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ReferenceID 4784

Calycosin reduces myocardial fibrosis and improves cardiac function in post-myocardial infarction mice by suppressing TGFBR1 signaling pathways

Phytomedicine

Background: Excessive myocardial fibrosis is the pathological basis of heart failure following myocardial infarction (MI). Although calycosin improves cardiac function, its effect on cardiac fibrosis and cardiac function

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Reference Id
4784
Evidence Id
21374
Core Evidence Id
21374
Source Reference Id
2808
Herb2 Reference Id
HBREF003605
Subject Paper Key
HBIN019425_35752078
Pubmed Id
35752078
Doi
10.1016/j.phymed.2022.154277
Paper Title
Calycosin reduces myocardial fibrosis and improves cardiac function in post-myocardial infarction mice by suppressing TGFBR1 signaling pathways
Paper Abstract
Background: Excessive myocardial fibrosis is the pathological basis of heart failure following myocardial infarction (MI). Although calycosin improves cardiac function, its effect on cardiac fibrosis and cardiac function after MI in mice and its precise mechanism remain unclear. Purpose: Here, we firstly investigated the effects of calycosin on cardiac fibrosis and ventricular function in mice after MI and the role of transforming growth factor-beta receptor 1 (TGFBR1) signaling in the amelioration of cardiac fibrosis and ventricular function. Methods: In vivo effects of calycosin on cardiac structure and function in mice with MI induced by left anterior descending coronary artery ligation were determined by hematoxylin and eosin staining, Masson trichrome staining, and echocardiography. The molecular mechanism of the interaction between TGFBR1 and calycosin was investigated using molecular docking, molecular dynamics (MD) simulation, surface plasmon resonance imaging (SPRi), immunohistochemistry, and western blotting (WB). Subsequently, cardiac-specific Tgfbr1 knockout mice were used to verify the effects of calycosin. The effect of calycosin on primary cardiac fibroblasts (CFs) proliferation and collagen deposition was detected using cell counting (CCK-8), EdU assay, and WB in vitro. CFs infected with an adenovirus that encodes TGFBR1 were used to verify the effects of calycosin. Results: In vivo, calycosin attenuated myocardial fibrosis and cardiac dysfunction following MI in a dose-dependent pattern. Calycosin-TGFBR1 complex was found to have a binding energy of -9.04 kcal/mol based on molecular docking. In addition, calycosin bound steadily in the cavity of TGFBR1 during the MD simulation. Based on SPRi results, the solution equilibrium dissociation constant for calycosin and TGFBR1 was 5.11 × 10 -5 M. Calycosin inhibited the expression of TGFBR1, Smad2/3, collagen I, and collagen III. The deletion of TGFBR1 partially counteracted these effects. In vitro, calycosin suppressed CFs proliferation and collagen deposition after TGF-β1 stimulation by suppressing the TGFBR1 signaling pathway. The suppressive effects of calycosin were partially rescued by overexpression of TGFBR1. Conclusion: Calycosin attenuates myocardial fibrosis and cardiac dysfunction following MI in mice in vivo via suppressing the TGFBR1 signaling pathway. Calycosin suppresses CFs proliferation and collagen deposition induced by TGF-β1 via inhibition of the TGFBR1 signaling pathway in vitro.
Journal
Phytomedicine
Publish Year
2022
Experiment Subject
mouse
Experiment Type
Animal Experiment
Phenotype Related
Myocardial Fibrosis; Cardiac Dysfunction; Heart Failure; Myocardial Infarction; Excessive Myocardial Fibrosis; Cardiac Fibrosis
Paper Title Cn
Paper Title En
Calycosin reduces myocardial fibrosis and improves cardiac function in post-myocardial infarction mice by suppressing TGFBR1 signaling pathways
Bilingual Status
semi_complete