6-Gingerol alleviates placental injury in preeclampsia by inhibiting oxidative stress via BNIP3/LC3 signaling-mediated trophoblast mitophagy

Frontiers in Pharmacology

Pharmacology

Weiyi Qi¹  Anna Li²  Zhenya Fang²  Shuxian Li²  Changqing Zhang²  Meijuan Zhou²  Junjun Guo²  Meihua Zhang²  Man Zhao²  Zexin Yang²  Xietong Wang³ 

[1] Department of Clinical Medicine, Shandong First Medical University, Jinan, China;Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China;Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China;Department of Obstetrics and Gynecology, Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China;

关键词: 6-gingerol;    preeclampsia;    mitophagy;    trophoblast;    oxidative stress;   

DOI  :  10.3389/fphar.2023.1243734

 received in 2023-06-22, accepted in 2023-09-25,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background and aims: Preeclampsia (PE) is the leading cause of maternal and fetal morbidity and mortality worldwide. Apoptosis of trophoblast cells induced by oxidative stress is a principal reason of placental injury in PE. 6-Gingerol, an antioxidant from ginger, plays an important role in many disease models, but its effect on obstetric diseases has not been elucidated. In this study, we investigated the protective effect of 6-gingerol against placental injury.Methods: In vitro hypoxia/reoxygenation (H/R) model of HTR8/Svneo cells and preeclamptic mice model were established to simulate PE. The effects of 6-Gingerol on PE were evaluated by morphological detection, biochemical analysis, and Western blot.Results: We found that H/R treatment induced cell apoptosis, increased the production of reactive oxygen species, malondialdehyde and lactate dehydrogenase, and decreased superoxide dismutase in trophoblast. In addition, the polarization of mitochondrial membrane potential and the cellular calcium flux were also destroyed under H/R condition, which also activated BCL2-interacting protein 3 (BNIP3) and provoked excessive mitophagy. Importantly, 6-Gingerol reversed these corrosive effects. Furthermore, the placenta damage in PE-like mouse caused by the cell apoptosis, oxidative stress and mitophagy was mitigated by 6-Gingerol.Conclusion: These findings suggest that 6-Gingerol exerts a protective effect against placental injury in PE by reducing oxidative stress and inhibiting excessive mitophagy caused by mitochondrial dysfunction.

【 授权许可】

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Copyright © 2023 Li, Zhao, Yang, Fang, Qi, Zhang, Zhou, Guo, Li, Wang and Zhang.