(-)-Epicatechin-3-O-β-D-allopyranoside from Davallia formosana, Prevents Diabetes and Hyperlipidemia by Regulation of Glucose Transporter 4 and AMP-Activated Protein Kinase Phosphorylation in High-Fat-Fed Mice.
The purpose of this experiment was to determine the antidiabetic and lipid-lowering effects of (-)-epicatechin-3-O-β-D-allopyranoside (BB) from the roots and stems of Davallia formosana in mice. Animal treatment was induced by high-fat diet (HFD) or low-fat diet (control diet, CD). After eight weeks of HFD or CD exposure, the HFD mice were treating with BB or rosiglitazone (Rosi) or fenofibrate (Feno) or water through gavage for another four weeks. However, at 12 weeks, the HFD-fed group had enhanced blood levels of glucose, triglyceride (TG), and insulin. BB treatment significantly decreased blood glucose, TG, and insulin levels. Moreover, visceral fat weights were enhanced in HFD-fed mice, accompanied by increased blood leptin concentrations and decreased adiponectin levels, which were reversed by treatment with BB. Muscular membrane protein levels of glucose transporter 4 (GLUT4) were reduced in HFD-fed mice and significantly enhanced upon administration of BB, Rosi, and Feno. Moreover, BB treatment markedly increased hepatic and skeletal muscular expression levels of phosphorylation of AMP-activated (adenosine monophosphate) protein kinase (phospho-AMPK). BB also decreased hepatic mRNA levels of phosphenolpyruvate carboxykinase (PEPCK), which are associated with a decrease in hepatic glucose production. BB-exerted hypotriglyceridemic activity may be partly associated with increased mRNA levels of peroxisome proliferator activated receptor α (PPARα), and with reduced hepatic glycerol-3-phosphate acyltransferase (GPAT) mRNA levels in the liver, which decreased triacylglycerol synthesis. Nevertheless, we demonstrated BB was a useful approach for the management of type 2 diabetes and dyslipidemia in this animal model.
Graduate Institute of Pharmaceutical Science and Technology, College of Health Science, Central Taiwan University of Science and Technology, Taichung City 40601, Taiwan. ccshih@ctust.edu.tw.
Chun-Ching
CC
Shih
Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung City 40402, Taiwan. jwu@mail.cmu.edu.tw.
Jin-Bin
JB
Wu
Graduate Institute of Pharmaceutical Science and Technology, College of Health Science, Central Taiwan University of Science and Technology, Taichung City 40601, Taiwan. ccshih@ctust.edu.tw.
Jia-Ying
JY
Jian
Department of Internal Medicine, Fong-Yuan Hospital, Department of Health, Executive Yuan, Fong-Yuan District, Taichung City 42055, Taiwan. keny71@pchome.com.tw.
Cheng-Hsiu
CH
Lin
Jen Li Biotech Company Ltd., Taiping District, Taichung City 41143, Taiwan. jlbioaya@gmail.com.
Hui-Ya
HY
Ho
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D011345:Fenofibrate / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D010946:Plants, Medicinal / Q000737:chemistry*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D055372:AMP-Activated Protein Kinases; D011345:Fenofibrate
AMP-activated protein kinase phosphorylation; Davallia formosana; diabetes; glucose transporter 4; hypertriglyceridemia