Title: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
Volume: 30
Issue: 1
Author(s): Guanghao Niu, Ying Zhao, Huafeng Song, Quan Song, Xiaoyun Yin, Zengyan Zhu*Junchi Xu*
Affiliation:
- Department of Pharmacy, The Affiliated Children’s Hospital of Soochow University, Suzhou, China
- Department of Pharmacy, The Affiliated Infectious Diseases Hospital of Soochow University, The Fifth People’s Hospital of
Suzhou, Suzhou, China
Keywords:
Myocardial fibrosis, marein, cardiac fibroblasts, TGF-β1, HIF-1α, Smad2/3.
Abstract:
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.
