Bergapten抗腹主动脉瘤的分子机制:来自网络药理学、分子对接/动力学和实验验证的证据

IF 3 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Fujia Xu, Sihan Luo, Zhenhua Huang, Junfen Wang, Tian Li, Lintao Zhong, Xiaoyun Si
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引用次数: 0

摘要

本研究旨在评估伯格加滕(BP)在缓解腹主动脉瘤(AAA)中的潜在保护作用,并揭示其潜在机制和分子靶点。利用网络药理学寻找BP对AAA的潜在靶点,利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,然后利用弹性酶诱导的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5个BP的药理靶点,包括EGFR、SRC、PIK3CA、PIK3CB和JAK2。动物实验结果表明,BP可显著降低AAA小鼠主动脉组织中炎症因子IL-6、TNF-α和IL-1β的表达,抑制JAK2和STAT3的磷酸化。BP在AAA的治疗中起着重要的作用,它可能成为一种有前途的药物来对抗AAA的进展。BP对AAA血管进展和炎症细胞浸润的抑制作用可能与调控JAK2/STAT3信号通路有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Molecular Mechanisms of Bergapten Against Abdominal Aortic Aneurysm: Evidence From Network Pharmacology, Molecular Docking/Dynamics, and Experimental Validation

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.

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来源期刊
Journal of cellular biochemistry
Journal of cellular biochemistry 生物-生化与分子生物学
CiteScore
9.90
自引率
0.00%
发文量
164
审稿时长
1 months
期刊介绍: The Journal of Cellular Biochemistry publishes descriptions of original research in which complex cellular, pathogenic, clinical, or animal model systems are studied by biochemical, molecular, genetic, epigenetic or quantitative ultrastructural approaches. Submission of papers reporting genomic, proteomic, bioinformatics and systems biology approaches to identify and characterize parameters of biological control in a cellular context are encouraged. The areas covered include, but are not restricted to, conditions, agents, regulatory networks, or differentiation states that influence structure, cell cycle & growth control, structure-function relationships.
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