Morroniside suppresses hydrogen peroxide-stimulated autophagy and apoptosis in rat ovarian granulosa cells.

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n/a PMID: Hum Exp Toxicol. 2021 Apr ;40(4):577-586. Epub 2020 Sep 21. PMID: 32954801 Abstract Title: Morroniside suppresses hydrogen peroxide-stimulated autophagy and apoptosis in rat ovarian granulosa cells through the PI3K/AKT/mTOR pathway. Abstract: Previous evidences have indicated that granulosa cells play a critical role in follicular growth. Hydrogen peroxide (HO)-induced oxidative stress has been associated with ovarian granulosa cell apoptosis and ovarian function. Recently, a study highlighted the protective role of morroniside against HO-induced damage. In this study, we aimed to investigate the effects of morroniside on HO-stimulated rat ovarian granulosa cells and its underlying molecular mechanisms. Our results showed that HOtreatment suppressed cell survival and increased apoptosis in rat granulosa cells, while treatment with morroniside markedly increased HO-induced granulosa cell survival in a dose-dependent manner (0, 10, 50 and 100µM). Moreover, treatment with 50 µM morroniside impeded HO-induced cell apoptosis. An elevation in intracellular ROS, MDA, SOD, GSH-Px, and CAT level was observed in HO-induced granulosa cells; however, this effect was abrogated by morroniside treatment. Further studies suggested that administration of morroniside inhibited HO-induced granulosa cell apoptosis and caspase-3 activity. In addition, after morroniside treatment of HO-stimulated granulosa cells, autophagy-related protein (LC3-II/LC3-I ratio) and beclin-1 expression was decreased and p62 level was increased. Interestingly, we found that morroniside treatment activated the PI3K/AKT/mTOR pathway in HO-stimulated granulosa cells. Finally, we showed that treatment with PI3K and mTOR inhibitors reversed the protective effects of morroniside on HO-induced granulosa cells. Taken together, our data suggest that treatment with morroniside decreased apoptosis, autophagy, and oxidative stress in rat granulosa cells through the PI3K/AKT/mTOR pathway.