Abstract
Gastrodin (GAS) is the main bioactive component of Tianma, a traditional Chinese medicine widely used to treat neurological disorders as well as cardio- and cerebrovascular diseases. In the present study, the protective effects of GAS on H9c2 cells against ischemia–reperfusion (IR)-like injury were found to be related to decreasing of oxidative stress. Furthermore, GAS could protect H9c2 cells against oxidative injury induced by H2O2. Pretreatment of GAS at 20, 50, and 100 μM for 4 h significantly ameliorated the decrease in cell viability and increase in apoptosis of H9c2 cells treated with 400 μM H2O2 for 3 h. Furthermore, we showed that H2O2 treatment induced fragmentation of mitochondria and significant reduction in networks, footprint, and tubular length of mitochondria; H2O2 treatment strongly inhibited mitochondrial respiration; H2O2 treatment induced a decrease in the expression of mitochondrial fusion factors Mfn2 and Opa1, and increase in the expression of mitochondrial fission factor Fis1. All these alterations in H2O2-treated H9c2 cells could be ameliorated by GAS pretreatment. Moreover, we revealed that GAS pretreatment enhanced the nuclear translocation of Nrf2 under H2O2 treatment. Knockdown of Nrf2 expression abolished the protective effects of GAS on H2O2-treated H9c2 cells. Our results suggest that GAS may protect H9c2 cardiomycytes against oxidative injury via increasing the nuclear translocation of Nrf2, regulating mitochondrial dynamics, and maintaining the structure and functions of mitochondria.
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Acknowledgements
This work was supported by the Chen-Kai-Xian Academician Workstation in Yunnan Province (No. 2017IC041), National Natural Science Foundation of China (Nos. 81873056 and 81872496), and the Open Project of the State Key Laboratory of Innovative Natural Medicine and Traditional Chinese Medicine Injections (No. QFSKL2018006).
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QQC conducted the experiments, analyzed the data, and drafted the paper. YWW participated in the experiments. WMY, MHT, YCW, and HYH helped to design the experiments. WDZ and XL supervised the research and revised the paper. All authors reviewed and approved the paper.
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Cheng, Qq., Wan, Yw., Yang, Wm. et al. Gastrodin protects H9c2 cardiomyocytes against oxidative injury by ameliorating imbalanced mitochondrial dynamics and mitochondrial dysfunction. Acta Pharmacol Sin 41, 1314–1327 (2020). https://doi.org/10.1038/s41401-020-0382-x
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DOI: https://doi.org/10.1038/s41401-020-0382-x
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