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Salidroside alleviates oxidative stress and apoptosis via AMPK/Nrf2 pathway in DHT-induced human granulosa cell line
Rui Ji1, Fang-Yuan Jia2, Xin Chen1
1Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, China; Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China.
Abstract:
In the past few years, emerging evidence established persistent oxidative stress to be a key player in the pathogenesis of polycystic ovary syndrome (PCOS). Particularly, it damages the function of granulosa cells, and thus hinders the development of follicles. The present study aimed to explore and establish the protective effects of salidroside on dihydrotestosterone (DHT)-induced Granulosa-like tumor cell line (KGN), mediated via antioxidant mechanisms. The study assessed the positive effects of salidroside on DHT-induced apoptosis, reactive oxygen species (ROS) accumulation, damage of antioxidant capacity, and mitochondrial membrane potential depolarization. Interestingly, salidroside partly reversed DHT mediated effects, via stimulation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and the downstream antioxidant proteins heme oxygenase-1(HO-1) and quinine oxidoreductase 1(NQO1). Additionally, the knockdown of Nrf2 partly moderated the antioxidant and anti-apoptosis effects of salidroside in DHT-treated KGN cells. Mechanistically, AMP-activated protein kinase (AMPK) was identified to be the upstream signaling involved in salidroside-induced Nrf2 activation, as silencing of AMPK partly prevented the upregulation of Nrf2 and the downstream proteins HO-1 and NQO1. Altogether, the present study is the first to effectively demonstrate the inhibitory effect of salidroside on DHT-stimulated oxidative stress and apoptosis in KGN cells, which was dependent on Nrf2 activation that involved AMPK.
Insights
Salidroside protects against dihydrotestosterone-induced oxidative stress and apoptosis in PCOS granulosa cells. This effect is mediated by activating the Nrf2 pathway, involving upstream AMPK signaling.
Area of Science:
- Endocrinology
- Cell Biology
- Biochemistry
Background:
- Polycystic Ovary Syndrome (PCOS) pathogenesis involves persistent oxidative stress, damaging granulosa cell function and hindering follicle development.
- Dihydrotestosterone (DHT) is implicated in PCOS, potentially exacerbating oxidative stress and cellular damage in granulosa cells.
Purpose of the Study:
- To investigate the protective effects of salidroside against DHT-induced oxidative stress and apoptosis in KGN cells.
- To elucidate the underlying antioxidant mechanisms, focusing on the Nrf2 signaling pathway and its upstream regulators.
Main Methods:
- KGN cells were treated with DHT to induce oxidative stress and apoptosis.
- Salidroside treatment was assessed for its effects on reactive oxygen species (ROS) accumulation, antioxidant capacity, and mitochondrial membrane potential.
- Nrf2 and AMPK signaling pathways were investigated using knockdown and Western blot analyses.
Main Results:
- Salidroside partially reversed DHT-induced apoptosis, ROS accumulation, and mitochondrial damage.
- Salidroside stimulated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and its downstream targets, heme oxygenase-1 (HO-1) and quinine oxidoreductase 1 (NQO1).
- AMP-activated protein kinase (AMPK) was identified as an upstream activator of salidroside-induced Nrf2 signaling.
Conclusions:
- Salidroside exhibits significant protective effects against DHT-induced oxidative stress and apoptosis in KGN cells.
- The protective mechanism involves the activation of the AMPK/Nrf2 signaling pathway, leading to enhanced antioxidant defense.
- This study provides novel insights into the therapeutic potential of salidroside for PCOS management by targeting oxidative stress.
