WITHDRAWN: Deciphering mechanism of Buyang Huanwu Decoction in regulating macrophage polarization to alleviate atherosclerosis via virtual screening and experimental verification

ETHNOPHARMACOLOGICAL RELEVANCE: Buyang Huanwu Decoction (BYHWD), a traditional prescription known for its Supplementing Qi and Promoting Blood Circulation, has demonstrated noteworthy therapeutic roles in regulating macrophage polarization to atherosclerosis (AS). However, its underlying mechanisms remain unknown. AIM OF THE STUDY: The purpose of this paper was to decipher mechanism of BYHWD in regulating macrophage polarization to alleviate AS. MATERIALS AND METHODS: A comprehensive virtual screening strategy, incorporating network pharmacology and batch molecular docking, combined with experimental validation techniques, was employed to systematically elucidate the underlying mechanism of BYHWD regulating macrophage polarization to alleviate AS. RESULTS: Firstly, based on high-fat diet induced AS model in apolipoprotein E-deficient mice, it was found that BYHWD can significantly regulate macrophage polarization to alleviate AS. Then, the network pharmacological analysis revealed that the core targets of BYHWD regulating macrophage polarization to alleviate AS mainly involved TP53, AKT1 and BCL2. The mitochondrial function and metabolism were the main biological processes. Meanwhile, the main chemical components were identified as 3-O-p-coumaroylquinic acid, D-mandelonitrile, Ellagic acid, Ferulic acid, 5-hydroxy-L-tryptophan zwitterion, Isoliquiritigenin, Senkyunolide-F, Anofinic acid, Trimethylhydroquinone and Senkyunolide-E by batch molecular docking strategy. Further, the in vitro experiments demonstrated that BYHWD not only regulated macrophage polarization and alleviated macrophage foam formation but also modulated mitochondrial function and the expression of TP53, p-AKT, and BCL2 proteins. Finally, multivariate statistical analysis confirmed that the ameliorative effect of BYHWD on AS was closely related to mitochondrial function and macrophage polarization regulated by TP53, AKT1 and BCL2. CONCLUSIONS: BYHWD could activate key targets, including TP53, AKT1, and BCL2, to alleviate mitochondrial dysfunction and regulate macrophage polarization, thereby improving AS. The 10 active compounds of BYHWD, including 5-hydroxy-L-tryptophan zwitterion and Isoliquiritigenin, played an important role in regulating macrophages polarization to alleviate AS.