Integrating Network Pharmacology and Experimental Validation to Investigate the Action Mechanism of Allicin in Atherosclerosis

整合网络药理学和实验验证以研究大蒜素在动脉粥样硬化中的作用机制

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Abstract

BACKGROUND: Allicin is a monomer compound derived from traditional Chinese medicine, which has demonstrated significant efficacy in the treatment of cancer, neuroinflammation, gastrointestinal diseases, and other conditions. However, the specific mechanism of action of Allicin in combating cardiovascular diseases remains insufficiently clarified, which limits its application in therapy. METHODS: Network pharmacology and molecular docking techniques were employed to explore the potential targets and signaling pathways of Allicin in the treatment of as atherosclerosis (AS). The regulatory effects of Allicin on cell apoptosis, aortic plaques, and lipid levels were assessed through TUNEL staining, Oil Red O staining, HE staining, GPO-PAP, and COD-PAP. Additionally, immunofluorescence assay was conducted to validate the screened key targets. RESULTS: Based on the analysis of network pharmacology and molecular docking techniques, 94 predicted overlapping target genes were identified from the target genes of Allicin and AS-related target genes; Among them, Allicin exhibits a strong binding affinity for five main targets (CASP3, NF-κB1, BTK, MAPK3, and PARP1), and these targets were found to play important role in the anti-apoptotic mechanism of Allicin. Furthermore, Allicin could inhibit the progression of plaques, down- regulating the expressions of CASP3 and NF-κB1, and up-regulate the expressions of BTK, MAPK3, and PARP1 in vivo and in vitro. CONCLUSION: The present results show that Allicin may improves AS by regulating the main targets of macrophage apoptosis.

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