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Cordycepin Suppresses Expression of Diabetes Regulating Genes by Inhibition of Lipopolysaccharide-induced Inflammation in Macrophages

  • Received : 2009.04.13
  • Accepted : 2009.05.04
  • Published : 2009.06.30
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Abstract

Background: It has been recently noticed that type 2 diabetes (T2D), one of the most common metabolic diseases, causes a chronic low-grade inflammation and activation of the innate immune system that are closely involved in the pathogenesis of T2D. Cordyceps militaris, a traditional medicinal mushroom, produces a component compound, cordycepin (3'-deoxyadenosine). Cordycepin has been known to have many pharmacological activities including immunological stimulating, anti-cancer, and anti-infection activities. The molecular mechanisms of cordycepin in T2D are not clear. In the present study, we tested the role of cordycepin on the anti-diabetic effect and anti-inflammatory cascades in LPS-stimulated RAW 264.7 cells. Methods: We confirmed the levels of diabetes regulating genes mRNA and protein of cytokines through RT-PCR and western blot analysis and followed by FACS analysis for the surface molecules. Results: Cordycepin inhibited the production of NO and pro-inflammatory cytokines such as IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ in LPS-activated macrophages via suppressing protein expression of pro-inflammatory mediators. T2D regulating genes such as $11{\beta}$-HSD1 and PPAR${\gamma}$ were decreased as well as expression of co-stimulatory molecules such as ICAM-1 and B7-1/-2 were also decreased with the increment of its concentration. In accordance with suppressed pro-inflammatory cytokine production lead to inhibition of diabetic regulating genes in activated macrophages. Cordycepin suppressed NF-${\kappa}B$ activation in LPS-activated macrophages. Conclusion: Based on these observations, cordycepin suppressed T2D regulating genes through the inactivation of NF-${\kappa}B$ dependent inflammatory responses and suggesting that cordycepin will provide potential use as an immunomodulatory agent for treating immunological diseases.

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References

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