Astragaloside IV regulates autophagy-mediated proliferation and apoptosis in a rat model of PCOS by activating the PPARγ pathway

• Published in: Iranian journal of basic medical sciences Vol. 25; no. 7; pp. 882 - 889
• Main Authors: Wen, Mingxiao, Chen, Wenjun, Zhou, Qun, Dou, Xiaoqing
• Format: Journal Article
• Language: English
• Published: Mashhad Mashhad University of Medical Sciences 01.07.2022
• Subjects: Apoptosis; astragaloside iv; Autophagy; Original; Ovaries; Polycystic ovary syndrome; pparγ; Protein expression; rat; Rodents
• ISSN: 2008-3866; 2008-3874
• DOI: 10.22038/ijbms.2022.64475.14179

Objective(s): Astragaloside IV (AS-IV) is a bioactive saponin with a wide range of pharmacological effects. This study was aimed at investigating its potential effect on polycystic ovary syndrome (PCOS). Materials and Methods:Female Sprague-Dawley rats were randomly divided into five groups (control, PCOS, PCOS+AS-IV 20 mg/kg, PCOS+AS-IV 40 mg/kg, and PCOS+AS-IV 80 mg/kg). The pathological injury level of rat ovary was observed with hematoxylin-eosin (H&E) staining; enzyme-linked immunosorbent assay (ELISA) kit was utilized to measure the levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone in rat serum; western blot detected autophagy-associated or peroxisome proliferator-activated receptor γ (PPARγ) pathway-related protein expression; immunofluorescence was performed to observe LC3 level in rat ovarian tissue. After co-treatment with AS-IV and PPARγ inhibitor, the proliferation in ovarian granulosa cell line KGN was examined employing cell counting kit-8 (CCK-8), EdU staining, and colony formation; cell apoptosis was observed with TdT-mediated dUTP nick-end labeling (TUNEL); apoptosis-related protein expression was assayed by western blot. Results: Treatment with AS-IV inhibited the ovarian pathological damage in PCOS rats. It also promoted the level of autophagy and activated PPARγ signaling in the rat PCOS model. In KGN cells, the level of autophagy and expression of PPARγ-related proteins were also elevated by AS-IV treatment. Furthermore, AS-IV facilitated autophagy, thus inhibiting KGN cell proliferation and promoting its apoptosis, through activating the PPARγ signaling pathway. Conclusion: AS-IV-activated PPARγ inhibits proliferation and promotes the apoptosis of ovarian granulosa cells, enhancing ovarian function in rats with PCOS.