Ginsenoside Rg1 attenuates cardiomyocyte apoptosis and inflammation via the TLR4/NF-kB/NLRP3 pathway.

Abstract

Sepsis-induced myocardial dysfunction (SIMD) causes high mortality in seriously ill patients. Ginsenoside Rg1 has been proven to have effective anti-inflammatory and antiapoptotic properties. However, the specific role of Rg1 in SIMD and the molecular mechanism remain unclear. Hence, we aimed to investigate the latent effects of ginsenoside Rg1 against SIMDand explore its underlying mechanisms. Male C57BL/6J mice and neonatal rat cardiomyocytes (NRCMs) were used as in vivo and in vitro models, respectively. Western blot analysis was used to detect the level of protein expression, and reverse transcription polymerase chain reactionwas conducted to determine the messenger RNAexpression of inflammatory factors. The terminal deoxynucleotidyl transferase-mediated nick end labelingassay and flow cytometry were used to determine the apoptosis rate. Echocardiography was performed to assess cardiac function. The results showed that Rg1 improved cardiac function and attenuated lipopolysaccharide (LPS)-induced apoptosis and inflammation in mice. In addition, in NRCMs, Rg1 downregulated the expression of LPS-induced inflammatory cytokines and reversed the increased expression of Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), and NOD-like receptor 3 (NLRP3). In addition, treatment with TLR4 small interfering RNA (siRNA), a p-NF-κB inhibitor, or NLRP3 siRNA suppressed LPS-induced apoptosis and inflammation. In conclusion, Rg1 can attenuate LPS-induced inflammation and apoptosis both in NRCMs and septic mice and restore impaired cardiac function. Moreover, Rg1 may exert its effect via blocking the TLR4/NF-κB/NLRP3 pathway.