scholarly journals Antcin K, a Triterpenoid Compound fromAntrodia camphorata, Displays Antidiabetic and Antihyperlipidemic Effects via Glucose Transporter 4 and AMP-Activated Protein Kinase Phosphorylation in Muscles

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Yueh-Hsiung Kuo ◽  
Cheng-Hsiu Lin ◽  
Chun-Ching Shih ◽  
Chang-Syun Yang

The purpose of this study was to screen firstly the potential effects of antcin K (AnK), the main constituent of the fruiting body ofAntrodia camphorata,in vitroand further evaluate the activities and mechanisms in high-fat-diet- (HFD-) induced mice. Following 8-week HFD-induction, mice were treated with AnK, fenofibrate (Feno), metformin (Metf), or vehicle for 4 weeks afterward. In C2C12 myotube cells, the membrane GLUT4 and phospho-Akt expressions were higher in insulin and AnK-treated groups than in the control group. It was observed that AnK-treated mice significantly lowered blood glucose, triglyceride, total cholesterol, and leptin levels in AnK-treated groups. Of interest, AnK at 40 mg/kg/day dosage displayed both antihyperglycemic effect comparable to Metf (300 mg/kg/day) and antihypertriglyceridemic effect comparable to Feno (250 mg/kg/day). The combination of significantly increased skeletal muscular membrane expression levels of glucose transporter 4 (GLUT4) but decreased hepatic glucose-6-phosphatase (G6 Pase) mRNA levels by AnK thus contributed to a decrease in blood glucose levels. Furthermore, AnK enhanced phosphorylation of AMP-activated protein kinase (phospho-AMPK) expressions in the muscle and liver. Moreover, AnK treatment exhibited inhibition of hepatic fatty acid synthase (FAS) but enhancement of fatty acid oxidation peroxisome proliferator-activated receptorα(PPARα) expression coincident with reduced sterol response element binding protein-1c (SREBP-1c) mRNA levels in the liver may contribute to decreased plasma triglycerides, hepatic steatosis, and total cholesterol levels. The present findings indicate that AnK displays an advantageous therapeutic potential for the management of type 2 diabetes and hyperlipidemia.

2019 ◽  
Vol 20 (19) ◽  
pp. 4897 ◽  
Author(s):  
Cheng-Hsiu Lin ◽  
Li-Wei Hsiao ◽  
Yueh-Hsiung Kuo ◽  
Chun-Ching Shih

The present study was designed to evaluate the protective effect of sulphurenic acid (SA), a pure compound from Antrodia camphorata, on diabetes and hyperlipidemia in an animal model study and to clarify the underlying molecular mechanism. Diabetes was induced by daily 55 mg/kg intraperitoneal injections of streptozotocin (STZ) solution over five days. Diabetic mice were randomly divided into six groups and orally gavaged with SA (at three dosages) or glibenclamide (Glib), fenofibrate (Feno) or vehicle for 3 weeks. Our findings showed that STZ-induced diabetic mice had significantly increased fasting blood glucose, glycated hemoglobin (HbA1C), plasma triglyceride (TG), and total cholesterol (TC) levels (p < 0.001, p < 0.001, p < 0.001, and p < 0.05, respectively) but decreased blood insulin, adiponectin, and leptin levels compared to those of the control group (p < 0.001, p < 0.001, and p < 0.001, respectively). Administration of SA to STZ-induced diabetic mice may lower blood glucose but it increased the insulin levels with restoration of the size of the islets of Langerhans cells, implying that SA protected against STZ-induced diabetic states within the pancreas. At the molecular level, SA treatment exerts an increase in skeletal muscle expression levels of membrane glucose transporter 4 (GLUT4) and phospho-Akt to increase the membrane glucose uptake, but the mRNA levels of PEPCK and G6Pase are decreased to inhibit hepatic glucose production, thus leading to its hypoglycemic effect. Moreover, SA may cause hypolipidemic effects not only by enhancing hepatic expression levels of peroxisome proliferator-activated receptor α (PPARα) with increased fatty acid oxidation but also by reducing lipogenic fatty acid synthase (FAS) as well as reducing mRNA levels of sterol regulatory element binding protein (SREBP)1C and SREBP2 to lower blood TG and TC levels. Our findings demonstrated that SA displayed a protective effect against type 1 diabetes and a hyperlipidemic state in STZ-induced diabetic mice.


2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Mei-Hsing Chen ◽  
Cheng-Hsiu Lin ◽  
Chun-Ching Shih

The objective of this study was to evaluate the antihyperlipidemic and antihyperglycemic effects and mechanism of the extract ofClitocybe nuda(CNE), in high-fat- (HF-) fed mice. C57BL/6J was randomly divided into two groups: the control (CON) group was fed with a low-fat diet, whereas the experimental group was fed with a HF diet for 8 weeks. Then, the HF group was subdivided into five groups and was given orally CNE (including C1: 0.2, C2: 0.5, and C3: 1.0 g/kg/day extracts) or rosiglitazone (Rosi) or vehicle for 4 weeks. CNE effectively prevented HF-diet-induced increases in the levels of blood glucose, triglyceride, insulin (P<0.001,P<0.01,P<0.05, resp.) and attenuated insulin resistance. By treatment with CNE, body weight gain, weights of white adipose tissue (WAT) and hepatic triacylglycerol content were reduced; moreover, adipocytes in the visceral depots showed a reduction in size. By treatment with CNE, the protein contents of glucose transporter 4 (GLUT4) were significantly increased in C3-treated group in the skeletal muscle. Furthermore, CNE reduces the hepatic expression of glucose-6-phosphatase (G6Pase) and glucose production. CNE significantly increases protein contents of phospho-AMP-activated protein kinase (AMPK) in the skeletal muscle and adipose and liver tissues. Therefore, it is possible that the activation of AMPK by CNE leads to diminished gluconeogenesis in the liver and enhanced glucose uptake in skeletal muscle. It is shown that CNE exhibits hypolipidemic effect in HF-fed mice by increasing ATGL expression, which is known to help triglyceride to hydrolyze. Moreover, antidiabetic properties of CNE occurred as a result of decreased hepatic glucose production via G6Pase downregulation and improved insulin sensitization. Thus, amelioration of diabetic and dyslipidemic states by CNE in HF-fed mice occurred by regulation of GLUT4, G6Pase, ATGL, and AMPK phosphorylation.


2007 ◽  
Vol 67 (7) ◽  
pp. 2964-2971 ◽  
Author(s):  
Weibo Zhou ◽  
Wan Fang Han ◽  
Leslie E. Landree ◽  
Jagan N. Thupari ◽  
Michael L. Pinn ◽  
...  

2008 ◽  
Vol 36 (01) ◽  
pp. 81-93 ◽  
Author(s):  
Myung-Sook Choi ◽  
Un Ju Jung ◽  
Hye-Jin Kim ◽  
Gyeong-Min Do ◽  
Seon-Min Jeon ◽  
...  

This study examined the effect of a Du-zhong (Eucommia ulmoides Oliver) leaf extract (0.175 g/100 g diet) that was supplemented with a high-fat diet (10% coconut oil, 0.2% cholesterol, wt/wt) on hyperlipidemic hamsters. Hamsters fed with Du-zhong leaf extract for 10 weeks showed a smaller size of epididymal adipocytes compared to the control group. The supplementation of the Du-zhong leaf extract significantly lowered the plasma levels of triglyceride, total cholesterol, LDL-cholesterol, non HDL-cholesterol, and free fatty acid, whereas it elevated the HDL-cholesterol/total cholesterol ratio and apolipoprotein A-I levels. The hepatic cholesterol concentration was lower in the Du-zhong group than in the control group. The plasma total cholesterol concentration was positively correlated with hepatic HMG- CoA reductase activity (r = 0.547, p < 0.05) and hepatic cholesterol concentration (r = 0.769, p < 0.001). The hepatic fatty acid synthase and HMG- CoA reductase activities were significantly lowered by a Du-zhong leaf extract supplement in high fat-fed hamsters. Hepatic fatty acid synthase activity was positively correlated with plasma fatty acid concentration (r = 0.513, p < 0.05) that was lower in the Du-zhong group. These results demonstrate that the Du-zhong leaf extract exhibits antihyperlipidemic properties by suppressing hepatic fatty acid and cholesterol biosynthesis with the simultaneous reduction of plasma and hepatic lipids in high fat-fed hamsters.


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