Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Imperatorin alleviates post-infarction cardiac fibrosis via the CD44/PI3K/AKT pathway in mice

Articles in Press

Document Type : Original Article

Authors
Hui Yuan 1, 2
YanKun Hao 1
Mohammed Alaa Abdulzahra 3, 4
YueYing Yuan 1
Xuan Li 1
Javeria Qadir 5
ManYu Wang 1
YuanYuan Zhang 1
TingTing Li 1
Jian Sun 6, 1
1 School of Basic Medical Sciences, Mudanjiang Medical University, Mudanjiang 157011, P.R. China
2 School of Stomatology, Mudanjiang Medical University, Mudanjiang 157011, P.R. China
3 DNA Research Center, University of Babylon, Hilla 51001, Iraq
4 Department of Pharmacy, AIAmal College for Specialized Medical Sciences, Karbala -56001, Iraq
5 Department of Biological Sciences, International Islamic University Islamabad, Islamabad 04436, Pakistan
6 Collaborative Innovation Center of Development and Application of North Medicine Resources in Mudanjiang City, Mudanjiang 157011, P.R. China
10.22038/ijbms.2026.95833.20660
Abstract
Objective(s): This study examines the effects of imperatorin (IMP) on cardiac fibrosis in mice with myocardial infarction (MI) and seeks to elucidate the underlying molecular mechanisms.
Materials and Methods: C57BL/6 mice were randomly assigned to a control group, an ISO-induced MI group, and ISO+IMP treatment groups (7.5, 15, and 30 mg/kg). 4D-FastDIA-based quantitative proteomics was used for global proteomic analysis to identify differentially expressed proteins (DEPs) and signaling pathways involved in the anti-fibrotic effects of IMP following MI. Echocardiography was performed to evaluate cardiac function; histopathological analysis and serological indicators were used to assess myocardial injury; and Western blotting was employed to verify the expression and mechanisms of related proteins.
Results: Compared with the ISO group, IMP treatment markedly improved electrocardiographic abnormalities, reduced serum LDH and cTn-I levels, enhanced cardiac function, and attenuated myocardial injury and fibrosis. Proteomic analysis identified 98 DEPs in the ISO/Control group and 127 DEPs in the ISO+IMP/ISO group. GO and KEGG analyses showed that these DEPs were mainly enriched in fibroblast proliferation-related biological processes and ECM-receptor interaction pathways, with significant involvement of the PI3K/AKT signaling pathway. PPI network analysis highlighted FN1, VTN, Colα2(I), Colα1(III), and CD44 as key regulatory proteins, among which CD44 was notably down-regulated by IMP. Molecular docking demonstrated strong binding affinity between IMP and CD44. Western blot results further confirmed that IMP significantly reduced the expression of fibrosis-related proteins and suppressed activation of the CD44/PI3K/AKT signaling pathway.
Conclusion: IMP ameliorates myocardial fibrosis in MI mice by modulating the CD44/PI3K/AKT signaling pathway.
Keywords
CD44
Imperatorin
Myocardial fibrosis
Myocardial infarction
PI3K/AKT
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 22 September 2026