Erxian decoction alleviates cisplatin-induced premature ovarian failure in rats by reducing oxidation levels in ovarian granulosa cells

• Published in: Journal of ethnopharmacology 2023-03, Vol.304, p.116046-116046, Article 116046
• Main Authors: Liu, Jiao, Yang, Yang, He, Yueshuang, Feng, Chenran, Ou, Haosong, Yang, Jiadi, Chen, Yao, You, Fengming, Shao, Binghao, Bao, Jirong, Guan, Xingyu, Chen, Fangfang, Zhao, Piwen
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Animals; bcl-2-Associated X Protein - metabolism; Caspase 3 - metabolism; Cisplatin - adverse effects; Drugs, Chinese Herbal - therapeutic use; Female; Follicle Stimulating Hormone - metabolism; Granulosa Cells - metabolism; Humans; Hydrogen Peroxide - metabolism; Primary Ovarian Insufficiency - chemically induced; Primary Ovarian Insufficiency - drug therapy; Primary Ovarian Insufficiency - pathology; Rats; Reactive Oxygen Species - metabolism; Superoxide Dismutase - metabolism
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2022.116046

Erxian Decoction (EXD) has been used empirically for more than 70 years to treat premature ovarian failure (POF), but more research is needed to understand how it works. The study aims to ascertain both in vivo and in vitro rewards of EXD. EXD is composed of Curculiginis Rhizoma, Epimedii Folium, Morindae Officinalis, Angelicae Sinensis, Anemarrhenae Rhizoma, and Phellodendri Chinensis Cortex. UPLC/MS analysis was used to investigate the components of EXD. Using a POF model created by administering cisplatin to rats intraperitoneally, the pharmacodynamic effects of EXD were investigated. Three dose groups of EXD were garaged into rats: high (15.6 g/kg), medium (7.8 g/kg), and low (3.9 g/kg). By using a vaginal smear, the impact of EXD on the rat estrous cycle was evaluated. An ELISA test was used to measure the anti-Mullerian hormone (AMH), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels in the serum of rats. By using HE stains, pathological alterations in the ovaries may be seen. MDA and SOD levels in ovarian samples were used to measure the degree of ovarian oxidation. TUNEL labeling of ovarian sections was used to find apoptosis levels. By using ATP, energy production was evaluated. The relative expression of proteins connected to aging and the RAGE pathway was assessed using Western blot. Then, using H2O2, a model of senescent human ovarian granulosa cells (KGN) was created in vitro. The impact of EXD and H2O2 on cellular senescence was discovered using-galactosidase staining. Cell apoptosis levels were found using PI/Hoechest33342. By using DCFH-DA, intracellular ROS was examined. MDA and SOD concentrations were used to measure the degree of cellular oxidation. RAGE-related mRNA and protein expression were evaluated using RT-qPCR and western blotting. Using UPLC/MS analysis, 39 chemicals in EXD were found. Rats' estrous cycles were enhanced by EXD, which increased ovarian index and follicle count and reduced the proportion of atretic follicles in the rats. EXD reduced LH and FSH output while restoring AMH and E2 secretion. In ovarian tissues, EXD reduced the amount of apoptosis and MDA while raising SOD activity and ATP levels. The protein levels of p16, p21, p53, and Lamin A/C were among the senescence-related proteins that EXD lowered, along with the levels of RAGE, PI3K, BAX, and CASPASE 3. Anti-apoptotic protein BCL-2 was also raised in the RAGE pathway. Senescence, apoptosis, ROS, and MDA levels in the KGN