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.

The present study aimed to investigate the effects of sericin on the p38MAPK signaling pathway and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in the kidney of rats with type 2 diabetes mellitus (T2DM). A total of 36 male Sprague-Dawley rats were randomly divided into the normal group, T2DM model group and sericin group (n=12 rats/group). A T2DM model was developed through intraperitoneal injection of streptozotocin (35 mg·kg-1·d-1 for 2 consecutive days), and a high-fat and high-sugar diet. The T2DM rats in the sericin group were administered 2.4 g·kg-1·d-1 sericin for 35 days, and rats in the other groups were administered an equal volume of normal saline for 35 days. Fasting blood glucose was measured using the glucose oxidase method. Kidney tissue morphology was observed by H&E staining. Immunohistochemistry, western blotting, ELISA and reverse transcription-quantitative PCR were used to detect the levels of MKK6, p38MAPK, phosphorylated (p)-p38MAPK, NF-κB, IL-1β, IL-6, NLRP3 and caspase-1 in rat kidney tissues. The results revealed that blood glucose concentration, and the expression levels of MKK6, p-p38MAPK, NF-κB, IL-1β, IL-6, NLRP3 and caspase-1 were significantly increased in the T2DM group compared with those in the normal group (P<0.05). In addition, obvious pathological changes were observed in the T2DM group. Conversely, glucose concentration, and the expression levels of MKK6, p-p38MAPK, NF-κB, IL-1β, IL-6, NLRP3 and caspase-1 were significantly reduced in the sericin group compared with those in the T2DM group (P<0.05). The pathological changes were also obviously reduced. Notably, there was no significant difference in p38MAPK expression among the three groups (P>0.05). Collectively, the present study revealed that sericin may downregulate the expression levels of MKK6, p-p38MAPK, NF-κB, IL-1β, IL-6, NLRP3 and caspase-1, and inhibit activation of renal p38MAPK signaling and NLRP3-associated inflammation, which in turn may protect against kidney damage caused by T2DM.