There are reports of early evidence that suggest the involvement of chronic low-grade inflammation in the pathogenesis of Type 2 diabetes. Thus, substances that have effects in reducing inflammation could be potential drugs for Type 2 diabetes. Leonurine (4-guanidino-n-butyl syringate; SCM-198) is an alkaloid in HL (Herba leonuri), which was reported to possess anti-inflammatory properties. We hypothesize that SCM-198 may have beneficial effects on Type 2 diabetes. In the present study, we attempted to test this hypothesis by evaluating the anti-diabetic effect of SCM-198 and the possible underlying mechanisms of its effects in db/db mice. SCM-198 (50, 100 and 200 mg/kg of body weight), pioglitazone (50 mg/kg of body weight, as a positive control) or 1% CMC-Na (sodium carboxymethylcellulose) were administered to the db/db or db/m mice once daily for 3 weeks. After 3 weeks, SCM-198 (200 mg/kg of body weight) treatment significantly reduced the fasting blood glucose level and increased the plasma insulin concentration in the db/db mice, meanwhile it significantly lowered the plasma TAG (triacylglycerol) concentration and increased the HDL (high-density lipoprotein)-cholesterol concentration. Moreover, the dysregulated transcription of the hepatic glucose metabolic enzymes, including GK (glucokinase), G6Pase (glucose-6-phosphatase) and PEPCK (phosphoenolpyruvate carboxykinase), was recovered by an Akt-dependent pathway. The pro-inflammatory mediators {such as TNFα (tumour necrosis factor α), IL (interleukin)-6, IL-1β, degradation of IκB [inhibitor of NF-κB (nuclear factor-κB)] α and thereafter activation of NF-κB} were reversed by SCM-198 treatment in the db/db mice. The present study provides first evidence that SCM-198 exhibits anti-inflammatory activity and has an ameliorating effect on diabetic symptoms via inhibiting of NF-κB/IKK (IκB kinase) pathway. Consequently, we suggest that SCM-198 may be a prospective agent for prevention and/or moderation of the progress of Type 2 diabetes.
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Research Article|
November 21 2011
Novel anti-diabetic effect of SCM-198 via inhibiting the hepatic NF-κB pathway in db/db mice
Hui Huang;
Hui Huang
1Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai Chempartner Co. Ltd, Shanghai 201203, People's Republic of China
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Hong Xin;
Hong Xin
1Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai Chempartner Co. Ltd, Shanghai 201203, People's Republic of China
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Xinhua Liu;
Xinhua Liu
1Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai Chempartner Co. Ltd, Shanghai 201203, People's Republic of China
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Yajun Xu;
Yajun Xu
1Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai Chempartner Co. Ltd, Shanghai 201203, People's Republic of China
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Danyi Wen;
Danyi Wen
1Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai Chempartner Co. Ltd, Shanghai 201203, People's Republic of China
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Yahua Zhang;
Yahua Zhang
1Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai Chempartner Co. Ltd, Shanghai 201203, People's Republic of China
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Yi Zhun Zhu
Yi Zhun Zhu
1
1Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai Chempartner Co. Ltd, Shanghai 201203, People's Republic of China
1To whom correspondence should be addressed (email zhuyz@fudan.edu.cn).
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Publisher: Portland Press Ltd
Received:
February 16 2011
Revision Received:
July 26 2011
Accepted:
August 23 2011
Accepted Manuscript online:
August 23 2011
Online ISSN: 1573-4935
Print ISSN: 0144-8463
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biosci Rep (2012) 32 (2): 185–195.
Article history
Received:
February 16 2011
Revision Received:
July 26 2011
Accepted:
August 23 2011
Accepted Manuscript online:
August 23 2011
Citation
Hui Huang, Hong Xin, Xinhua Liu, Yajun Xu, Danyi Wen, Yahua Zhang, Yi Zhun Zhu; Novel anti-diabetic effect of SCM-198 via inhibiting the hepatic NF-κB pathway in db/db mice. Biosci Rep 1 April 2012; 32 (2): 185–195. doi: https://doi.org/10.1042/BSR20110017
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