Gypenosides ameliorate high-fat diet-induced non-alcoholic steatohepatitis via farnesoid X receptor activation

Abstract

BackgroundGypenosides (Gyps), the major botanical component of Gynostemma pentaphyllum, was found to up-regulate the farnesoid X receptor (FXR) in a mouse model of non-alcoholic steatohepatitis (NASH). However, the exact role of FXR and underlying mechanisms in Gyps-mediated effects on NASH remain to be elucidated.PurposeThis study investigated whether Gyps attenuates NASH through directly activating FXR in high-fat diet (HFD)-induced NASH, and delineated the molecular pathways involved.Study designA mouse model of HFD-induced NSAH was used to examine effects of Gyps on NASH with obeticholic acid (OCA) as a positive control, and the role of FXR in its mechanism of action was investigated in wild-type (WT) and FXR knockout (KO) mice.MethodsWT or FXR KO mice were randomly assigned into four groups: normal diet (ND) group as negative control, HFD group, HFD + Gyps group, or HFD + OCA group.ResultsTreatment with Gyps and OCA significantly improved liver histopathological abnormalities in HFD-induced NASH, reduced the non-alcoholic fatty liver disease (NAFLD) activity score (NAS), and lowered hepatic triglyceride (TG) content compared with the HFD group. In agreement with these liver tissue changes, biochemical tests of blood samples revealed that alanine aminotransferase (ALT), aspartate aminotransferase (AST), TG, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), and fasting insulin (FINS) levels were significantly lower in the HFD + Gyps vs. HFD group. Furthermore, Gyps and OCA treatment significantly up-regulated hepatic FXR, small heterodimer partner (SHP), carnitine palmitoyltransferase 1A (CPT1A), and lipoprotein lipase (LPL) expression, and significantly down-regulated sterol-regulatory element binding protein 1 (SREBP1), fatty acid synthetase (FASN), and stearoyl-CoA desaturase 1 (SCD1) protein levels compared with the HFD group in WT mice but not in FXR KO mice. Notably, Gyps- and OCA-mediated pharmacological effects were significantly abrogated by depletion of the FXR gene in FXR KO mice.ConclusionGyps ameliorated HFD-induced NASH through the direct activation of FXR and FXR-dependent signaling pathways.

LanGui tea, an herbal medicine formula, protects against binge alcohol-induced acute liver injury by activating AMPK-NLRP3 signaling

“…These components possess potential applications in medicine and food due to their diverse pharmacological activities including anti-inflammatory, antioxidation, antifibrosis, antiobesity, hepatoprotective, and lipid-lowering effects [ 27 – 29 ]. Notably, G. pentaphyllum and gypenosides have shown promise in alleviating hepatic steatosis, mitochondrial impairment, and inflammatory response, ultimately improving liver dysfunction, particularly in cases of fatty liver [ 28 , 40 ]. Furthermore, cinnamon has demonstrated therapeutic benefits by reducing hyperlipidemia, liver enzymes, insulin resistance, and hepatic steatosis in both NAFLD patients and animal models [ 27 , 41 ].…”

Effects of kiwi fruit (Actinidia chinensis) polysaccharides on metabolites and gut microbiota of acrylamide-induced mice

“…AST and ALT are widely distributed in various tissues, especially in the liver. Increased AST levels can be used as an indicator of mitochondrial damage, while high ALT levels suggest membrane damage ( 29 ). When the liver function or structure is damaged, these transaminases are released from the liver increasing their serum levels.…”

New natural protein tyrosine phosphatase 1B inhibitors from Gynostemma pentaphyllum

“… 4 , 5 It has also been prescribed as traditional Chinese medicine to treat various diseases, such as non-alcoholic steatohepatitis (NASH) and diabetes. 6 Previous phytochemical investigations showed that the dammarane triterpenoid saponins, sterols and flavonoids were the major chemical constituents in G. pentaphyllum . 7 , 8 To date, more than 180 dammarane triterpenoid saponins were reported from G. pentaphyllum with various bioactivities including antioxidant, antidiabetic, anti-inflammatory, hepatoprotective and antitumor effects.…”