Li Dongyu, Wang Lei, Jiang Bo, Miao Yuxi, Li Xuan
Department of General Surgery & VIP In-Patient Ward, The First Hospital of China Medical University, Shenyang, 110001, Liaoning Province, China.
Department of Vascular and Thyroid Surgery, The First Hospital of China Medical University, Nanjingbei 155 Street, Shenyang, 110001, Liaoning Province, China.
Mol Divers. 2024 Oct;28(5):2913-2929. doi: 10.1007/s11030-023-10723-6. Epub 2023 Aug 31.
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 that dietary moderate consumption of polyphenol exerts 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 that 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.
腹主动脉瘤（AAA）是一种危及生命的疾病，近年来AAA的发病率仍在上升。大量研究表明，饮食中适度摄入多酚对心血管疾病具有有益作用。芹菜素（API）是一种很有前景的膳食多酚，对我们的身体具有强大的有益作用。尽管我们之前的研究揭示了API对实验性AAA形成的保护作用，但到目前为止，很少有研究进一步探讨其相关的分子机制。在本研究中，采用网络药理学结合分子对接和实验验证的方法，探索API治疗AAA的相关治疗靶点和机制。首先，我们收集了202个与API相关的治疗靶点和2475个与AAA相关的致病靶点。去除重复项后，共获得68个潜在治疗靶点。此外，确定了包括TNF、ACTB、INS、JUN和MMP9在内的5个高度相关靶点为API治疗AAA的核心靶点。此外，功能富集分析表明，API通过影响多种机制在AAA中发挥药理作用，包括细胞凋亡、炎症、血液动力学和免疫调节。分子对接结果进一步支持API与上述核心靶点具有很强的亲和力。此外，通过蛋白质印迹法和免疫组织化学法在Cacl2诱导的AAA模型中评估核心靶点的蛋白水平和相关通路。实验验证结果表明，API显著减弱了JUN的磷酸化和预测核心靶点的蛋白水平。综上所述，基于网络药理学和实验验证，我们的研究系统地探索了API治疗AAA的相关核心靶点和潜在治疗途径，可为AAA治疗提供有价值的见解和理论依据。
