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Salidroside Ameliorates Ischemia/Reperfusion-Induced Human Cardiomyocyte Injury by Inhibiting the Circ_0097682/miR-671-5p/USP46 Pathway

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Abstract

Salidroside shows an inhibitory effect on myocardial ischemia/reperfusion (I/R) injury; however, the underlying mechanism remains to be explored. The present work analyzes the mechanism that drives salidroside to ameliorate I/R-induced human cardiomyocyte injury. Human cardiomyocytes were subjected to I/R treatment to simulate a myocardial infarction cell model. Cell viability, cell proliferation, and cell apoptosis were analyzed by CCK-8 assay, EdU assay, and flow cytometry analysis, respectively. RNA expression levels of circ_0097682, miR-671-5p, and F-box and ubiquitin-specific peptidase 46 (USP46) were detected by qRT-PCR. Protein expression was measured by Western blotting assay. The levels of IL-6, IL-1β, and TNF-α in cell supernatant were detected by enzyme-linked immunosorbent assays. Salidroside treatment relieved I/R-induced inhibitory effect on AC16 cell proliferation and promoting effects on cell apoptosis, inflammation, and oxidative stress. Salidroside inhibited circ_0097682 expression in I/R-treated AC16 cells. Salidroside-mediated inhibition of I/R-induced cell injury involved the downregulation of circ_0097682 expression. In addition, circ_0097682 bound to miR-671-5p in AC16 cells, and miR-671-5p inhibitors rescued salidroside pretreatment-mediated effects in I/R-treated AC16 cells. Moreover, miR-671-5p targeted USP46 in AC16 cells, and USP46 introduction partially relieved circ_0097682 depletion or salidroside pretreatment-induced effects in I/R-treated AC16 cells. Salidroside ameliorated I/R-induced AC16 cell injury by inhibiting the circ_0097682/miR-671-5p/USP46 pathway.

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Funding

This work was supported by Experimental study on the effect of salidroside on diabetes rats with coronary heart disease. Hebei Provincial Department of Health Project (20130062).

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Authors and Affiliations

  1. College of Traditional Chinese Medicine, North China University of Science Technology, Qinhuangdao, China

    Yuyang Yang, Jian Li, Chunhua Jiang, Wei Xie, Shujuan Wu, Ya Wang & Jing Yi

  2. Department of General Practice, North China University of Science and Technology Affiliated Hospital, No. 73, Jianshe South Road, Lubei District, Tangshan, 063000, Hebei, China

    Fangqian Liang & Jingyuan Gao

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  1. Yuyang Yang
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Contributions

YY: designed and performed the research; FL, JG, JL, CJ, WX, SW, YW, and JY: analyzed the data; YY: wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jingyuan Gao.

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Yang, Y., Liang, F., Gao, J. et al. Salidroside Ameliorates Ischemia/Reperfusion-Induced Human Cardiomyocyte Injury by Inhibiting the Circ_0097682/miR-671-5p/USP46 Pathway. Cardiovasc Toxicol 23, 406–418 (2023). https://doi.org/10.1007/s12012-023-09808-3

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