Schisandra chinensis extract ameliorates nonalcoholic fatty liver via inhibition of endoplasmic reticulum stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis (Turcz.) Baill. (SC) is a traditional Chinese herbal medicine with diverse pharmacological activities for treatment of various human diseases. Endoplasmic reticulum (ER) stress is associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effects of methanol extract of Schisandra chinensis (SC extract) against ER stress-induced NAFLD in vitro and in vivo. MATERIAL AND METHODS: The protective effects of SC extract were examined in tunicamycin- or palmitate-treated HepG2 cells in vitro, and in tunicamycin-injected mice or high fed diet (HFD) obese mice in vivo. Expression of ER stress markers including glucose regulated protein 78 (GRP78), C/EBP homolog protein (CHOP), and X-box-binding protein-1 (XBP-1), and triglyceride accumulation were measured in HepG2 cells and in the liver of mice. RESULTS: SC extract significantly inhibited expression of tunicamycin-induced ER stress markers in tunicamycin-treated HepG2 cells and in the liver of tunicamycin-injected mice, and it also inhibited tunicamycin-induced triglyceride accumulation. Similar observations were made under physiological ER stress conditions such as in palmitate-treated HepG2 cells and in the liver of HFD obese mice. In addition, SC extract repressed the expression of inflammatory genes and lipogenic genes in palmitate-treated HepG2 cells. Schisandrin, an abundant bioactive lignan in SC extract, inhibited the expression of ER stress markers in tunicamycin-or palmitate-treated HepG2 cells, whereas Gomisin J did not affect ER stress markers. CONCLUSIONS: SC attenuates ER stress and prevents development of NAFLD. SC may be useful as a pharmacological agent for protection against ER stress-induced human diseases.

Protective Effects of Alisma orientale Extract against Hepatic Steatosis via Inhibition of Endoplasmic Reticulum Stress.

Endoplasmic reticulum (ER) stress is associated with the pathogenesis of hepatic steatosis. Alisma orientale Juzepzuk is a traditional medicinal herb for diuretics, diabetes, hepatitis, and inflammation. In this study, we investigated the protective effects of methanol extract of the tuber of Alisma orientale (MEAO) against ER stress-induced hepatic steatosis in vitro and in vivo. MEAO inhibited the tunicamycin-induced increase in luciferase activity of ER stress-reporter constructs containing ER stress response element and ATF6 response element. MEAO significantly inhibited tunicamycin-induced ER stress marker expression including GRP78, CHOP, and XBP-1 in tunicamycin-treated Human hepatocellular carcinoma (HepG2) cells and the livers of tunicamycin-injected mice. It also inhibited tunicamycin-induced accumulation of cellular triglyceride. Similar observations were made under physiological ER stress conditions such as in palmitate (PA)-treated HepG2 cells and the livers of high-fat diet (HFD)-induced obese mice. MEAO repressed hepatic lipogenic gene expression in PA-treated HepG2 cells and the livers of HFD obese mice. Furthermore, MEAO repressed very low-density lipoprotein receptor (VLDLR) expression and improved ApoB secretion in the livers of tunicamycin-injected mice or HFD obese mice as well as in tunicamycin or PA-treated HepG2 cells. Alismol, a guaiane-type sesquiterpenes in Alisma orientale, inhibited GRP78 expression in tunicamycin-treated HepG2 cells. In conclusion, MEAO attenuates ER stress and prevents hepatic steatosis pathogenesis via inhibition of expression of the hepatic lipogenic genes and VLDLR, and enhancement of ApoB secretion.

Vigna nakashimae extract prevents hepatic steatosis in obese mice fed high-fat diets.

Vigna species are important food resources and are traditionally used for the treatment of various diseases. In this study, we examined the inhibitory effects of Vigna nakashimae (VN) extract on high-fat diet (HFD)-induced hepatic steatosis and elucidated the molecular mechanisms. C57BL/6J mice were fed an HFD with or without VN extract for 16 weeks. VN extract decreased HFD-induced body weight, liver weight, hepatic lipid accumulation, and plasma alanine aminotransferase, and suppressed oxidative stress and inflammation associated with hepatitis. VN extract decreased plasma lipid levels and the expression of lipogenic genes in the livers of HFD-fed mice. VN extract significantly increased phosphorylation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and expression of fatty acid oxidation genes in the liver of VN-treated HFD mice and HepG2 cells. Further, VN extract inhibited insulin or glucose-stimulated lipogenesis in HepG2 cells. In conclusion, VN extract prevents HFD-induced hepatic steatosis and lipotoxicity through AMPK activation.

Antiobesity activity of Vigna nakashimae extract in high-fat diet-induced obesity.

In this study, we evaluated the antiobesity effects of Vigna nakashimae (VN) extract and elucidated the underlying mechanisms. VN extract suppressed adipocyte differentiation and significantly attenuated the expression of adipogenic genes in 3T3-L1 cells. It decreased the expression of peroxisome proliferator-activated receptor γ (PPARγ) and its target genes in fully differentiated 3T3-L1 cells. Moreover, it enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl CoA carboxylase (ACC), and increased the expression of fatty acid oxidation genes. In high-fat diet (HFD) fed mice, VN extract suppressed HFD-induced increases in body weight, epididymal fat tissue weight, and hepatic lipid levels, and decreased the plasma levels of triacylglycerols, fatty acid, total cholesterol, and inflammatory cytokines. Consistently with in vitro study results, VN extract prevented HFD-induced increases in the expression of PPARγ and its target genes, and restored the decrease in the phosphorylation of AMPK and ACC in epididymal fat and liver tissues. These findings suggest that Vigna nakashimae prevents obesity through suppression of PPARγ expression and activation of AMPK, and that it might be a useful dietary supplement for the prevention of obesity.