| Background and purpose:There are reports of early evidence that suggested the involvement of chronic low-grade inflammation in the pathogenesis of type 2 diabetes, which plays a key role in type 2 diabetes. Thus, substances that have effects in reducing inflammation could be potential drugs for type 2 diabetes. Leonurine (SCM-198) is an alkaloid in Herba leonuri, which was reported to possess anti-inflammatory property. We hypothesize that SCM-198 may have beneficial effect on type 2 diabetes. In this 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.Experimental approach:SCM-198 (50,100,200 mg/kg body weight), pioglitazone (as positive control) (50 mg/kg body weight) and 1% sodium carboxymethyl cellulose (CMC-Na) were administered to the db/db or db/m mice once daily for 3 weeks.Key results:After 3 weeks, SCM-198 (200 mg/kg) treatment significantly reduced the fasting blood glucose level and increased the plasma insulin concentration in the db/db mice, meanwhile it significantly lowered and increased the plasma triglyceride and HDL-cholesterol concentration respectively. Moreover, the disregulated transcription of the hepatic glucose metabolic enzymes was corrected, and the phosphoration of Akt and insulin receptor (IR) were recovered, with an increase of Foxol phosphorylations. The proinflammatory mediators (like TNF-α, IL-6, IL-1β, degradation of IκB-αand thereafter activation of NF-κB) were reversed by SCM-198 treatment in the db/db mice.Conclusions and implications:The present study found that SCM-198 exhibited anti-inflammatory activity and has an ameliorating effect on diabetic symptoms involving inhibition of NF-κB/IKK pathway. Consequently, we suggested that SCM-198 may be a prospective agent for prevention and/or moderation of the progress of type 2 diabetes. |
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