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Tormentic Acid, a Major Component of Suspension Cells of Eriobotrya japonica, Suppresses High-Fat Diet-Induced Diabetes and Hyperlipidemia by Glucose Transporter 4 and AMP-Activated Protein Kinase Phosphorylation

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‡ †Graduate Institute of Pharmaceutical Chemistry and ‡Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung City 40402, Taiwan
§ Department of Internal Medicine, Fong-Yuan Hospital, Department of Health, Executive Yuan, Fong-Yuan District, Taichung City 42055, Taiwan
# Jen Li Biotech Company Ltd., Taiping District, Taiping City 41143, Taiwan
⊥ Graduate Institute of Pharmaceutical Science and Technology, College of Health Science, Central Taiwan University of Science and Technology, No. 666 Buzih Road, Beitun District, Taichung City 40601, Taiwan
*(C.-C.S.) Phone:+886-4-22391647, ext. 3978. Fax: +886-4-22394256. E-mail: [email protected]
Cite this: J. Agric. Food Chem. 2014, 62, 44, 10717–10726
Publication Date (Web):October 15, 2014
https://doi.org/10.1021/jf503334d
Copyright © 2014 American Chemical Society
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    Abstract

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    This study was designed to evaluate the effects and mechanism of tormentic acid (PTA) on diabetes and dyslipidemia in high-fat (HF)-fed mice. Feeding C57BL/6J mice with a HF diet for 12 weeks induced type 2 diabetes and hyperlipidemia. During the last 4 weeks, the mice were given orally PTA (at two dosages) or rosiglitazone (Rosi) or water. In this study, the HF diet increased glucose, triglyceride, insulin, and leptin levels, whereas PTA effectively prevented these phenomena and ameliorated insulin resistance. PTA reduced visceral fat mass and hepatic triacylglycerol contents; moreover, PTA significantly decreased both the area of adipocytes and ballooning degeneration of hepatocytes. PTA caused increased skeletal muscular AMP-activated protein kinase (AMPK) phosphorylation and Akt phosphorylation and glucose transporter 4 (GLUT4) proteins, but reduced the hepatic expressions of phosphenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6 Pase) genes. PTA enhanced skeletal muscular Akt phosphorylation and increased insulin sensitivity. PTA also enhanced phospho-AMPK in the liver. Therefore, it is possible that the activation of AMPK by PTA results in decreasing hepatic glucose production while increasing skeletal muscular GLUT4 contents, thus contributing to attenuating the diabetic state. Moreover, PTA exhibits an antihyperlipidemic effect by down-regulations of the hepatic sterol regulatory element binding protein-1c (SREBP-1c) and apolipoprotein C-III (apo C-III) and an increased peroxisome proliferator activated receptor (PPAR)-α expression, thus resulting in decreases in blood triglycerides. These findings demonstrated that PTA was effective for the treatment of diabetes and hyperlipidemia in HF-fed mice.

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