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The Berberis vulgaris L. extract berberine exerts its anti-oxidant effects to ameliorate cholesterol overloading–induced cell apoptosis in the primary mice hepatocytes: an in vitro study

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Abstract

Cholesterol overloading stress damages normal cellular functions in hepatocytes and induces metabolic disorders to facilitate the development of multiple diseases, including cardiovascular diseases, which seriously degrades the life quality of human beings. Recent data suggest that the Berberis vulgaris L. extract berberine is capable of regulating cholesterol homeostasis, which is deemed as potential therapeutic drug for the treatment of cholesterol overloading–associated diseases, but its detailed functions and molecular mechanisms are still largely unknown. In the present study, we evidenced that berberine suppressed cell apoptosis in high-cholesterol-diet mice liver and cholesterol-overloaded mice hepatocytes. Also, cholesterol overloading promoted reactive oxygen species (ROS) generation to trigger oxidative damages in hepatocytes, which were reversed by co-treating cells with both berberine and the ROS scavenger N-acetylcysteine (NAC). Moreover, the underlying mechanisms were uncovered, and we validated that berberine downregulated Keap1, and upregulated Nrf2 to activate the anti-oxidant Nrf2/HO-1 signaling pathway in cholesterol overloading–treated hepatocytes, and both Keap1 upregulation and Nrf2 downregulation abrogated the suppressing effects of berberine on cell apoptosis in the hepatocytes with cholesterol exposure. Taken together, we concluded that berberine activated the anti-oxidant Keap1/Nrf2/HO-1 pathway to eliminate cholesterol overloading–induced oxidative stress and apoptotic cell death in mice hepatocytes, and those evidences hinted that berberine might be used as putative therapeutic drug for the treatment of cholesterol overloading–associated cardiovascular diseases.

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Data availability statement

All the involved data had been included in the manuscript, and the original data could be obtained from the corresponding author upon reasonable request.

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Funding

This study was financially supported by Basic Research Program of Yunnan Science and Technology Department (Joint Specialized Project of Kunming Medical University, No. 202101AY070001-085) and the Doctoral Research Fund of First Affiliated Hospital of Kunming Medical University (No. 2018BS006).

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, First Affiliated Hospital of Kunming Medical University, Xichang Road No. 295, Kunming, 650032, Yunnan Province, China

    Zhengchen Ye, Qiang Wang, Shupeng Dai, Xiang Ji, Pingli Cao, Chenglei Xu & Guoqing Bao

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  1. Zhengchen Ye
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  2. Qiang Wang
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  3. Shupeng Dai
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  4. Xiang Ji
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  7. Guoqing Bao
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Contributions

Zhengchen Ye conducted most of the investigations, drafted the manuscript, and was the main author of this manuscript. Qiang Wang, Shupeng Dai, Xiang Ji, Pingli Cao, and Chenglei Xu were co-authors; they provided technical supports, and helped to analyze and visualize the data. Guoqing Bao was the corresponding author of this work, and was responsible for conception, guidance, manuscript proofreading, and funding acquisition.

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Correspondence to Guoqing Bao.

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All the experiments in the present study were approved by the guidelines of the Ethics Committee affiliated to our hospital (No. KMMU2020495) in August 17, 2020.

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Ye, Z., Wang, Q., Dai, S. et al. The Berberis vulgaris L. extract berberine exerts its anti-oxidant effects to ameliorate cholesterol overloading–induced cell apoptosis in the primary mice hepatocytes: an in vitro study. In Vitro Cell.Dev.Biol.-Animal 58, 855–866 (2022). https://doi.org/10.1007/s11626-022-00737-z

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