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 (H2O2)-induced oxidative stress has been associated with ovarian granulosa cell apoptosis and ovarian function. Recently, a study highlighted the protective role of morroniside against H2O2-induced damage. In this study, we aimed to investigate the effects of morroniside on H2O2-stimulated rat ovarian granulosa cells and its underlying molecular mechanisms. Our results showed that H2O2 treatment suppressed cell survival and increased apoptosis in rat granulosa cells, while treatment with morroniside markedly increased H2O2-induced granulosa cell survival in a dose-dependent manner (0, 10, 50 and 100 µM). Moreover, treatment with 50 µM morroniside impeded H2O2-induced cell apoptosis. An elevation in intracellular ROS, MDA, SOD, GSH-Px, and CAT level was observed in H2O2-induced granulosa cells; however, this effect was abrogated by morroniside treatment. Further studies suggested that administration of morroniside inhibited H2O2-induced granulosa cell apoptosis and caspase-3 activity. In addition, after morroniside treatment of H2O2-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 H2O2-stimulated granulosa cells. Finally, we showed that treatment with PI3K and mTOR inhibitors reversed the protective effects of morroniside on H2O2-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.

Morroniside protect human granulosa cells against H2O2-induced oxidative damage via regulating Nrf2 and MAPK signaling pathway

“…Prieto L et al con rmed that the levels of ROS in the follicular uid of infertility patients with endometriosis are increased, while the levels of T-AOC and SOD are generally decreased [29]. Morroniside could suppressed autophagy and apoptosis in rat ovarian GCs through the PI3K/AKT/mTOR pathway [22]. Our study showed that morroniside could inhibited the levels of ROS and 8-OHdG and MDA content and increased the expression of SOD and NQO1in human ovarian GCs (Figs.…”

“…It has a variety of biological activities, such as antioxidant, anti-apoptotic, anti-in ammatory [17][18][19], which can relieve nerve pain, improve cardiovascular and liver functions [20,21]. Deng et al have con rmed that morroniside inhibitd autophagy in rats ovarian GCs by regulating the PI3K/AKT/mTOR pathway [22]. However, the effect of morroniside on oxidative stress of GCs induced by H 2 O 2 is largely unclear.…”

Morroniside attenuates nucleus pulposus cell senescence to alleviate intervertebral disc degeneration via inhibiting ROS-Hippo-p53 pathway

“…MR has been documented to possess anti-oxidation, antiinflammation, and anti-apoptosis properties (Gao et al, 2020;Deng et al, 2021;Park et al, 2021). It can exert a neuroprotective role in neurodegenerative diseases by eliminating ROS to enhance the total antioxidant capacity of the rat cortex, thereby preventing nerve cells from H 2 O 2 -induced oxidation injury (Wang et al, 2009;Yao et al, 2009;Zhang et al, 2017c;Li B et al, 2019).…”

The role of oxidative stress in ovarian aging: a review

“…OS injury initiates autophagy by inhibiting the PI3K/AKT signaling pathway, promoting the dissociation between mTORC1 and ULK1, further phosphorylating autophagy-related proteins such as Atg13 [ 184 ]. It was found that H 2 O 2 intervention in granulosa cells inhibited the PI3K/AKT/mTOR pathway and increased LC3-II/LC3-I and Beclin-1 expression [ 185 ]. Activation of AKT regulates the cell cycle by regulating the function of cell cycle proteins (cyclins).…”