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Marein Ameliorates Myocardial Fibrosis by Inhibiting HIF-1α and TGF-β1/Smad2/3 Signaling Pathway in Isoproterenol-stimulated Mice and TGF-β1-stimulated Cardiac Fibroblasts

[ Vol. 30 , Issue. 1 ]


Guanghao Niu, Ying Zhao, Huafeng Song, Quan Song, Xiaoyun Yin, Zengyan Zhu* and Junchi Xu*   Pages 71 - 80 ( 10 )


Background: Myocardial fibrosis significantly contributes to the pathogenesis and progression of heart failure.

Objective: We probe into the impact of marein, a key bioactive compound in functional food Coreopsis tinctoria, on isoproterenol-stimulated myocardial fibrotic mice and transforming growth factor β1 (TGF-β1)-stimulated cardiac fibroblasts (CFs).

Methods: Isoproterenol was administered to the experimental mice via subcutaneous injection, and simultaneous administration of marein (25-100 mg/kg) was performed via oral gavage. CFs were stimulated with TGF- β1 to trigger differentiation and collagen synthesis, followed by treatment with marein at concentrations of 5-20 μM.

Results: Treatment with marein in mice and CFs resulted in a significant reduction in the protein expression levels of α-smooth muscle actin, collagen type I, and collagen type III. Additionally, marein treatment decreased the protein expression levels of TGF-β1, hypoxia-inducible factor-1α (HIF-1α), p-Smad2/3, and Smad2/3. Notably, molecular docking analysis revealed that marein directly targets HIF-1α.

Conclusion: Marein might exert a protective function in isoproterenol-stimulated myocardial fibrotic mice and TGF-β1-stimulated CFs, which might result from the reduction of TGF-β1 induced HIF-1α expression, then inhibiting p-Smad2/3 and Smad2/3 expressions.


Myocardial fibrosis, marein, cardiac fibroblasts, TGF-β1, HIF-1α, Smad2/3.


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