Combinatorial Chemistry & High Throughput ScreeningCombinatorial Chemistry & High Throughput ScreeningCombinatorial Chemistry & High Throughput Screening1386-20731875-5402Bentham Science64387210.2174/1386207326666230717155641ChemistryResearch ArticleProtective Effects of Liriodendrin on Myocardial Infarction-Induced Fibrosis in Rats via the PI3K/Akt Autophagy Pathway: A Network Pharmacology StudyZhangPinginfo@benthamscience.netLiuXuanminginfo@benthamscience.netYuXininfo@benthamscience.netZhuoYuzheninfo@benthamscience.netLiDihuainfo@benthamscience.netYangLeiinfo@benthamscience.netLuYanmininfo@benthamscience.netDepartment of Cardiology, Tianjin Nankai HospitalGraduate School, Tianjin University of Traditional Chinese MedicineTianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai HospitalTianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital0106202427111566157507012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://rjpbr.com/1386-2073/article/view/643872

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.

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