To explore potential therapeutic targets and underlying mechanisms of apigenin (API) for papillary thyroid carcinoma (PTC) treatment. Methods: In the present study, network pharmacological analysis combined with molecular docking was used to identify API-related therapeutic targets for PTC treatment. Firstly, potential API-interacting and PTC-related targets were obtained from online databases. Furthermore, we constructed drug-target-disease interaction networks followed by functional enrichment analysis, expression patterns and prognostic values of predicted core targets by using bioinformatic tools. Moreover, we performed molecular docking to validate binding activity of API to core pharmacological targets. Results: A total of 110 API-related therapeutic targets were found to be engaged in the treatment of PTC. Moreover, TP53, HSP90AA1, AKT1, EGFR, SRC, VEGFA, ACTB, JUN and ESR1 were identified as core pharmacological targets of API for treating PTC. The enrichment analysis suggested that API played a comprehensive role in regulating the apoptotic process, modulating cell proliferation, and that multiple pathways were involved in API-related PTC treatment. Further results indicated that the PI3k-Akt/p53 signaling pathway was the key signaling pathway. Moreover, JUN was found mostly correlated with survival and molecular docking results demonstrating strong affinities between API and these core targets. Conclusion: Our findings systematically demonstrated API-associated pharmacological targets and mechanisms for treating PTC and demonstrated that API could function against PTC by inducing apoptosis, cell death and immunological reactions. Our research gives valuable insights and a theoretical basis for API-related PTC treatment.

Abdominal 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.