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  2. Pterostilbene ameliorates oxidative damage and ferroptosis in human ovarian granulosa cells by regulating the Nrf2/HO-1 pathway

Pterostilbene ameliorates oxidative damage and ferroptosis in human ovarian granulosa cells by regulating the Nrf2/HO-1 pathway

  • Arch Biochem Biophys. 2023 Mar 9;738:109561. doi: 10.1016/j.abb.2023.109561.
Xin Chen 1 Qian Lin Song 2 Ze Hong Li 1 Rui Ji 1 Jia Yu Wang 1 Ming Liang Cao 3 Xue Feng Mu 3 Yan Zhang 4 Duan Ying Guo 5 Jing Yang 6
Affiliations

Affiliations

  • 1 Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, Hubei, China.
  • 2 Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
  • 3 Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China.
  • 4 Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address: RM002125@whu.edu.cn.
  • 5 Longgang District People's Hospital of Shenzhen, Shenzhen, China. Electronic address: Guo.duanying@163.com.
  • 6 Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, Hubei, China. Electronic address: dryangjing@whu.edu.cn.
Abstract

The survival of ovarian granulosa cells is of great significance to the physiological maintenance of the ovary. Oxidative damage to the ovarian granulosa cells can lead to various diseases related to ovarian dysfunction. Pterostilbene exerts many pharmacological effects, such as anti-inflammatory and cardiovascular protective effects. Moreover, pterostilbene was shown to have antioxidant properties. This study aimed to investigate the effect and underlying mechanism of pterostilbene on oxidative damage in ovarian granulosa cells. Ovarian granulosa cell (OGC) lines COV434 and KGN were exposed to H2O2 to establish an oxidative damage model. After treatment with different concentrations of H2O2 or pterostilbene, the cell viability, mitochondrial membrane potential, oxidative stress, and iron levels were detected, and the expression of ferroptosis-related and Nrf2/HO-1 signaling pathway-related proteins were evaluated. Pterostilbene treatment could effectively improve cell viability, reduce oxidative stress, and inhibit Ferroptosis stimulated by H2O2. More importantly, pterostilbene could up-regulate Nrf2 transcription by stimulating histone acetylation, and inhibition of Nrf2 signaling could reverse the therapeutic effect of pterostilbene. In conclusion, this research shows that pterostilbene protects human OGCs from oxidative stress and Ferroptosis through the Nrf2/HO-1 pathway.

Keywords

Ferroptosis; Nrf2/HO -1 pathway; Ovarian granulosa cell; Oxidative damage; Pterostilbene.

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