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

Abstract

BackgroundIt 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.MethodsWe 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.ResultsCordycepin inhibited the production of NO and pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α in LPS-activated macrophages via suppressing protein expression of pro-inflammatory mediators. T2D regulating genes such as 11β-HSD1 and PPARγ 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-κB activation in LPS-activated macrophages.ConclusionBased on these observations, cordycepin suppressed T2D regulating genes through the inactivation of NF-κB dependent inflammatory responses and suggesting that cordycepin will provide potential use as an immunomodulatory agent for treating immunological diseases.

Cordycepin prevented IL-β-induced expression of inflammatory mediators in human osteoarthritis chondrocytes

“…In this study, we demonstrated that cordycepin prevented IL-1β-induced NO production as well as iNOS expression at the mRNA and protein levels in human OA chondrocytes. Results were consistent with Seulmee et al's results [17]. They found that cordycepin could inhibit NO production as well as iNOS expression on lipopolysaccharide-induced inflammation in RAW 264.7 cells.…”

“…Our results were consistent with the research from Noh et al [16], who found no significant change RA synovial fibroblast cell viability following treatment with cordycepin (50 uM or 100 uM). Also, Seulmee et al [17] showed that the exposure of mouse leukaemic monocyte macrophage cell line (RAW 264.7) to cordycepin at 5∼40 μg/ml for 24 hours showed no significant adverse effect on cell viability versus the untreated control.…”

“…Noh et al [16] demonstrated that cordycepin has anti-rheumatic and antiinflammatory effects on IL1β-stimulated rheumatoid arthritis synovial fibroblasts (RASFs). Shin et al [17] discovered that cordycepin could suppress expression of diabetes-regulating genes by inhibiting lipopolysaccharide-induced inflammation in macrophages.…”

Suppression of α-MSH and IBMX-induced melanogenesis by cordycepin via inhibition of CREB and MITF, and activation of PI3K/Akt and ERK-dependent mechanisms

“…Cordycepin is extracted from fungi of genus Cordyceps, and has been used traditionally as an anti-tumor, anti-viral, anti-inflammatory agent in East Asian countries (21)(22)(23)(24)(25)(26). In this study, we examined the inhibitory effect of cordycepin on the melanogenesis signaling pathways, including the expression of MITF, tyrosinase, TRP1 and TRP2, and the phosphorylation of CREB, via the activation of ERK and Akt in murine B16F10 melanoma cells stimulated by α-MSH and IBMX.…”

Suppressing effect of cordycepin on the lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells

“…In China, it has been used as a traditional medicine and health food since ancient times. C. militaris has been reported to have beneficial functional effects such as anti-angiogenesis, 6) anti-tumor, anti-diabetic 7) , and hypoglycemic effects 8) . Cordycepin, a characteristic functional component of C. militaris, has been shown to have anti-inflammatory effects.…”