Disrupting atherosclerotic plaque formation via the

doi:10.12122/j.issn.1673-4254.2025.09.02

Abstract

Abstract:

Objective To explore the molecular mechanism of Jiangzhi Huaban Decoction (JZHBD) for improving atherosclerosis through the "qi meridian-blood channels" pathway. Methods ApoE^-/- mouse models of atherosclerosis were established by high-fat diet feeding for 8 weeks, with C57BL/6 mice on a normal diet as the controls. Forty ApoE^-/- mouse models were randomized into model group, low-, medium-, and high-dose JZHBD treatment groups, and atorvastatin treatment group (n=8) for their respective treatments for 8 weeks. The changes in body weight and overall condition of the mice were monitored weekly. After the treatments, serum levels of TC, TG, HDL-C, LDL-C, TBA, ALT, and AST of the mice were measured, pathological changes in the liver and aortic root plaques were examined with HE staining, and lipid accumulation in the liver and aortic wall was assessed using Oil Red O staining. The core molecular mechanism was studied through transcriptomics, and the expressions of the key pathway proteins were confirmed using Western blotting and immunohistochemistry. Results Treatment with JZHBD significantly reduced blood lipid and total bile acid levels, improved liver function and hepatic steatosis, and decreased aortic lipid deposition and plaque area in the mouse models of atherosclerosis. Transcriptomic analysis suggested that the therapeutic mechanism of JZHBD involved reverse cholesterol transport, PPAR signaling, and the inflammatory pathways. In atherosclerotic mice, JZHBD treatment obviously up-regulated hepatic expressions of PPARγ, LXRα, ABCA1, ABCG1, and CYP7A1, down-regulated hepatic expressions of p-p65/p65, IL-6, IL1β in the liver, increased ABCG5 and ABCG8 expressions in the intestines, and decreased ICAM-1 and VCAM-1 expressions in the aortic plaques. Conclusion JZHBD improves atherosclerotic vascular damage and plaque formation possibly by regulating hepatic reverse cholesterol transport and inflammation via modulating the hepatic PPARγ/LXRα/NF-κB signaling pathway.

Key words: atherosclerosis, qi meridian-blood channels, Jiangzhi Huaban Decoction, reverse cholesterol transport, vascular cell adhesion molecules

Hongyang WANG, Wenyi ZHU, Xushen CHEN, Tong ZHANG, Zhiwei CAO, Jin WANG, Bo XIE, Qiang LIU, Xuefeng REN. Disrupting atherosclerotic plaque formation via the "qi meridian-blood channel": mechanism of Jiangzhi Huaban Decoction for regulating hepatic reverse cholesterol transport to improve atherosclerosis[J]. Journal of Southern Medical University, 2025, 45(9): 1818-1829.

Figures/Tables 7

Fig.1 Drug intervention flowchart (A) and changes in body (B) and liver weight (C) of the mice during treatment. *P<0.05, **P<0.01 vs NC group; #P<0.05, ##P<0.01 vs HFD group.

Fig.3 Analysis of differentially expressed genes (DEGs) in mouse aortic transcriptomics. A: Volcano plot of DEGs in HFD group vs control and JZHB groups. B: Venn diagram of reversal genes in HFD group vs control and JZHB groups. C: Modular functional clustering analysis of reversal genes and the visualization of the "key gene-pathway" relationships using Sankey-Bubble plot diagrams.

Fig.4 GO and KEGG functional enrichment analysis. A, B: GO functional enrichment analysis of JZHB against AS. C: KEGG pathway enrichment analysis of JZHB against AS. D: Schematic representation of the regulation of key targets of PPARγ/ LXRα/ NF-κB signaling pathway.

Fig.5 Pathological changes in the liver and aortic tissue of the mice in each group. A: Oil Red O staining of the liver tissues in each group (Original magnification: ×200). B: Oil Red O staining of the aortic tissue in each group. **P<0.01 vs NC group; #P<0.05, ##P<0.01 vs HFD group.

Fig.7 Changes of PPARγ/LXRα/NF-κB signaling pathway proteins in the liver of the mice in each group (Mean±SD, n=3). A: PPARγ, LXRα, ABCA1, ABCG1 and CYP7A1 protein expression in the livers of the mice. B: p65, p-p65, IL-6 and IL-1β protein expressions in the livers of the mice. **P<0.01 vs NC group; #P<0.05, ##P<0.01 vs HFD group.

Fig.8 Changes of ABCG5/G8-related proteins in the intestines of the mice in each group (n=3). **P<0.01 vs NC group, #P<0.05, ##P<0.01 vs HFD group.

Fig.9 Immunohistochemistry for ICAM-1 (A) and VCAM-1 (B) proteins in aortic root plaques of the mice in each group (×100). **P<0.01 vs NC group, #P<0.05, ##P<0.01 vs HFD group.

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