Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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20(S)-ginsenoside Rg3 exerts anti-fibrotic effect after myocardial infarction by alleviation of fibroblasts proliferation and collagen deposition through TGFBR1 signaling pathways

  • Honglin Xu (Department of Geratology, Affiliated Dongguan Hospital, Southern Medical University (Dongguan People's Hospital)) ;
  • Haifeng Miao (Department of Geratology, Affiliated Dongguan Hospital, Southern Medical University (Dongguan People's Hospital)) ;
  • Guanghong Chen (School of Traditional Chinese Medicine, Southern Medical University) ;
  • Guoyong Zhang (School of Traditional Chinese Medicine, Southern Medical University) ;
  • Yue Hua (School of Traditional Chinese Medicine, Southern Medical University) ;
  • Yuting Wu (School of Traditional Chinese Medicine, Southern Medical University) ;
  • Tong Xu (School of Traditional Chinese Medicine, Southern Medical University) ;
  • Xin Han (School of Traditional Chinese Medicine, Southern Medical University) ;
  • Changlei Hu (School of Traditional Chinese Medicine, Southern Medical University) ;
  • Mingjie Pang (School of Traditional Chinese Medicine, Southern Medical University) ;
  • Leyi Tan (The First School of Clinical Medicine, Southern Medical University) ;
  • Bin Liu (Department of Traditional Chinese Medicine, the Second Affiliated Hospital of Guangzhou Medical University) ;
  • Yingchun Zhou (Department of Geratology, Affiliated Dongguan Hospital, Southern Medical University (Dongguan People's Hospital))
  • Received : 2023.01.17
  • Accepted : 2023.06.24
  • Published : 2023.11.01
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Abstract

Background: Myocardial fibrosis post-myocardial infarction (MI) can induce maladaptive cardiac remodeling as well as heart failure. Although 20(S)-ginsenoside Rg3 (Rg3) has been applied to cardiovascular diseases, its efficacy and specific molecular mechanism in myocardial fibrosis are largely unknown. Herein, we aimed to explore whether TGFBR1 signaling was involved in Rg3's anti-fibrotic effect post-MI. Methods: Left anterior descending (LAD) coronary artery ligation-induced MI mice and TGF-β1-stimulated primary cardiac fibroblasts (CFs) were adopted. Echocardiography, hematoxlin-eosin and Masson staining, Western-blot and immunohistochemistry, CCK8 and Edu were used to study the effects of Rg3 on myocardial fibrosis and TGFBR1 signaling. The combination mechanism of Rg3 and TGFBR1 was explored by surface plasmon resonance imaging (SPRi). Moreover, myocardial Tgfbr1-deficient mice and TGFBR1 adenovirus were adopted to confirm the pharmacological mechanism of Rg3. Results: In vivo experiments, Rg3 ameliorated myocardial fibrosis and hypertrophy and enhanced cardiac function. Rg3-TGFBR1 had the 1.78×10-7 M equilibrium dissociation constant based on SPRi analysis, and Rg3 inhibited the activation of TGFBR1/Smads signaling dose-dependently. Cardiac-specific Tgfbr1 knockdown abolished Rg3's protection against myocardial fibrosis post-MI. In addition, Rg3 downregulated the TGF-β1-mediated CFs growth together with collagen production in vitro through TGFBR1 signaling. Moreover, TGFBR1 adenovirus partially blocked the inhibitory effect of Rg3. Conclusion: Rg3 improves myocardial fibrosis and cardiac function through suppressing CFs proliferation along with collagen deposition by inactivation of TGFBR1 pathway.

Keywords

Acknowledgement

This study was supported by the National Natural Science Foundation of China (grant numbers 82274417, 81973645, 81774100), Natural Science Foundation of Guangdong Province (Nos. 2022A1515011630, 2021A1515220010), and Guangdong Basic and Applied Basic Research Foundation (No. 2022A1515110870).

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