Cordycepin Suppresses Expression of Diabetes Regulating Genes by Inhibition of Lipopolysaccharide-induced Inflammation in Macrophages.
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-1beta, IL-6, and TNF-alpha in LPS-activated macrophages via suppressing protein expression of pro-inflammatory mediators. T2D regulating genes such as 11beta-HSD1 and PPARgamma 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-kappaB activation in LPS-activated macrophages.


CONCLUSIONS
Based on these observations, cordycepin suppressed T2D regulating genes through the inactivation of NF-kappaB dependent inflammatory responses and suggesting that cordycepin will provide potential use as an immunomodulatory agent for treating immunological diseases.
Shin
Seulmee
S
College of Pharmacy, Sahmyook University, Seoul, Korea.
Lee
Sungwon
S
Kwon
Jeonghak
J
Moon
Sunhee
S
Lee
Seungjeong
S
Lee
Chong-Kil
CK
Cho
Kyunghae
K
Ha
Nam-Joo
NJ
Kim
Kyungjae
K