1. The mechanism of curcumin to protect mouse ovaries from oxidative damage by regulating AMPK/mTOR mediated autophagy.
- Author
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Duan H, Yang S, Yang S, Zeng J, Yan Z, Zhang L, Ma X, Dong W, Zhang Y, Zhao X, Hu J, and Xiao L
- Subjects
- Animals, Female, Mice, AMP-Activated Protein Kinases drug effects, AMP-Activated Protein Kinases metabolism, Apoptosis drug effects, Granulosa Cells drug effects, Hydrogen Peroxide toxicity, Nitro Compounds, Propionates pharmacology, Signal Transduction drug effects, Autophagy drug effects, Curcumin pharmacology, Ovary drug effects, Oxidative Stress drug effects, TOR Serine-Threonine Kinases drug effects, TOR Serine-Threonine Kinases metabolism
- Abstract
Background: Oxidative stress is considered the main cause of granulosa cell apoptosis in ovarian disease. Curcumin has various biological roles, but its potential role in protecting granulosa cells from oxidative damage remains unidentified., Purpose: The study revealed the protective effect of curcumin on granulosa cell survival under oxidative stress, and explored its mode of action., Study Design: The protective effect of curcumin on oxidative stress-induced ovarian cell apoptosis was evaluated in vivo and in vitro, and the role of autophagy and AMPK/mTOR signaling pathway in this process was also demonstrated., Methods: First, mice were injected to 3-nitropropionic acid (3-NPA, 20 mg/kg/day) for 14 consecutive days to establish the ovarian oxidative stress model, at same time, curcumin (50, 100, 200 mg/kg/day) was given orally. Thereafter, functional changes, cell apoptosis, and autophagy in ovarian tissue were evaluated by hematoxylin-eosin staining, enzyme-linked immunosorbent assay, western blotting, TUNEL assays, and transmission electron microscopy. Finally, oxidative stress model of granulosa cells was established with H
2 O2 in vitro and treated with curcumin. The underlying mechanisms of curcumin to protect the apoptosis under oxidative stress in vitro were determined using western blotting and TUNEL assays., Results: In our study, after curcumin treatment, the mouse ovarian function disorder under 3-nitropropionic acid-induced oxidative stress recovered significantly, and ovarian cell apoptosis decreased. H2 O2 induced granulosa cell apoptosis in vitro, and curcumin antagonized this process. Autophagy contributes to tissue and cell survival under stress. We therefore examined the role of autophagy in this process. According to the in vivo and in vitro results, curcumin restored autophagy under oxidative stress. The autophagy inhibitor (chloroquine) exhibited the same effect as curcumin, whereas the autophagy activator (rapamycin) antagonized the effect of curcumin. In addition, the study found that the AMPK/mTOR pathway plays a crucial role in curcumin- mediated autophagy to protect against oxidative stress-induced apoptosis., Conclusion: Our findings for the first time systematically revealed a new mechanism through which curcumin protects ovarian granulosa cells from oxidative stress-induced damage through AMPK/mTOR-mediated autophagy and suggested that it can be a new therapeutic direction for female ovarian diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript., (Copyright © 2024 Elsevier GmbH. All rights reserved.)- Published
- 2024
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