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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

Protective Effects of Liriodendrin on Myocardial Infarction-Induced Fibrosis in Rats via the PI3K/Akt Autophagy Pathway: A Network Pharmacology Study

Author(s): Ping Zhang, Xuanming Liu, Xin Yu, Yuzhen Zhuo, Dihua Li, Lei Yang* and Yanmin Lu*

Volume 27, Issue 11, 2024

Published on: 07 September, 2023

Page: [1566 - 1575] Pages: 10

DOI: 10.2174/1386207326666230717155641

Price: $65

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Abstract

Background: Liriodendrin (LIR) has been reported to improve cardiac function in rats following myocardial infarction. However, its role and mechanism in reparative myocardial fibrosis remain unclear.

Methods: In this study, a rat model of myocardial fibrosis was established via left anterior descending artery ligation and randomly divided into three groups (n = 6 per group): sham-operated, myocardial infarction, and LIR intervention (100 mg/kg/day) groups. The pharmacological effects of LIR were assessed using echocardiography, hematoxylin, and eosin (H&E) staining, and Masson staining. Network pharmacology and bioinformatics were utilized to identify potential mechanisms of LIR, which were further validated via western blot analysis.

Results: Our findings demonstrated that LIR improved cardiac function, histology scores, and col lagen volume fraction. Moreover, LIR downregulated the expression of Beclin-1, LC3-II/LC3-I while upregulating the expression of p62, indicating LIR-inhibited autophagy in the heart after myocardial infarction. Further analysis revealed that the PI3K/Akt signaling pathway was significantly enriched and validated by western blot. This analysis suggested that the ratios of p- PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR were significantly increased.

Conclusion: LIR may attenuate myocardial infarction-induced fibrosis in rats by inhibiting excessive myocardial autophagy, with the potential mechanism involving the activation of the PI3K/Akt/mTOR pathway.

Keywords: Autophagy, liriodendrin, myocardial fibrosis, network pharmacology, PI3K-Akt signaling pathway, myocardial infarction (MI).

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