Mechanism of Tao Hong Decoction in the treatment of atherosclerosis based on network pharmacology and experimental validation

Background: Atherosclerosis (AS) has long been recognized as a cardiovascular disease and stroke risk factor. A well-known traditional Chinese medicine prescription, Tao Hong decoction (THD), has been proven effective in treating AS, but its mechanism of action is still unclear. Objective: To assess the effects, explore THD's primary mechanism for treating AS, and provide a basis for rational interpretation of its prescription compatibility. Methods: Based on network pharmacology, we evaluated the mechanism of THD on AS by data analysis, target prediction, the construction of PPI networks, and GO and KEGG analysis. AutoDockTools software to conduct Molecular docking. Then UPLC-Q-TOF-MS was used to identify significant constituents of THD. Furthermore, an AS mice model was constructed and intervened with THD. Immunofluorescence, RT-qPCR, and Western blot were used to verify the critical targets in animal experiments. Results: The network pharmacology results indicate that eight core targets and seven core active ingredients play an essential role in this process. The GO and KEGG analysis results suggested that the mechanism is mainly involved in Fluid shear stress and atherosclerosis and Lipid and atherosclerosis. The molecular docking results indicate a generally strong affinity. The animal experiment showed that THD reduced plaque area, increased plaque stability, and decreased the levels of inflammatory cytokines (NF-κB, IL-1α, TNF-α, IL-6, IL-18, IL-1β) in high-fat diet -induced ApoE-/-mice. Decreased levels of PTGS2, HIF-1α, VEGFA, VEGFC, FLT-4, and the phosphorylation of PI3K, AKT, and p38 were detected in the THD-treated group. Conclusion: THD plays a vital role in treating AS with multiple targets and pathways. Angiogenesis regulation, oxidative stress regulation, and immunity regulation consist of the crucial regulation cores in the mechanism. This study identified essential genes and pathways associated with the prognosis and pathogenesis of AS from new insights, demonstrating a feasible method for researching THD's chemical basis and pharmacology.