Front Cardiovasc Med. 2026 Sep 22;13:1896890. doi: 10.3389/fcvm.2026.1896890. eCollection 2026.
ABSTRACT
BACKGROUND: Atherosclerosis (AS) is a major contributor to deaths from cardiovascular diseases. Yiqihuoxue Formula (YQHXF) reflects the traditional Chinese medicine principle of "Qi-invigorating and blood-activating." This study investigates the anti-atherosclerotic effects and mechanism of YQHXF through the signal transducer and activator of transcription 6 (STAT6)/ peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathway and macrophage polarization.
METHODS: Ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) was used to detect the components of YQHXF-containing serum (YQHXF-CS). Using oxidized low-density lipoprotein (ox-LDL), RAW264.7 macrophages were induced into foam cells in vitro and treated with YQHXF-CS. PPARγ knockdown was achieved using siRNA. Cell viability, lipid accumulation, macrophage polarization markers, and STAT6/PPARγ signaling were analyzed. In vivo, ApoE-/- mice fed a high-fat diet (HFD) received low, medium, or high-dose YQHXF or atorvastatin. Serum lipids, aortic plaque area, histopathology, macrophage polarization, and pathway proteins were assessed.
RESULTS: The results showed that YQHXF-CS contained 2,317 components. In vitro, 5% YQHXF-CS enhanced cell viability, reduced lipid droplets, downregulated M1 markers (nitric oxide synthase 2 (Nos2), tumor necrosis factor (Tnf), interleukin 1 beta (Il1b)), upregulated M2 markers (interleukin 4 (Il4), arginase 1 (Arg1), transforming growth factor-β (Tgfb), CD163, CD206), and this was accompanied by enhanced STAT6/PPARγ pathway. Moreover, YQHXF-CS partially counterbalanced siRNA-PPARγ-induced foam cells formation, and this effect was associated with M2 macrophages polarization. In vivo, YQHXF reduced body weight and serum lipid accumulation, diminished aortic plaque area and pathological damage, increased M2 macrophages (CD206+, IL-4, IL-10), and decreased M1 macrophages (CD86+, TNF-α, IL-1β). Mechanistically, YQHXF partially restored aortic p-STAT6 and PPARγ expression.
CONCLUSIONS: YQHXF ameliorates AS, as evidenced by reduced foam cell formation, alleviated vascular lesions, and promotion of anti-inflammatory M2 macrophage polarization; these effects were associated with enhanced STAT6/PPARγ signaling. This validates the theory of "Qi-invigorating and blood-activating" and highlights YQHXF's therapeutic potential.
PMID:42839935 | PMC:PMC13638390 | DOI:10.3389/fcvm.2026.1896890