquus has been used traditionally for infertility problems. The present study aimed to investigate the therapeutic effects of aqueous ethanolic extract of Inonotus obliquus (AEIO) in female rats with letrozole-induced PCOS, along with the determination of its possible mechanism. HPLC analysis revealed the presence of gallic acid, chlorogenic acid, rutin, p-coumaric, benzoic acid, quercetin, salicylic acid, and kaempferol. Thirty female albino rats were acquired and divided into two groups (5 + 25) to induce PCOS. Letrozole (1 mg/kg) was used to induce the disease for 7 weeks (25 rats) except for the normal control (5 rats). The disease was confirmed by vaginal smear cytology, weight gain, and endocrinopathy. After disease induction, rats were divided into five groups (five rats in each group; disease control, metformin 20 mg/kg, AEIO 100, 300, and 500 mg/kg). After completion of the study, the animals were euthanized under the influence of anesthesia (chloroform). Ovaries were removed for histopathology, the liver was evaluated for oxidative stress biomarkers, and blood samples were collected for biochemical evaluation. Ovarian histopathology showed an abnormal architecture with cystic follicles and abnormal granulosa cells. Interestingly, treatment with AEIO restored normal ovarian histology with primary, growing, and developing follicles. After conducting a hormonal analysis, it was found that the induction of PCOS led to a significant increase (p  <  0.001) in luteinizing hormone (LH), insulin, and testosterone levels, while the levels of follicle-stimulating hormone (FSH) decreased. However, treatment with AEIO at doses of 100–500 mg/kg restored these levels to normal. PCOS induction also resulted in oxidative stress and lipid peroxidation by significantly decreasing antioxidant enzymatic markers (SOD, CAT, and GSH) and increasing levels of lipid peroxidation enzymatic markers (MDA). AEIO restored the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), and reduced the level of malondialdehyde (MDA). In conclusion, antioxidant phytochemicals (gallic acid, chlorogenic acid, rutin, p-coumaric, benzoic acid, quercetin, salicylic acid, and kaempferol) rich extract alleviated PCOS symptomatology through modulating oxidative stress markers and eliminating ovarian low-grade inflammation by downregulating the expression of NF-κB associated TNF-α and IL-6.