Tanshinone-IIA Mediated Attenuation of Post-Infarction Myocardial Fibrosis via IL-33/ST-2 Signaling Changes in Rat Epicardial Adipose Tissue

Kehan Gao; Xingming Xu; Minyan Sun; Siqi Zhu; Xinyi Luo; Jiahong Li; Kuangyi Liu; Hui Chen; Xiaomin Wang

doi:10.3791/70093

Research Article

Tanshinone-IIA Mediated Attenuation of Post-Infarction Myocardial Fibrosis via IL-33/ST-2 Signaling Changes in Rat Epicardial Adipose Tissue

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DOI:

10.3791/70093

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March 13th, 2026

Kehan Gao^*¹ , Xingming Xu^*¹ , Minyan Sun¹ , Siqi Zhu¹ , Xinyi Luo¹ , Jiahong Li¹ , Kuangyi Liu² , Hui Chen³ , Xiaomin Wang¹

¹Top Discipline of Jiangxi Province, Discipline of Chinese and Western Integrative Medicine, Jiangxi University of Chinese Medicine, ²The Third Affiliated Hospital, Jiangxi Medical College, Nanchang University & Pharmacy Department of Nanchang First Hospital, ³The Third Affiliated Hospital, Jiangxi Medical College, Nanchang University & Cardiovascular Department of Nanchang First Hospital

^* These authors contributed equally

Summary

This study demonstrates that Tanshinone IIA (Tan IIA) mitigates post-myocardial infarction fibrosis, likely via IL-33/ST2 modulation, as shown in animal models and molecular docking, and validated by ELISA and Western blot.

Abstract

Myocardial infarction (MI), a severe form of coronary artery disease, often results in myocardial fibrosis, a key contributor to cardiac dysfunction and heart failure. Epicardial adipose tissue (EAT) is increasingly implicated in cardiovascular pathology through cytokine-mediated modulation of cardiac function. Tanshinone IIA (TanIIA), a lipophilic compound derived from Salvia miltiorrhiza, exhibits anti-inflammatory, antioxidant, and anti-fibrotic properties. This study aimed to evaluate the therapeutic potential of TanIIA in attenuating post-MI myocardial fibrosis and to explore its underlying mechanisms using an integrative approach combining in vivo experiments and in silico analyses. A murine MI model was established, and molecular docking was employed to assess TanIIA binding to key components of the interleukin-33/growth stimulation expressed gene 2 (IL-33/ST2) signaling pathway. Our results showed that TanIIA treatment significantly enhanced cardiac function, reduced histological injury, and mitigated myocardial fibrosis, alongside decreased serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI). TanIIA also attenuated inflammatory responses and oxidative stress in the serum, myocardium, and EAT. Mechanistically, TanIIA downregulated IL-33 and ST2 expression, suppressed the myeloid differentiation factor 88 (MyD88)/nuclear factor kappa-B (NF-κB) pathway, and reduced transforming growth factor-β1 (TGF-β1) levels. In silico analyses further revealed that TanIIA exhibited strong binding affinities for IL-33, ST2, MyD88, and NF-κB p65, with the most stable interaction predicted for ST2. Collectively, these findings indicate that TanIIA alleviates MI-induced myocardial fibrosis by modulating EAT-associated inflammation and oxidative stress, potentially via multi-target inhibition of the IL-33/ST2 axis. These results support TanIIA as a promising therapeutic candidate for the management of post-infarction myocardial fibrosis.

Introduction

Myocardial infarction, pathologically defined as cardiomyocyte death due to prolonged ischemia, remains a life-threatening cardiovascular event¹. Despite significant advances in reperfusion strategies and pharmacotherapy, MI continues to be a leading cause of morbidity and mortality worldwide²^,³^,⁴^,⁵^,⁶. A key pathophysiological consequence of MI is myocardial fibrosis, the excessive deposition of extracellular matrix proteins, which is a major determinant of subsequent adverse clinica....