Ergostatrien-3β-ol from Antrodia camphorata Inhibits Diabetes and Hyperlipidemia in High-Fat-Diet Treated Mice via Regulation of Hepatic Related Genes, Glucose Transporter 4, and AMP-Activated Protein Kinase Phosphorylation

Abstract

This study was designed to explore the effects and mechanism of ergostatrien-3β-ol (EK100) from the submerged whole broth of Antrodia camphorata on diabetes and dyslipidemia in high fat diet (HFD)-fed mice for 12 weeks. The C57BL/6J mouse fed with a high fat diet (HFD) could induce insulin resistance and hyperlipidemia. After 8 week of induction, mice were receiving EK100 (at three dosages) or fenofibrate (Feno) or rosiglitazone (Rosi) or vehicle by oral gavage 4 weeks afterward. HFD-fed mice display increased blood glucose, glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), insulin, and leptin levels. These blood markers were significantly lower in EK100-treated mice, and finally ameliorated insulin resistance. EK100 treatment exhibited reduced hepatic ballooning degeneration and size of visceral adipocytes. Glucose transporter 4 (GLUT4) proteins and phosphorylation of Akt in skeletal muscle were significantly increased in EK100- and Rosi-treated mice. EK100, Feno, and Rosi treatment led to significant increases in phosphorylation of AMP-activated protein kinase (phospho-AMPK) protein in both skeletal muscle and liver. Moreover, EK100 caused a decrease in hepatic expressions of phosphenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6 Pase), and decreased glucose production. EK100 lowered blood TG level by inhibition of hepatic fatty acid synthesis by dampening sterol response element binding protein-1c (SREBP-1c) but increasing expression of peroxisome proliferator activated receptor α (PPARα). Moreover, EK100-treated mice reduced blood TC levels by decreased hepatic expressions of SREBP2, which plays a major role in the regulation of cholesterol synthesis. EK100 increased high-density lipoprotein cholesterol (HDL-C) concentrations by increasing expressions of apolipoprotein A-I (apo A-I) in liver tissue. Our findings manifest that EK100 may have therapeutic potential in treating type 2 diabetes associated with hyperlipidemia in HFD-fed mice by regulation of GLUT4, PEPCK, G6 Pase, SREBP1c, SREBP2, apo A-I, and AMPK phosphorylation.

(−)-Epicatechin-3-O-β-D-allopyranoside from Davallia formosana prevents diabetes and dyslipidemia in streptozotocin-induced diabetic mice

“…The levels of TG and TC were measured using commercial assay kits in accordance with manufacturer directions (Triglycerides-E test and Cholesterol-E test, Wako Pure Chemical, Osaka, Japan). Aliquots of plasma samples (>25 μL) were used for insulin, leptin, and adiponectin levels by enzyme-linked immunosorbent assay (ELISA) kits (mouse insulin ELISA kit, Mercodia, Uppsala, Sweden; mouse leptin ELISA kit, Morinaga, Yokohama, Japan) as previous procedures [24–26]. Percent HbA1c was measured with a Hemoglobin A 1C kit (BioSystems S.A., Barcelona, Spain).…”

“…Parts of liver and pancreas specimens were fixed with formalin (200 g/kg) neutral buffered solution and embedded in paraffin and sections (8 μm) were cut and stained with hematoxylin and eosin and images were photographed in accordance with previous reports [24–26]. Ballooning degeneration is investigated in the liver of mice.…”

“…Relative mRNA quantification (primers are described in Table 1) and immunoblots for measurement of muscle membrane GLUT4 and hepatic phospho-AMPK (Thr 172 ) and phospho-Akt (Ser 473 ) proteins were performed as described in previously reported studies [24–26]. Liver tissue was analyzed for PPARα and FAS protein content.…”

“…The resulting pellet was resuspended in a small amount of buffer (about 0.5 mL) as a total membrane fraction [27,28]. The expression levels of GLUT4, phospho-AMPK, and total AMPK were determined by Western blotting as previously described [25,26]. …”

A mechanistic study on the biosynthetic regulation of bioactive metabolite Antroquinonol from edible and medicinal mushroom Antrodia camphorata

“…Previous studies have indicated that A. camphorata exhibits many physiological and pharmacological properties. Many types of bioactive compounds have been isolated from A. camphorata, such as triterpenoids, polysaccharides, ergostanoids, succinic and maleic derivatives, benzenoids, and ubiquinone derivatives (Chang et al, 2015a;Chang, Kuo, Chang, & Kong, 2015b;Chien et al, 2008;Huang et al, 2015;Kuo, Lin, & Shih, 2015;Yen et al, 2015). Antroquinonol, an ubquinone derivative, is one of the most important bioactive compounds isolated from the mycelia and fruiting bodies of A. camphorata produced by solid-state fermentation (Lee, Lee, & Tsou, 2007).…”