Xu Fujia, Luo Sihan, Huang Zhenhua, Wang Junfen, Li Tian, Zhong Lintao, Si Xiaoyun
Guizhou Medical University, Guiyang, China.
Department of Emergency Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.
J Cell Biochem. 2025 Apr;126(4):e70029. doi: 10.1002/jcb.70029.
This study endeavors to assess the potential protective role of bergapten (BP) in mitigating abdominal aortic aneurysm (AAA) and to decipher the underlying mechanisms and molecular targets. Network pharmacology was utilized to search for potential targets of BP against AAA. Molecular docking and molecular dynamics simulations were utilized to validate the interaction of BP with core targets, and then the therapeutic effect and mechanism of BP on AAA were verified by using an elastase-induced AAA model. Network pharmacology analysis identified five pharmacological targets for BP, including EGFR, SRC, PIK3CA, PIK3CB, and JAK2. Molecular docking and molecular dynamics simulations further prioritized JAK2 as the most promising candidate for the potential treatment of AAA. The results of animal experiments demonstrated that BP significantly reduced the expression of inflammatory cytokines IL-6, TNF-α, and IL-1β in the aortic tissue of AAA mouse model, and inhibited the phosphorylation of JAK2 and STAT3. BP plays an important role in the treatment of AAA, and it may become a promising drug to combat AAA progression. The inhibitory effect of BP on AAA vascular progression and the attenuation of inflammatory cell infiltration may be related to the regulation of JAK2/STAT3 signaling pathway.
本研究旨在评估补骨脂素（BP）在减轻腹主动脉瘤（AAA）方面的潜在保护作用，并阐明其潜在机制和分子靶点。利用网络药理学寻找BP抗AAA的潜在靶点。采用分子对接和分子动力学模拟验证BP与核心靶点的相互作用，然后通过弹性蛋白酶诱导的AAA模型验证BP对AAA的治疗效果和机制。网络药理学分析确定了BP的五个药理学靶点，包括表皮生长因子受体（EGFR）、原癌基因酪氨酸蛋白激酶（SRC）、磷脂酰肌醇-3激酶催化亚基α（PIK3CA）、磷脂酰肌醇-3激酶催化亚基β（PIK3CB）和 Janus 激酶 2（JAK2）。分子对接和分子动力学模拟进一步将JAK2确定为AAA潜在治疗最有前景的候选靶点。动物实验结果表明，BP显著降低AAA小鼠模型主动脉组织中炎性细胞因子白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的表达，并抑制JAK2和信号转导和转录激活因子3（STAT3）的磷酸化。BP在AAA治疗中起重要作用，可能成为对抗AAA进展的有前景的药物。BP对AAA血管进展的抑制作用和炎性细胞浸润的减轻可能与JAK2/STAT3信号通路的调节有关。
