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Anti-inflammatory effects of cordycepin in lipopolysaccharide-stimulated RAW 264.7 macrophages through Toll-like receptor 4-mediated suppression of mitogen-activated protein kinases and NF-κB signaling pathways.

Choi YH, Kim GY, Lee HH - Drug Des Devel Ther (2014)

Bottom Line: This compound possesses many pharmacological properties, such as an ability to enhance immune function, as well as antioxidant, antiaging, and anticancer effects.In addition, pretreatment with cordycepin significantly inhibited lipopolysaccharide (LPS)-induced phosphorylation of mitogen-activating protein kinases and attenuated nuclear translocation of NF-κB by LPS, which was associated with abrogation of inhibitor kappa B-alpha degradation.Taken together, the results suggest that the inhibitory effects of cordycepin on LPS-stimulated inflammatory responses in RAW 264.7 macrophages are associated with suppression of mitogen-activating protein kinases and activation of NF-κB by inhibition of the Toll-like receptor 4 signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan, Republic of Korea ; Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan, Republic of Korea.

ABSTRACT
Cordycepin is the main functional component of the Cordyceps species, which has been widely used in traditional Oriental medicine. This compound possesses many pharmacological properties, such as an ability to enhance immune function, as well as antioxidant, antiaging, and anticancer effects. In the present study, we investigated the anti-inflammatory effects of cordycepin using a murine macrophage RAW 264.7 cell model. Our data demonstrated that cordycepin suppressed production of proinflammatory mediators such as nitric oxide (NO) and prostaglandin E2 by inhibiting inducible NO synthase and cyclooxygenase-2 gene expression. Cordycepin also inhibited the release of proinflammatory cytokines, including tumor necrosis factor-alpha and interleukin-1-beta, through downregulation of respective mRNA expression. In addition, pretreatment with cordycepin significantly inhibited lipopolysaccharide (LPS)-induced phosphorylation of mitogen-activating protein kinases and attenuated nuclear translocation of NF-κB by LPS, which was associated with abrogation of inhibitor kappa B-alpha degradation. Furthermore, cordycepin potently inhibited the binding of LPS to macrophages and LPS-induced Toll-like receptor 4 and myeloid differentiation factor 88 expression. Taken together, the results suggest that the inhibitory effects of cordycepin on LPS-stimulated inflammatory responses in RAW 264.7 macrophages are associated with suppression of mitogen-activating protein kinases and activation of NF-κB by inhibition of the Toll-like receptor 4 signaling pathway.

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Related in: MedlinePlus

Effects of cordycepin, CLI-095, and LPS on viability of RAW 264.7 macrophages. The cells were treated with the indicated concentrations of cordycepin, CLI-095, or LPS alone, or pretreated with cordycepin or CLI-095 for 1 hour before LPS treatment. Cell viability was assessed after 24 hours using MTT reduction assays. The data are shown as the mean ± standard deviation of three independent experiments.Abbreviation: LPS, lipopolysaccharide.
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f8-dddt-8-1941: Effects of cordycepin, CLI-095, and LPS on viability of RAW 264.7 macrophages. The cells were treated with the indicated concentrations of cordycepin, CLI-095, or LPS alone, or pretreated with cordycepin or CLI-095 for 1 hour before LPS treatment. Cell viability was assessed after 24 hours using MTT reduction assays. The data are shown as the mean ± standard deviation of three independent experiments.Abbreviation: LPS, lipopolysaccharide.

Mentions: Finally, to examine whether cordycepin or CLI-095 is cytotoxic to RAW 264.7 cells, the cells were exposed to cordycepin alone and together with CLI-095 for 24 hours in the presence or absence of LPS, and cell viability was measured by the MTT assay. The results showed no cytotoxic effects within our tested concentrations (Figure 8). These results clearly indicate that the anti-inflammatory activity of cordycepin in LPS-stimulated RAW 264.7 macrophages was not due to cytotoxicity.


Anti-inflammatory effects of cordycepin in lipopolysaccharide-stimulated RAW 264.7 macrophages through Toll-like receptor 4-mediated suppression of mitogen-activated protein kinases and NF-κB signaling pathways.

Choi YH, Kim GY, Lee HH - Drug Des Devel Ther (2014)

Effects of cordycepin, CLI-095, and LPS on viability of RAW 264.7 macrophages. The cells were treated with the indicated concentrations of cordycepin, CLI-095, or LPS alone, or pretreated with cordycepin or CLI-095 for 1 hour before LPS treatment. Cell viability was assessed after 24 hours using MTT reduction assays. The data are shown as the mean ± standard deviation of three independent experiments.Abbreviation: LPS, lipopolysaccharide.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4206205&req=5

f8-dddt-8-1941: Effects of cordycepin, CLI-095, and LPS on viability of RAW 264.7 macrophages. The cells were treated with the indicated concentrations of cordycepin, CLI-095, or LPS alone, or pretreated with cordycepin or CLI-095 for 1 hour before LPS treatment. Cell viability was assessed after 24 hours using MTT reduction assays. The data are shown as the mean ± standard deviation of three independent experiments.Abbreviation: LPS, lipopolysaccharide.
Mentions: Finally, to examine whether cordycepin or CLI-095 is cytotoxic to RAW 264.7 cells, the cells were exposed to cordycepin alone and together with CLI-095 for 24 hours in the presence or absence of LPS, and cell viability was measured by the MTT assay. The results showed no cytotoxic effects within our tested concentrations (Figure 8). These results clearly indicate that the anti-inflammatory activity of cordycepin in LPS-stimulated RAW 264.7 macrophages was not due to cytotoxicity.

Bottom Line: This compound possesses many pharmacological properties, such as an ability to enhance immune function, as well as antioxidant, antiaging, and anticancer effects.In addition, pretreatment with cordycepin significantly inhibited lipopolysaccharide (LPS)-induced phosphorylation of mitogen-activating protein kinases and attenuated nuclear translocation of NF-κB by LPS, which was associated with abrogation of inhibitor kappa B-alpha degradation.Taken together, the results suggest that the inhibitory effects of cordycepin on LPS-stimulated inflammatory responses in RAW 264.7 macrophages are associated with suppression of mitogen-activating protein kinases and activation of NF-κB by inhibition of the Toll-like receptor 4 signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan, Republic of Korea ; Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan, Republic of Korea.

ABSTRACT
Cordycepin is the main functional component of the Cordyceps species, which has been widely used in traditional Oriental medicine. This compound possesses many pharmacological properties, such as an ability to enhance immune function, as well as antioxidant, antiaging, and anticancer effects. In the present study, we investigated the anti-inflammatory effects of cordycepin using a murine macrophage RAW 264.7 cell model. Our data demonstrated that cordycepin suppressed production of proinflammatory mediators such as nitric oxide (NO) and prostaglandin E2 by inhibiting inducible NO synthase and cyclooxygenase-2 gene expression. Cordycepin also inhibited the release of proinflammatory cytokines, including tumor necrosis factor-alpha and interleukin-1-beta, through downregulation of respective mRNA expression. In addition, pretreatment with cordycepin significantly inhibited lipopolysaccharide (LPS)-induced phosphorylation of mitogen-activating protein kinases and attenuated nuclear translocation of NF-κB by LPS, which was associated with abrogation of inhibitor kappa B-alpha degradation. Furthermore, cordycepin potently inhibited the binding of LPS to macrophages and LPS-induced Toll-like receptor 4 and myeloid differentiation factor 88 expression. Taken together, the results suggest that the inhibitory effects of cordycepin on LPS-stimulated inflammatory responses in RAW 264.7 macrophages are associated with suppression of mitogen-activating protein kinases and activation of NF-κB by inhibition of the Toll-like receptor 4 signaling pathway.

Show MeSH
Related in: MedlinePlus