Ginsenoside Rb3 upregulates sarcoplasmic reticulum Ca2+-ATPase expression and improves the contractility of cardiomyocytes by inhibiting the NF-?B pathway

A causal relationship between ginsenoside Rb3 (G-Rb3) and improved inflammation and cardiac function has not been established. To determine which specific signaling pathways were involved in G-Rb3 improvement of inflammation and myocardial function. In vivo, we found that G-Rb3 decreased the levels of both nuclear factor kappa B (NF-KB p65) and CD45, an inflammatory marker. G-Rb3 also enhanced key proteins of the contraction unit (cardiac troponin protein I (cTnI) and a-actinin) to improve cardiac function. G-Rb3 inhibited NF-KB p65 nuclear translocation in vitro, as verified by western blot and IF. When NF-KB p65 was overexpressed, a decrease in cyclic nucleotide phosphodiesterase 3B (PDE3B) and SERCA2a expression, while no statistical significance was observed in the expressions of cAMP, PKA, and calcium/calmodulin-dependent protein kinase type II (CaMKII) in each group. The NF-KB p65 plasmid blocked the SERCA2a promoter, as verified by the luciferase reporter system, and G-Rb3 truncated the NF-KB p65 block on the SERCA2a promoter. qPCR was also used to confirm that G-Rb3 increased the mRNA of SERCA2a. In conclusion, we confirmed that the mechanisms of G-Rb3 on ventricular systolic dysfunction causing inflammation are not via the cAMP/PKA pathway, but via suppressing the blockage of NF-KB p65 on the SERCA2a promoter and increasing the SERCA2a expression.

Automated summary

This study found that G-Rb3 improves cardiac function and reduces inflammation by inhibiting the nuclear translocation of NF-KB p65, reducing the levels of the inflammatory marker CD45, and enhancing the expression of key proteins in the contraction unit. Further experiments confirmed that G-Rb3 improves cardiac function by suppressing the blockage of NF-KB p65 on the SERCA2a promoter and increasing SERCA2a expression.