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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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Effects of cordycepin on LPS-induced mitogen-activated protein kinase phosphorylation in RAW 264.7 macrophages.Notes: Cells were treated with 100 ng/mL LPS for the indicated times (A) or treated with different concentrations of cordycepin 1 hour before LPS treatment for 30 minutes (B). Total proteins were prepared and separated on 10% sodium dodecyl sulfate-polyacrylamide gels, followed by Western blotting using the indicated antibodies.Abbreviations: ERK, extracellular signal-regulated kinase; JNK, c-Jun N-terminal kinase; LPS, lipopolysaccharide.
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f4-dddt-8-1941: Effects of cordycepin on LPS-induced mitogen-activated protein kinase phosphorylation in RAW 264.7 macrophages.Notes: Cells were treated with 100 ng/mL LPS for the indicated times (A) or treated with different concentrations of cordycepin 1 hour before LPS treatment for 30 minutes (B). Total proteins were prepared and separated on 10% sodium dodecyl sulfate-polyacrylamide gels, followed by Western blotting using the indicated antibodies.Abbreviations: ERK, extracellular signal-regulated kinase; JNK, c-Jun N-terminal kinase; LPS, lipopolysaccharide.

Mentions: Because MAPK signaling molecules also play a critical role in regulating the LPS-induced inflammatory process, we analyzed the phosphorylation levels of MAPKs in LPS-treated RAW 264.7 cells by Western blotting. As depicted in Figure 4, phosphorylation of p38 MAPK, ERK, and JNK by LPS stimulation occurred at 15 minutes and was sustained until 1–2 hours; however, pretreatment with cordycepin significantly suppressed phosphorylation in a concentration-dependent manner. In contrast, the levels of total MAPK proteins were unaffected by either LPS or cordycepin treatment, suggesting that inactivation of MAPK signaling may be involved in the inhibitory effect of cordycepin on the production of LPS-induced proinflammatory mediators and cytokines in RAW 264.7 cells.


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 on LPS-induced mitogen-activated protein kinase phosphorylation in RAW 264.7 macrophages.Notes: Cells were treated with 100 ng/mL LPS for the indicated times (A) or treated with different concentrations of cordycepin 1 hour before LPS treatment for 30 minutes (B). Total proteins were prepared and separated on 10% sodium dodecyl sulfate-polyacrylamide gels, followed by Western blotting using the indicated antibodies.Abbreviations: ERK, extracellular signal-regulated kinase; JNK, c-Jun N-terminal kinase; LPS, lipopolysaccharide.
© Copyright Policy
Related In: Results  -  Collection

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

f4-dddt-8-1941: Effects of cordycepin on LPS-induced mitogen-activated protein kinase phosphorylation in RAW 264.7 macrophages.Notes: Cells were treated with 100 ng/mL LPS for the indicated times (A) or treated with different concentrations of cordycepin 1 hour before LPS treatment for 30 minutes (B). Total proteins were prepared and separated on 10% sodium dodecyl sulfate-polyacrylamide gels, followed by Western blotting using the indicated antibodies.Abbreviations: ERK, extracellular signal-regulated kinase; JNK, c-Jun N-terminal kinase; LPS, lipopolysaccharide.
Mentions: Because MAPK signaling molecules also play a critical role in regulating the LPS-induced inflammatory process, we analyzed the phosphorylation levels of MAPKs in LPS-treated RAW 264.7 cells by Western blotting. As depicted in Figure 4, phosphorylation of p38 MAPK, ERK, and JNK by LPS stimulation occurred at 15 minutes and was sustained until 1–2 hours; however, pretreatment with cordycepin significantly suppressed phosphorylation in a concentration-dependent manner. In contrast, the levels of total MAPK proteins were unaffected by either LPS or cordycepin treatment, suggesting that inactivation of MAPK signaling may be involved in the inhibitory effect of cordycepin on the production of LPS-induced proinflammatory mediators and cytokines in RAW 264.7 cells.

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