dehydroeburicoic-acid and Disease-Models--Animal

This study investigated the potential effects of dehydroeburicoic acid (TT), a triterpenoid compound from Antrodia camphorata, in vitro and examined the effects and mechanisms of TT on glucose and lipid homeostasis in high-fat-diet (HFD)-fed mice. The in vitro study examined the effects of a MeOH crude extract (CruE) of A. camphorata and Antcin K (AnK; the main constituent of fruiting body of this mushroom) on membrane glucose transporter 4 (GLUT4) and phospho-Akt in C2C12 myoblasts cells. The in vitro study demonstrated that treatment with CruE, AnK and TT increased the membrane levels of glucose transporter 4 (GLUT4) and phospho-Akt at different concentrations. The animal experiments were performed for 12 weeks. Diabetic mice were randomly divided into six groups after 8 weeks of HFD-induction and treated with daily oral gavage doses of TT (at three dose levels), fenofibrate (Feno) (at 0.25 g/kg body weight), metformin (Metf) (at 0.3 g/kg body weight) or vehicle for another 4 weeks while on an HFD diet. HFD-fed mice exhibited increased blood glucose levels. TT treatment dramatically lowered blood glucose levels by 34.2%~43.4%, which was comparable to the antidiabetic agent-Metf (36.5%). TT-treated mice reduced the HFD-induced hyperglycemia, hypertriglyceridemia, hyperinsulinemia, hyperleptinemia, and hypercholesterolemia. Membrane levels of GLUT4 were significantly higher in CruE-treated groups in vitro. Skeletal muscle membrane levels of GLUT4 were significantly higher in TT-treated mice. These groups of mice also displayed lower mRNA levels of glucose-6-phosphatase (G6 Pase), an inhibitor of hepatic glucose production. The combination of these agents produced a net hypoglycemic effect in TT-treated mice. TT treatment enhanced the expressions of hepatic and skeletal muscle AMP-activated protein kinase (AMPK) phosphorylation in mice. TT-treated mice exhibited enhanced expression of hepatic fatty acid oxidation enzymes, including peroxisome proliferator-activated receptor α (PPARα) and increased mRNA levels of carnitine palmitoyl transferase Ia (CPT-1a). These mice also exhibited decreased expression levels of lipogenic fatty acid synthase (FAS) in liver and adipose tissue and reduced mRNA levels of hepatic adipocyte fatty acid binding protein 2 (aP2) and glycerol-3-phosphate acyltransferase (GPAT). These alterations resulted in a reduction in fat stores within the liver and lower triglyceride levels in blood. Our results demonstrate that TT is an excell

Topics: AMP-Activated Protein Kinases; Animals; Antrodia; Biomarkers; Diabetes Mellitus, Experimental; Diet, High-Fat; Disease Models, Animal; Dyslipidemias; Energy Metabolism; Gene Expression; Gene Expression Profiling; Glucose Transporter Type 4; Hypoglycemic Agents; Lanosterol; Liver; Mice; Organ Specificity; Phosphorylation; PPAR alpha; Proto-Oncogene Proteins c-akt

The hepatoprotective effects of eburicoic acid (TR1) and dehydroeburicoic acid (TR2) from Antrodia camphorata (AC) against carbon tetrachloride (CCl4)-induced liver damage were investigated in mice. TR1 and TR2 was administered intraperitoneally (i.p.) for 7 days prior to the administration of CCl4. Pretreatment with TR1 and TR2 prevented the elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and liver lipid peroxides in CCl4-treated mice. The activities of antioxidant enzymes [catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)], nitric oxide (NO) production, and tumour necrosis factor-alpha (TNF-α) were decreased after the treatment with TR1 and TR2 in CCl4-treated mice. Western blotting revealed that TR1 and TR2 significantly decreased inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions and increased the expression of cytochrome P4502E1 (CYP2E1) in CCl4-treated mice. Therefore, we speculate that TR1 and TR2 protect the liver from CCl4-induced hepatic damage via antioxidant and anti-inflammatory mechanisms.

Topics: Acute Disease; Alanine Transaminase; Animals; Antrodia; Aspartate Aminotransferases; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Glutathione Peroxidase; Humans; Lanosterol; Liver; Male; Mice; Mice, Inbred ICR; Nitric Oxide; Oxidative Stress; Superoxide Dismutase