The Molecular Mechanisms of Bergapten Against Abdominal Aortic Aneurysm: Evidence From Network Pharmacology,...

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.