Yiqi Wenyang decoction protects against the development of atherosclerosis by inhibiting vascular inflammation

Vascular inflammation is a key process in the pathogenesis of atherosclerosis, which is regulated by NF-κB pathway. Yiqi Wenyang decoction (YQWY), a Traditional Chinese medicine (TCM) formula, has anti-inflammatory properties and may inhibit this pathway, potentially offering anti-atherosclerotic effects. The purpose of this study is to investigate the effects of YQWY on atherosclerosis and the underlying mechanism. Materials and methods: ApoE−/− mice were fed a Western diet and administered with YQWY (low or high dose), atorvastatin, or vehicle for 13 weeks. The size of atherosclerotic plaques was assessed using ORO staining. Vascular inflammation was evaluated with IF or IHC staining. The mechanisms and signaling pathways underlying the effect of YQWY on vasculature were studied using transcriptomic analysis and were validated in vitro in endothelial cells and macrophages. YQWY attenuated atherosclerotic plaque development which was associated with reduced vascular inflammation as demonstrated by transcriptomic analysis of aorta. This was verified by reduced expression of proinflammatory chemokines, adhesion molecules, and inflammatory cytokines in aortas from YQWY-treated mice at both mRNA and protein levels. Mechanistically, YQWY suppressed NF-κB activation in endothelial cells and, to a lesser extent, macrophages possibly. YQWY protects against vascular inflammation and atherosclerosis by suppressing NF-κB pathway, suggesting the potential of YQWY and its active ingredients as novel anti-atherosclerotic therapeutics.

血管炎症是动脉粥样硬化发病机制中的关键过程，该过程受NF-κB通路调控。益气温阳汤（Yiqi Wenyang decoction, YQWY）作为一种中医药（Traditional Chinese Medicine, TCM）方剂，具备抗炎特性，可抑制该通路，潜在发挥抗动脉粥样硬化作用。本研究旨在探讨益气温阳汤对动脉粥样硬化的作用及其潜在机制。
材料与方法：将ApoE−/−小鼠喂食西方饮食，并分别给予低、高剂量益气温阳汤、阿托伐他汀或空白溶媒，持续13周。采用油红O（Oil Red O, ORO）染色评估动脉粥样硬化斑块面积；采用免疫荧光（Immunofluorescence, IF）或免疫组化（Immunohistochemistry, IHC）染色评估血管炎症程度。通过转录组学分析探讨益气温阳汤对血管作用的潜在机制及信号通路，并在内皮细胞与巨噬细胞中开展体外验证。
主动脉转录组学分析结果显示，益气温阳汤可减轻动脉粥样硬化斑块形成，该效应与血管炎症缓解相关。经益气温阳汤处理的小鼠主动脉组织中，促炎趋化因子、黏附分子及炎症细胞因子的mRNA与蛋白表达水平均显著降低，进一步验证了上述结论。
从机制层面来看，益气温阳汤可抑制内皮细胞中的NF-κB活化，在一定程度上也可能抑制巨噬细胞中的NF-κB活化。
益气温阳汤通过抑制NF-κB通路发挥抗血管炎症与动脉粥样硬化的作用，提示其及其活性成分有望成为新型抗动脉粥样硬化治疗药物。