Exploring potential mechanism of Chuanzhi Qingyu recipe for vulnerable atherosclerosis plaques based on UPLC-Q-TOF-MS, systems biology strategy, and experimental validation.

Abstract

Chuanzhi Qingyu (CZQY) recipe is clinically used for the secondary prevention and treatment of cardiovascular diseases associated with atherosclerosis (AS) However, the potential active components and underlying molecular mechanisms require further elucidation. This study established a mouse model of vulnerable AS plaques through a high-fat diet. The efficacy of CZQY in stabilizing these vulnerable plaques was assessed using histological staining techniques. Additionally, biochemical analyses, ELISA assays, small animal ultrasound technology, and immunohistochemistry were employed. Subsequently, the active pharmaceutical ingredients of CZQY were identified through UPLC-Q-TOF-MSE. Finally, a network pharmacology approach, in conjunction with RNA-seq was utilized to predict the targets and mechanisms of CZQY in stabilizing vulnerable AS plaques, which were subsequently validated using Western blot and PCR methods. The research results show that CZQY can significantly improve lipid levels and liver function, reduce serum inflammation and oxidative stress levels, improve vascular function, and stabilize vulnerable AS plaques. The main components of CZQY that stabilize vulnerable AS plaques include flavonoids, terpenoids, and organic acids. The findings from RNA-seq and network pharmacology suggest that CZQY stabilizes vulnerable AS plaques potentially through mechanisms related to lipid metabolism, inflammatory responses, and cell migration, etc. Subsequent RT-qPCR and Western blot analyses confirmed that CZQY significantly modulated the expression of key targets at both mRNA and protein levels. In conclusions, CZQY effectively reduces risk factors associated with vulnerable AS plaques, improves vascular function, and stabilizes these plaques. This may be related to its ability to modulate mechanisms involving lipid metabolism, inflammation, extracellular matrix dynamics, and smooth muscle cell phenotype. These findings provide significant data support for further pharmacological research and clinical applications.