Schisandrin B ameliorates non-alcoholic liver disease through anti-inflammation activation in diabetic mice.

Type 2 diabetes mellitus (T2DM) is a metabolic risk factor associated with non-alcoholic liver disease (NAFLD). Schisandrin B (Sch B) is a promising agent for NAFLD. However, the actions of Sch B on diabetes-associated NAFLD and the underlying mechanisms are not characterized. This study aimed to assess whether Sch B has beneficial effects on T2DM-associated NAFLD. Sch B (50 mg/kg, gavage) was administrated to C57BL/KSJ db/db mice for 2 weeks. Body weight, liver weight, blood glucose, and insulin resistance were measured. Serum lipid level and liver function were detected using the biochemistry analyzer. Quantitative Real-Time PCR assay was used to evaluate mRNA levers of lipid metabolism genes. Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) staining was performed to measure apoptosis in the liver. Pathological analysis and immunohistochemistry assessment were used to analyze hepatic steatosis and inflammatory infiltration. Sch B supplementation significantly decrease body weight, related liver weight, blood glucose, and serum insulin, and improved insulin resistance in db/db mice. Sch B obviously corrected NAFLD phenotypes including lipid deposition, steatohepatitis, and high levels of hepatic enzymes and serum lipid. In addition, mRNA levels of Sterol response element-bind protein 1c (SREBP-1c), fatty acid synthetase (Fasn), and acetyl-CoA carboxylase (ACC) were markedly downregulated by Sch B treatment. TUNEL-positive cells were also decreased by Sch B. Furthermore, Sch B inhibited the Kupffer cells, IL-1ß, and TNF-α infiltration to the liver. Sch B ameliorated insulin resistance and lipid accumulation under high glucose conditions, which was partly associated with its inhibition of apoptosis and anti-inflammatory actions.

Tetrandrine alleviates cerebral ischemia/reperfusion injury by suppressing NLRP3 inflammasome activation via Sirt-1.

BACKGROUND & AIMS: Tetrandrine (Tet) has been reported to have anti-inflammatory effects and protect from the ischemic strokes. The NLRP3 inflammasome plays a key role in cerebral ischemia/reperfusion (I/R)-induced inflammatory lesions. However, the molecular mechanisms of Tet related to the progression of cerebral ischemia are still unclear. Therefore, the aim of this study was to investigate the possible effects of Tet on cerebral ischemia and the related mechanisms involved in NLRP3 inflammasome. METHODS: C57BL/6J mice used as a cerebral I/R injury model underwent middle cerebral artery occlusion (MCAO) for 2 h following reperfusion for 24 h. Tet (30 mg/kg/day, i.p.) was administered for seven days and 30 min before and after MCAO. Their brain tissues were evaluated for NLRP3 inflammasome and Sirtuin-1 (Sirt-1) expression. An intracerebroventricular injection of Sirt-1 siRNA was administered to assess the activation of the NLRP3 inflammasome. RESULTS: Tet significantly reduced the neurological deficits, infarction volume, and cerebral water content in MCAO mice. Moreover, it inhibited I/R-induced over expression of NLRP3, cleaved caspase-1, interleukin (IL)-1ß, IL-18, and Sirt-1. Sirt-1 knockdown with siRNA greatly blocked the Tet-induced reduction of neurological severity score and infarct volume, and reversed the inhibition of NLRP3 inflammasome activation. CONCLUSION: Our results demonstrate that Tet has benefits for cerebral I/R injury, which are partially related to the suppression of NLRP3 inflammasome activation via upregulating Sirt-1.