The Lian-Dou-Qing-Mai formula activates the PPARγ-LXRα-ABCA1/ABCG1 pathway by regulating IL-10, leading to the promotion of cholesterol efflux and a reduction in atherosclerotic plaques

Abstract

Background. To observe the effect of the Lian-Dou-Qing-Mai (LDQM) formula on lipid metabolism in mice and explore its mechanism from the perspective of regulating the PPARγ/LXRα/ABCA1 signaling pathway. Methods. THP-1 cells were induced to transform into foam cells with ox-LDL. Atherosclerosis (AS) models were constructed using a high-fat diet in ApoE-/- mice. Detection kits were used to evaluate triglyceride (TG) and total cholesterol (TC) content; TNF-α, MCP-1, MMP-9, TMP-1, PPARγ, LXRα, ABCA1, and ABCG1 mRNA and protein expression were identified using real-time PCR and western blot. Aortic plaque development and lipid deposition were seen using hematoxylin and eosin (HE) and oil red O staining, respectively. Results. In the cell model, LDQM could inhibit the formation of THP-1 macrophage-derived foam cells and the expression of inflammatory factors, promote macrophage cholesterol efflux, increase the expression of IL-10, and activate the PPARγ-LXRα-ABCA1/ ABCG1 pathway. Additional IL-10 treatment further promotes LDQM-induced cholesterol efflux in THP-1 cells. In in vivo models, LDQM inhibited the area of atherosclerotic lesions, aortic lipid deposition, and inflammation levels in ApoE-/- mice through IL-10, and activated the expression level of the PPARγ-LXRα-ABCA1/ABCG1 pathway. Conclusion. LDQM may affect the PPARγ/LXRα/ ABCA1 signaling pathway through IL-10, regulate lipid metabolism, reduce serum inflammatory expression and lipid deposition, and improve the formation of atheroplaques.