Ginsenoside Rg3 attenuates angiotensin II-induced myocardial hypertrophy through repressing NLRP3 inflammasome and oxidative stress via modulating SIRT1/NF-κB pathway

Background: Ginsenoside Rg3 (Rg3), one of the most potent components extracted from the roots of the traditional Chinese herb Panax ginseng, has prominent roles in anti-tumor and anti-inflammation. However, the applications of Rg3 against myocardial hypertrophy are not fully revealed. Methods: Transverse aortic constriction (TAC) was adopted to build the myocardial hypertrophy model in rats. The in vitro model of myocardial hypertrophy was induced by angiotensin II (Ang II) in the human cardiomyocyte cell line AC16 and HCM, which were then treated with different doses of Rg3. The levels of myocardial hypertrophy markers (ANP, BNP, and beta-MHC) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot (WB) was conducted to verify the expressions of myocardial fibrosis-associated proteins (MyHc, Collagen I, and TGF-beta 1) and oxidative stress (OS) proteins (HO-1 and Nrf2). The markers of fibrosis, hypertrophy, NLRP3 inflammasome and OS in cardiomyocytes were evaluated by qRT-PCR, western blot (WB), enzyme-linked immunosorbent assay (ELISA), and cellular immunofluorescence, respectively. Furthermore, pharmacological intervention on sirtuin-1 (SIRT1) was performed to clarify the function of SIRT1 in Rg3-mediated effects. Results: Rg3 dose-dependently attenuated the Ang II-induced myocardial hypertrophy and fibrosis. What's more, Rg3 markedly inhibited NLRP3-ASC-Caspase1 inflammasome and OS (reflected by SOD, MDA, HO-1, and Nrf2) in cardiomyocytes treated with Ang II. Mechanistically, Rg3 attenuated NF-kappa B activation and promoted SIRT1 expression. Inhibiting SIRT1 (by AGK2) mostly reversed Rg3-mediated effects against Ang II-induced myocardial hypertrophy and fibrosis. In the TAC rat model, administration of Rg3 mitigated myocardial hypertrophy and fibrosis through pressing overproduced inflammation and OS. Conclusion: Rg3 prevents Ang II-induced myocardial hypertrophy via inactivating NLRP3 inflammasome and oxidative stress by modulating the SIRT1/NF-kappa B pathway.