期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 736, 期 -, 页码 26-34出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2014.04.031
关键词
Diabetes; Inflammation; Oxidative stress; Antioxidant; Thiazole derivative
资金
- Bumsuk Academic Research Fund
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science, and Technology [2012R1A1A2041484]
- Korea Institute of Science and Technology Institutional Program
- National Research Foundation of Korea [2012R1A1A2041484] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Thiazole derivatives are attractive candidates for drug development because they can be efficiently synthesized and are active against a number of diseases and conditions, including diabetes. In our present study, we investigated the anti-inflammatory and antioxidant properties of N-adamantyl-4-methylthiazol-2-amine (KHG26693), a new thiazole derivative, in a streptozotocin (STZ)-induced model of diabetes mellitus. STZ-induced diabetic rats were intraperitoneally administered KHG26693 (3 mg/kg-body weight/day) for 4 weeks. KHG26693 administration significantly decreased blood glucose, triglycerides, and cholesterol and increased insulin. KHG26693 also suppressed several inflammatory responses in STZ-induced diabetic rats, as evidenced by decreased levels of serum tumor necrosis factor-alpha, interleukin-1 beta, and nitric oxide. Additionally, KHG26693 significantly modulated hepatic lipid peroxidation, catalase and superoxide dismutase activity, and the nonenzymatic antioxidant status (e.g., vitamins C and E), and reduced the glutathione content. These anti-inflammatory/antioxidative actions occurred as a result of the downregulation of inducible nitric oxide synthase and nuclear factor-kappa B. Taken together, our results suggest that KHG26693 successfully reduces the production of oxidative stress in STZ-induced diabetic rats by regulating the oxidation reduction system, specifically increasing antioxidant capacity. Furthermore, KHG26693 treatment significantly reverted the key enzymes of glucose metabolism, such as glucokinase, glucose-6-phosphatase, glycogen synthase, glycogen phosphorylase, and fructose-1,6-bisphosphatase, to near-normal levels in liver tissues. These results indicate that KHG26693 normalizes disturbed glucose metabolism by enhancing glucose utilization and decreasing liver glucose production via insulin release, suggesting the possibility of future diabetes treatments. (C) 2014 Elsevier B.V. All rights reserved.
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