Exploring the Effect and Mechanism of Si-Miao-Yong-An Decoction on Abdominal Aortic Aneurysm Based on Mice Experiment and Bioinformatics Analysis

基于小鼠实验及生物信息学分析探讨四妙勇安汤治疗腹主动脉瘤的疗效及机制

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作者:Zhenyu Xu, Lulu Zhang, Ning Huangfu, Fengchun Jiang, Kangting Ji, Shenghuang Wang

Background

Abdominal aortic aneurysm (AAA) is a fatal disease characterized by high morbidity and mortality in old population. Globally, effective drugs for AAA are still limited. Si-Miao-Yong-An decoction (SMYAD), a traditional Chinese medicine (TCM) formula with a high medical value, was reported to be successfully used in an old AAA patient. Thus, we reason that SMYAD may serve as a potential anti-AAA regime.

Conclusion

SMYAD can suppress AAA development through multicompound, multitarget, and multipathway, which provides a research direction for further study.

Methods

Firstly, C57BL/6N mice induced by Bap and Ang II were utilized to reproduce the AAA model, and the effects of SMYAD were systematically assessed according to histology, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). Then, network pharmacology was applied to identify the biological processes, pathways, and hub targets of SMYAD against AAA; moreover, molecular docking was utilized to identify the binding ability and action targets.

Objective

The exact effects and detailed mechanisms of SMYAD on AAA were explored by using the experimental study and bioinformatics analysis.

Results

In an animal experiment, SMYAD was found to effectively alleviate the degree of pathological expansion of abdominal aorta and reduce the incidence of Bap/Ang II-induced AAA, along with reducing the damage to elastic lamella, attenuating infiltration of macrophage, and lowering the circulating IL-6 level corresponding to the animal study, and network pharmacology revealed the detailed mechanisms of SMYAD on AAA that were related to pathways of inflammatory response, defense response, apoptotic, cell migration and adhesion, and reactive oxygen species metabolic process. Then, seven targets, IL-6, TNF, HSP90AA1, RELA, PTGS2, ESR1, and MMP9, were identified as hub targets of SMYAD against AAA. Furthermore, molecular docking verification revealed that the active compounds of SMYAD had good binding ability and clear binding site with core targets related to AAA formation.

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