Berberine inhibits low shear stress-induced vascular endothelial inflammation via decreasing phosphorylation of Akt and IRF3

• DOI: 10.1016/j.tice.2022.101946
• Publication Date: 2022-09-23T08:04:32Z
• Authors: Yifei Lv; Hongfeng Yang; Peng Ye; Zhiyuan Qian; Dongchen Wang; Chaohua Kong; Yue Gu; Wenying Zhou; Shaoliang Chen; Linlin Zhu
• Keywords: VCAM-1

Abstract Background Low shear stress (LSS) is closely related to vascular endothelial inflammation and the development of atherosclerosis. Berberine (BBR), a natural compound isolated from Coptis chinensis, has been reported to exert anti-inflammatory and anti-atherosclerotic effects. However, the role of berberine in low-shear stress-induced endothelial inflammation remains unclear. Methods The role of berberine in low shear stress-induced vascular endothelial inflammation was investigated in human umbilical vein endothelial cells (HUVECs) using a plate flow chamber in vitro and in mice with an established LSS model by partial ligation of the carotid artery in vivo. Results Firstly, in vitro experiments demonstrated that BBR significantly decreased the expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) and the phosphorylation of Akt in HUVECs induced by low shear stress.Meanwhile,BBR significantly inhibited low shear stress induced IRF3 phosphorylation and nuclear translocation. Notably, Akt overexpression markedly reversed the inhibitory effects of BBR on LSS-induced IRF3 activation and ICAM-1 expression. Moreover, in vivo experiments showed that BBR markedly decreased intimal ICAM-1 and IRF3 in the LSS areas of partially ligated carotid arteries in mice; however, EC-specific Akt overexpression mediated by adeno-associated virus abolished the anti-inflammatory effect of BBR. Conclusion Taken together, our findings suggest that BBR treatment attenuates LSS-induced vascular endothelial inflammation by decreasing activation of the Akt/IRF3 signalling pathway.