Candidate Targets of Dan-Lou Tablets in Hyperlipidemia-Associated Coronary Heart Disease
Xiaofei Sun, Jing Lin, Chen Liang, Jingjing Liu, Meixiu Jiang, Fangfang Liu, Pengzhi DongAbstract
Coronary heart disease (CHD) is closely associated with dyslipidemia-driven atherosclerosis, in which macrophage-mediated inflammation links lipid deposition to plaque progression. Dan-Lou tablets (DLT), a traditional Chinese medicine preparation used clinically for CHD, have been reported to affect lipid and inflammatory pathways. This study aimed to identify candidate targets and pathways of blood-absorbed DLT constituents in hyperlipidemia-associated CHD and macrophage-associated inflammatory contexts.
Six blood-absorbed constituents of DLT (puerarin, formononetin, calycosin, paeoniflorin, tanshinone IIA, and cryptotanshinone) were investigated using an integrated network pharmacology and public transcriptomic strategy. Compound-related targets from TCMSP were intersected with hyperlipidemia-related genes from GeneCards, followed by enrichment analysis, protein-protein interaction analysis, macrophage-infiltration correlation analysis, GeneMANIA network analysis, and validation using the Gene Expression Omnibus dataset GSE179789.
A total of 117 compound targets and 3,449 hyperlipidemia-related genes yielded 79 intersecting genes. Enrichment analysis highlighted lipid and atherosclerosis, interleukin signaling, fluid shear stress and atherosclerosis, AGE-RAGE signaling, hormone-related responses, and JAK-STAT-related pathways. Twenty-two genes showed relatively strong associations with inferred macrophage infiltration in the exploratory TCGA-LIHC analysis. CAV1, PTGIS, KLF9, and BCL2 showed differential expression in peripheral blood mononuclear cells from CHD patients before and after DLT treatment in GSE179789.
DLT may influence hyperlipidemia-associated CHD through candidate targets linked to lipid metabolism and macrophage-associated inflammatory pathways. Because the present work is based mainly on in silico prediction and public-dataset validation, the findings should be regarded as hypothesis-generating and require further experimental validation, particularly direct assessment of macrophage phenotype and function.