Bergenin alleviates proliferative arterial diseases by modulating glucose metabolism in vascular smooth muscle cells

Yujie Song; Meng Deng; Yufeng Qiu; Yang Cui; Bing Zhang; Jialin Xin; Lele Feng; Xingdou Mu; Jun Cui; Hong Li; Yang Sun; Wei Yi

doi:10.1016/j.phymed.2024.155592

Bergenin alleviates proliferative arterial diseases by modulating glucose metabolism in vascular smooth muscle cells

Phytomedicine. 2024 Apr 6:129:155592. doi: 10.1016/j.phymed.2024.155592. Online ahead of print.

Authors

Yujie Song¹, Meng Deng², Yufeng Qiu², Yang Cui¹, Bing Zhang¹, Jialin Xin¹, Lele Feng¹, Xingdou Mu², Jun Cui¹, Hong Li², Yang Sun³, Wei Yi⁴

Affiliations

¹ Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an 710000, China.
² Department of General Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an 710000, China.
³ Department of General Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an 710000, China. Electronic address: drsunyang@fmmu.edu.cn.
⁴ Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an 710000, China,. Electronic address: yiwei@fmmu.edu.cn.

PMID: 38608597
DOI: 10.1016/j.phymed.2024.155592

Abstract

Background: Vascular smooth muscle cell (VSMC) proliferation and phenotypic switching are key mechanisms in the development of proliferative arterial diseases. Notably, reprogramming of the glucose metabolism pattern in VSMCs plays an important role in this process.

Purpose: The aim of this study is to investigate the therapeutic potential and the mechanism underlying the effect of bergenin, an active compound found in Bergenia, in proliferative arterial diseases.

Methods: The effect of bergenin on proliferative arterial disease was evaluated using platelet-derived growth factor (PDGF)-stimulated VSMCs and a mouse model of carotid artery ligation. VSMC proliferation and phenotypic switching were evaluated in vitro using cell counting kit-8, 5-ethynyl-2-deoxyuridine incorporation, scratch, and transwell assays. Carotid artery neointimal hyperplasia was evaluated in vivo using hematoxylin and eosin staining and immunofluorescence. The expression of proliferation and VSMC contractile phenotype markers was evaluated using PCR and western blotting.

Results: Bergenin treatment inhibited PDGF-induced VSMC proliferation and phenotypic switching and reduced neointimal hyperplasia in the carotid artery ligation model. Additionally, bergenin partially reversed the PDGF-induced Warburg-like glucose metabolism pattern in VSMCs. RNA-sequencing data revealed that bergenin treatment significantly upregulated Ndufs2, an essential subunit of mitochondrial complex I. Ndufs2 knockdown attenuated the inhibitory effect of bergenin on PDGF-induced VSMC proliferation and phenotypic switching, and suppressed neointimal hyperplasia in vivo. Conversely, Ndufs2 overexpression enhanced the protective effect of bergenin. Moreover, Ndufs2 knockdown abrogated the effects of bergenin on the regulation of glucose metabolism in VSMCs.

Conclusion: These findings suggest that bergenin is effective in alleviating proliferative arterial diseases. The reversal of the Warburg-like glucose metabolism pattern in VSMCs during proliferation and phenotypic switching may underlie this therapeutic mechanism.

Keywords: Bergenin; Glycolysis; Neointima formation; Oxidative phosphorylation; Vascular smooth muscle cell.