Ginsenoside Rb1 Mitigates Myocardial Fibrosis Through Inhibiting Exosomal‐Derived miRNA‐21–Associated Inflammation and Cardiac Signaling

Myocardial fibrosis exemplifies a crucial pathological event in the escalation of heart failure. Natural bioactive agents that can modulate and mitigate myocardial fibrosis hold promising potential as key therapeutic and preventive strategies for managing heart failure. In this study, Ginsenoside Rb1 was found to attenuate myocardial fibrosis and suppress inflammatory responses by downregulating exosomal miRNA-24 expression in the experimental mice models. Primary mouse cardiac fibroblasts (pMCFs) were isolated from neonatal C57BL/6J mice for in vitro assays. For the in vivo investigations, adult C57BL/6J mice were utilized to assess the effects of Rb1 and Ang II on exosome-derived inflammatory pathways. Multiple analytical techniques, including qPCR, Western blotting, nanoparticle tracking analysis (NTA), BrdU staining, and ELISA, were employed to evaluate gene expression, protein levels, exosome characterization, cell proliferation, and cytokine secretion. The obtained results showed that Rb1 prevents Ang II-induced cell death and BrdU-positive cells in the pMCFs. Moreover, we have confirmed that the exosomes derived from pMCF cells have a size range of 80-250 nm, with a peak at 149 nm. RBb-1 prevented the Ang II-exposure-stimulated exosomal mRNA and protein expression of cardiac fibrosis markers (COL1a1, COL3a1, ACTA2, and TGFβ1) in both pMCFs and mice models. Moreover, Rb1 inhibited the inflammatory expression which was confirmed by ELISA. In addition to that, Rb1 impedes the exosomal mRNA expression of miRNA-21 in the mouse model. This study will open up a new insight into the relationship between Rb1 and miRNA-21, which mitigates myocardial fibrosis in the Ang II-induced mouse model.