An integrative approach for mechanistic insights into the atherosclerotic plaque-stabilizing properties of Danggui Buxue decoction.

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Tác giả: Xiangyang Cao, Yan Ji, Yi Jing, Heng Li, Yingying Shi, Ling Wang, Yunpeng Wang, Qingping Xiong, Ruixue Yan, Yadong Yu, Yuhan Zhang, Guangzhen Zheng

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: Ireland : Journal of ethnopharmacology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 731810

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Buxue Decoction (DBD), a traditional Chinese medicinal formula, has historically been used for cardiovascular health, including managing atherosclerotic plaques (ASP). However, its precise mechanisms remain elusive. AIM OF THE STUDY: The purpose of this study was to use a novel integrative bioinformatics analysis and experimental validation approach to provide a molecular basis for ASP's stabilization by DBD. MATERIALS AND METHODS: A mice model of ApoE-deficient atherosclerosis fed with a high-fat diet was employed to evaluate the efficacy of DBD in stabilizing ASP. The potential mechanism underlying the stabilization effect of DBD on ASP was systematically investigated using an integrated approach combining network pharmacology, molecular docking, and molecular dynamics simulation. Additionally, an ox-LDL-induced macrophage foam cell model and multivariate statistical analysis were utilized to validate the pharmacodynamic material basis and target of DBD in stabilizing ASP. RESULTS: Firstly, it was found that DBD can significantly alleviate ASP, which was manifested as a significant reduction in the atherosclerosis index, ratio of area for plaque to lumen, and vulnerability index. Afterwards, network pharmacology investigation identified quercetin and kaempferol as the primary active compounds in DBD anti-ASP. Key core targets mainly involved TP53, AKT1, IL-6 and TNF. The main action pathways included lipid and atherosclerosis, PI3K-Akt signaling, and other pathways. Subsequently, molecular docking and molecular dynamics simulation results confirmed the strong stability of the main active compounds with the key target. Finally, the cell validation experiment in vitro revealed that both quercetin and kaempferol could significantly inhibit RAW264.7 macrophage foaming formation induced by ox-LDL and improve its lipid metabolism disorder. Meanwhile, they could also significantly reverse ox-LDL induced abnormal expression of core protein predicted by network pharmacology in RAW264.7 foam cells. Further correlation analysis revealed that the improvement effect of quercetin and kaempferol on macrophage foaming had a close correlation with the inhibition of core protein expression. CONCLUSION: DBD mainly utilized active ingredients such as quercetin and kaempferol, through regulating multiple targets like TP53, AKT1, IL-6 and TNF, to stabilize ASP.
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