Protective effect of acidic polysaccharide from Schisandra chinensis on acute ethanol-induced liver injury through reducing CYP2E1-dependent oxidative stress.

AIM: Schisandra chinensis is a well-known traditional Chinese medicine used mainly as a recipe for hepatoprotection. Modern researches have revealed that the hepatoprotection is related to its lignans and crude polysaccharide. In this study, we examined the effect and mechanism of Schisandra chinensis acidic polysaccharide (SCAP) on the liver injury induced by ethanol. MAIN METHODS: SCAP was extracted with water extraction and ethanol precipitation. Liver injury models of both mice and HepG2 cells were produced by ethanol. The liver index, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum of the mice and cell culture supernatant were examined; HE staining was performed for observing pathological changes of liver. The malondialdehyde (MDA) level and superoxide dismutase (SOD) activities in serum, liver tissue and HepG2 cells, and triglyceride (TG) content in liver tissue were tested. Western blot was conducted to determine cytochrome P450 2E1 (CYP2E1) expression in liver tissue of mice and HepG2 cells. KEY FINDINGS: SCAP significantly reduced serial AST and ALT levels in the injuried liver and HepG2 cells induced by ethanol and also decreased TG level in the liver tissue. SCAP also obviously improved the hepatopathological changes and decreased MDA level as well as increased SOD activities in the serum, liver tissue and HepG2 cells induced by ethanol. Furthermore, Western blot analysis indicated that SCAP significantly inhibited the upregulation of CYP2E1 protein. SIGNIFICANCE: SCAP has a protective effect on ethanol-induced liver injury in mice and cells, and the mechanism underlying may be via inhibiting the expression of CYP2E1 protein and then alleviating oxidative stress injury induced by ethanol.

Schisandra polysaccharide inhibits hepatic lipid accumulation by downregulating expression of SREBPs in NAFLD mice.

BACKGROUND: Hepatoprotective effects of Chinese herbal medicine Schisandra Chinensis (Schisandra) have been widely investigated. However, most studies were focused on its lignan extracts. We investigated the effects of Schisandra polysaccharide (SCP) in a mouse model of non-alcoholic fatty liver disease (NAFLD), and studied its effect on sterol regulatory element binding proteins (SREBPs) and the related genes. METHODS: The mouse model of NAFLD was established by feeding mice with a high-fat diet for 16 weeks. Effect of SCP-treatment (100 mg/kg, once daily for 12 weeks) on biochemical parameters and liver histopathology was assessed. Relative levels of sterol regulatory element-binding proteins (SREBPs) and their gene expressions were determined by quantitative real-time polymerase chain reaction and Western Blot. RESULTS: SCP significantly reduced the liver index by 12.0%. Serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol, alanine aminotransferase and aspartate aminotransferase were decreased by 31.3, 28.3, 42.8, 20.1 and 15.5%, respectively. Serum high-density lipoprotein cholesterol was increased by 26.9%. Further, SCP lowered hepatic TC and TG content by 27.0% and 28.3%, respectively, and alleviated fatty degeneration and necrosis of liver cells. A significant downregulation of mRNA and protein expressions of hepatic lipogenesis genes, SREBP-1c, fatty acid synthase and acetyl-CoA carboxylase, and the mRNA expression of liver X receptor α (LXRα) was observed in NAFLD mice treated with SCP. SCP also significantly reduced the hepatic expression of SREBP-2 and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). CONCLUSION: These findings demonstrate the hepatoprotective effects of SCP in a mouse model of NAFLD; the effects may be mediated via downregulation of LXRα/SREBP-1c/FAS/ACC and SREBP-2/HMGCR signaling pathways in the liver.