An Evidence Update to Explore Molecular Targets and Protective Mechanisms of Apigenin against Abdominal Aortic Aneurysms Based on Network Pharmacology and Experimental Validation

Abstract

AbstractAbdominal aortic aneurysms(AAA) is a life-threatening disease and the incidence of AAA is still on the rise in recent years. Numerous studies suggest dietary moderate consumption of polyphenol exert beneficial effects on cardiovascular disease. Apigenin(API) is a promising dietary polyphenol and possesses potent beneficial effects on our body. Although our previous study revealed protective effects of API on experimental AAA formation, up till now few studies were carried out to further investigate its involved molecular mechanisms. In the present study, network pharmacology combined molecular docking and experimental validation was used to explore API-related therapeutic targets and mechanisms in the treatment of AAA. Firstly, we collected 202 API-related therapeutic targets and 2475 AAA-related pathogenetic targets. After removing duplicates, a total of 68 potential therapeutic targets were obtained. Moreover, 5 targets with high degree including TNF, ACTB, INS, JUN and MMP9 were identified as core targets of API for treating AAA. In addition, functional enrichment analysis indicated API exerted pharmacological effects in AAA by affecting versatile mechanisms, including apoptosis, inflammation, blood fluid dynamics and immune modulation. Molecular docking results further supported that API had strong affinity with the above core targets. Furthermore, protein level of core targets and related pathways were evaluated in a Cacl2-induced AAA model by using western blot and immunohistochemistry. The experimental validation results demonstrated that API significantly attenuated phosphorylation of JUN and protein level of predicted core targets. Taken together, based on network pharmacological and experimental validation, our study systematically explored associated-core targets and potential therapeutic pathways of API for AAA treatment, which could supply valuable insights and theoretical basis for AAA treatment.