Role of Cordycepin and Adenosine on the Phenotypic Switch of Macrophages via Induced Anti-inflammatory Cytokines

Abstract

BackgroundChronic low grade inflammation is closely linked to type II diabetes, obesity, and atherosclerosis. Macrophages play a key role in the regulation of pro- or anti-inflammatory actions at the lesion sites of disease. Components of cordyceps militaris, cordycepin and adenosine, have been used for the modulation of inflammatory diseases. The effects of cordycepin in the modulation of macrophages have yet to be elucidated. We investigated the effects of cordycepin and adenosine on the morphological changes of macrophages under the inflammatory condition of LPS and an anti-inflammatory condition involving high concentrations of adenosine.MethodsWe confirmed the mRNA levels of the M1/M2 cytokine genes through RT-PCR and morphological change.ResultsLPS-activated macrophages returned to their inactivated original shape, i.e., they looked like naïve macrophages, through the treatment with high concentrations of cordycepin (40 µg/ml). LPS and adenosine activated macrophages also returned to their original inactivated shapes after cordycepin treatment; however, at relatively higher levels of cordycepin than adenosine. This change did not occur with relatively low concentrations of cordycepin. Adenosine down-regulated the gene expression of M1 cytokines (IL-1β, TNF-α) and chemokines (CX3CR1, RANTES), as well as cordycepin. Additionally, M2 cytokines (IL-10, IL-1ra, TGF-β) were up-regulated by both cordycepin and adenosine.ConclusionBased on these observations, both cordycepin and adenosine regulated the phenotypic switch on macrophages and suggested that cordycepin and adenosine may potentially be used as immunomodulatory agents in the treatment of inflammatory disease.

Cordyceps militaris extract suppresses dextran sodium sulfate-induced acute colitis in mice and production of inflammatory mediators from macrophages and mast cells

“…In our DSS-induced acute colitis models, CM extract not only suppressed colonic infiltration of inflammatory cells, but also inhibited intestinal expression of pro-inflammatory cytokines, such as IL-1 and TNF-␣. As reported in a previous study, agents capable of blocking inflammatory cascades have potential in prevention and treatment of IBD (Barrie and Regueiro, 2007).Several groups demonstrated that Cordyceps militaris comprised of numerous components including cordycepin (Kim et al, 2006), adenosine (Shin et al, 2009), and polysaccharide (Yu et al, 2004), which have anti-inflammatory activities. Further studies will explore the effect of active components including cordycepin in Cordyceps militaris in acute colitis model.…”

“…Sustained high NO production in the colon plays a role in the pathology of IBD. Several studies have shown that CM extract suppresses iNOS expression and NO production in macrophages (Kim et al, 2006;Shin et al, 2009). The previous study demonstrated that the severity of DSSinduced colitis was significantly attenuated in iNOS knockout and in specific iNOS-inhibitor treated animals (Krieglstein et al, 2001).…”

“…Recent studies have demonstrated that Cordyceps militaris extracts exerted strong anti-inflammatory (Lin et al, 2001) and anti-cancer activities (Hsu et al, 2008). Alleviation of several inflammatory diseases by Cordyceps militaris was achieved through decrease of the levels of iNOS (Won and Park, 2005) and TNF-␣ proteins (Ohta et al, 2007;Shin et al, 2009). Adenosine, and polysaccharide (Yu et al, 2004), which have anti-inflammatory activities, are the major biological components of Cordyceps militaris.…”

The effect of polymer degradation time on functional outcomes of temporary elastic patch support in ischemic cardiomyopathy

“…Furthermore, the ratio of CD163 to CD68, the latter being a pan macrophage marker [45,46], was also greater in the PECUU group. M2 macrophages have been reported to produce TGF-β [47,48], which has been described as a multipotent cytokine with healing potential in various tissues by promoting cell growth and matrix accumulation, thus facilitating the ability of tissue to withstand stress without expanding [49]. Although the segregation of macrophages into two distinct phenotypes is a simplified framework of the in vivo reality, our findings may suggest that epicardial implantation of a patch with a moderate degradation rate has beneficial impact on infarct tissue healing through M2 polarization.…”

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.…”