Panax ginseng exerts cardioprotective effect post myocardial infarction by attenuating myocardial fibrosis and inflammation through SIRT1 signaling pathways

Abstract

Background

Myocardial fibrosis and inflammation induce adverse cardiac remodeling post-myocardial infarction (MI). Panax ginseng (P. ginseng) is beneficial for diverse cardiovascular diseases. However, the therapeutic effect and molecular mechanism underlying cardiac remodeling are largely unclear.

Methods

A MI mouse model was constructed through permanent left anterior descending (LAD) coronary artery ligation. Transforming growth factor-β1 (TGF-β1) or lipopolysaccharide (LPS) was used for stimulating cardiac fibroblasts (CFs) or RAW264.7 macrophages to construct the collagen synthesis and inflammation model in vitro. The cardiac structure and function were detected through hematoxylin-eosin staining, Masson staining, and echocardiography, while myocardial fibrosis and inflammation markers were determined by Western-blot, immunohistochemistry, RT-PCR, and ELISA. Additionally, the Silent information regulator 1 (SIRT1)/nuclear factor-κB (NF-κB) mediated NOD like receptor 3 (NLRP3) inflammasome and TGF-β receptor I (TGFBR1) signaling pathways were also evaluated. A SIRT1 selective inhibitor (EX-527) was used for confirming the pharmacological mechanism of P. ginseng.

Results

In vivo, P. ginseng alleviated ventricular remodeling, enhanced heart function, and ameliorated collagen I, collagen III, IL-1β, and IL-18 levels dose-dependently. Moreover, P. ginseng significantly suppressed NLRP3-caspase1 inflammasome and TGFBR1/Smads signaling in MI mice. In vitro, P. ginseng significantly suppressed collagen and inflammation markers, NLRP3 inflammasome and TGFBR1/Smads signaling in TGF-β1-induced CFs or LPS-stimulated RAW264.7 cells. Mechanistically, P. ginseng suppressed NF-κB activity while promoting SIRT1 expression. SIRT1 suppression by EX-527 partially abolished the protective effects of P. ginseng in TGF-β1-induced CFs.

Conclusion

P. ginseng protects from adverse cardiac remodeling by attenuating myocardial fibrosis and inflammation post-MI through the regulation of SIRT1 and its downstream signaling pathways.