Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-κB through Akt and p38 inhibition in RAW 264.7 macrophage cells

Ho Gyoung Kim, Bhushan Shrestha, So Yeon Lim, Deok Hyo Yoon, Woo Chul Chang, Dong Jik Shin, Sang Kuk Han, Sang Min Park, Jung Hee Park, Hae Il Park, Jae Mo Sung, Yangsoo Jang, Namsik Chung, Ki Chul Hwang, Tae Woong Kim

Research output: Contribution to journalArticle

219 Citations (Scopus)

Abstract

Cordyceps militaris, a caterpillar-grown traditional medicinal mushroom, produces an important bioactive compound, cordycepin (3′-deoxyadenosine). Cordycepin is reported to possess many pharmacological activities including immunological stimulating, anti-cancer, anti-virus and anti-infection activities. The molecular mechanisms of cordycepin on pharmacological and biochemical actions of macrophages in inflammation have not been clearly elucidated yet. In the present study, we tested the role of cordycepin on the anti-inflammation cascades in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. In LPS-activated macrophage, nitric oxide (NO) production was inhibited by butanol fraction of C. militaris and the major component of C. militaris butanol faction was identified as cordycepin by high performance liquid chromatography. To investigate the mechanism by which cordycepin inhibits NO production and inducible nitric oxide synthase (iNOS) expression, we examined the activation of Akt and MAP kinases in LPS-activated macrophage. Cordycepin markedly inhibited the phosphorylation of Akt and p38 in dose-dependent manners in LPS-activated macrophage. Moreover, cordycepin suppressed tumor necrosis factor (TNF-α) expression, IκB alpha phosphorylation, and translocation of nuclear factor-κB (NF-κB). The expressions of cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were significantly decreased in RAW 264.7 cell by cordycepin. Taken together, these results suggest that cordycepin inhibits the production of NO production by down-regulation of iNOS and COX-2 gene expression via the suppression of NF-κB activation, Akt and p38 phosphorylation. Thus, cordycepin may provide a potential therapeutic approach for inflammation-associated disorders.

Original languageEnglish
Pages (from-to)192-199
Number of pages8
JournalEuropean Journal of Pharmacology
Volume545
Issue number2-3
DOIs
Publication statusPublished - 2006 Sep 18

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Lipopolysaccharides
Macrophages
Inflammation
Cordyceps
Nitric Oxide Synthase Type II
Nitric Oxide
Butanols
Phosphorylation
RAW 264.7 Cells
cordycepin
Pharmacology
Agaricales
Virus Diseases
Phosphotransferases
Down-Regulation
Tumor Necrosis Factor-alpha
High Pressure Liquid Chromatography
Gene Expression

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Kim, Ho Gyoung ; Shrestha, Bhushan ; Lim, So Yeon ; Yoon, Deok Hyo ; Chang, Woo Chul ; Shin, Dong Jik ; Han, Sang Kuk ; Park, Sang Min ; Park, Jung Hee ; Park, Hae Il ; Sung, Jae Mo ; Jang, Yangsoo ; Chung, Namsik ; Hwang, Ki Chul ; Kim, Tae Woong. / Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-κB through Akt and p38 inhibition in RAW 264.7 macrophage cells. In: European Journal of Pharmacology. 2006 ; Vol. 545, No. 2-3. pp. 192-199.
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abstract = "Cordyceps militaris, a caterpillar-grown traditional medicinal mushroom, produces an important bioactive compound, cordycepin (3′-deoxyadenosine). Cordycepin is reported to possess many pharmacological activities including immunological stimulating, anti-cancer, anti-virus and anti-infection activities. The molecular mechanisms of cordycepin on pharmacological and biochemical actions of macrophages in inflammation have not been clearly elucidated yet. In the present study, we tested the role of cordycepin on the anti-inflammation cascades in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. In LPS-activated macrophage, nitric oxide (NO) production was inhibited by butanol fraction of C. militaris and the major component of C. militaris butanol faction was identified as cordycepin by high performance liquid chromatography. To investigate the mechanism by which cordycepin inhibits NO production and inducible nitric oxide synthase (iNOS) expression, we examined the activation of Akt and MAP kinases in LPS-activated macrophage. Cordycepin markedly inhibited the phosphorylation of Akt and p38 in dose-dependent manners in LPS-activated macrophage. Moreover, cordycepin suppressed tumor necrosis factor (TNF-α) expression, IκB alpha phosphorylation, and translocation of nuclear factor-κB (NF-κB). The expressions of cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were significantly decreased in RAW 264.7 cell by cordycepin. Taken together, these results suggest that cordycepin inhibits the production of NO production by down-regulation of iNOS and COX-2 gene expression via the suppression of NF-κB activation, Akt and p38 phosphorylation. Thus, cordycepin may provide a potential therapeutic approach for inflammation-associated disorders.",
author = "Kim, {Ho Gyoung} and Bhushan Shrestha and Lim, {So Yeon} and Yoon, {Deok Hyo} and Chang, {Woo Chul} and Shin, {Dong Jik} and Han, {Sang Kuk} and Park, {Sang Min} and Park, {Jung Hee} and Park, {Hae Il} and Sung, {Jae Mo} and Yangsoo Jang and Namsik Chung and Hwang, {Ki Chul} and Kim, {Tae Woong}",
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Kim, HG, Shrestha, B, Lim, SY, Yoon, DH, Chang, WC, Shin, DJ, Han, SK, Park, SM, Park, JH, Park, HI, Sung, JM, Jang, Y, Chung, N, Hwang, KC & Kim, TW 2006, 'Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-κB through Akt and p38 inhibition in RAW 264.7 macrophage cells', European Journal of Pharmacology, vol. 545, no. 2-3, pp. 192-199. https://doi.org/10.1016/j.ejphar.2006.06.047

Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-κB through Akt and p38 inhibition in RAW 264.7 macrophage cells. / Kim, Ho Gyoung; Shrestha, Bhushan; Lim, So Yeon; Yoon, Deok Hyo; Chang, Woo Chul; Shin, Dong Jik; Han, Sang Kuk; Park, Sang Min; Park, Jung Hee; Park, Hae Il; Sung, Jae Mo; Jang, Yangsoo; Chung, Namsik; Hwang, Ki Chul; Kim, Tae Woong.

In: European Journal of Pharmacology, Vol. 545, No. 2-3, 18.09.2006, p. 192-199.

Research output: Contribution to journalArticle

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T1 - Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-κB through Akt and p38 inhibition in RAW 264.7 macrophage cells

AU - Kim, Ho Gyoung

AU - Shrestha, Bhushan

AU - Lim, So Yeon

AU - Yoon, Deok Hyo

AU - Chang, Woo Chul

AU - Shin, Dong Jik

AU - Han, Sang Kuk

AU - Park, Sang Min

AU - Park, Jung Hee

AU - Park, Hae Il

AU - Sung, Jae Mo

AU - Jang, Yangsoo

AU - Chung, Namsik

AU - Hwang, Ki Chul

AU - Kim, Tae Woong

PY - 2006/9/18

Y1 - 2006/9/18

N2 - Cordyceps militaris, a caterpillar-grown traditional medicinal mushroom, produces an important bioactive compound, cordycepin (3′-deoxyadenosine). Cordycepin is reported to possess many pharmacological activities including immunological stimulating, anti-cancer, anti-virus and anti-infection activities. The molecular mechanisms of cordycepin on pharmacological and biochemical actions of macrophages in inflammation have not been clearly elucidated yet. In the present study, we tested the role of cordycepin on the anti-inflammation cascades in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. In LPS-activated macrophage, nitric oxide (NO) production was inhibited by butanol fraction of C. militaris and the major component of C. militaris butanol faction was identified as cordycepin by high performance liquid chromatography. To investigate the mechanism by which cordycepin inhibits NO production and inducible nitric oxide synthase (iNOS) expression, we examined the activation of Akt and MAP kinases in LPS-activated macrophage. Cordycepin markedly inhibited the phosphorylation of Akt and p38 in dose-dependent manners in LPS-activated macrophage. Moreover, cordycepin suppressed tumor necrosis factor (TNF-α) expression, IκB alpha phosphorylation, and translocation of nuclear factor-κB (NF-κB). The expressions of cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were significantly decreased in RAW 264.7 cell by cordycepin. Taken together, these results suggest that cordycepin inhibits the production of NO production by down-regulation of iNOS and COX-2 gene expression via the suppression of NF-κB activation, Akt and p38 phosphorylation. Thus, cordycepin may provide a potential therapeutic approach for inflammation-associated disorders.

AB - Cordyceps militaris, a caterpillar-grown traditional medicinal mushroom, produces an important bioactive compound, cordycepin (3′-deoxyadenosine). Cordycepin is reported to possess many pharmacological activities including immunological stimulating, anti-cancer, anti-virus and anti-infection activities. The molecular mechanisms of cordycepin on pharmacological and biochemical actions of macrophages in inflammation have not been clearly elucidated yet. In the present study, we tested the role of cordycepin on the anti-inflammation cascades in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. In LPS-activated macrophage, nitric oxide (NO) production was inhibited by butanol fraction of C. militaris and the major component of C. militaris butanol faction was identified as cordycepin by high performance liquid chromatography. To investigate the mechanism by which cordycepin inhibits NO production and inducible nitric oxide synthase (iNOS) expression, we examined the activation of Akt and MAP kinases in LPS-activated macrophage. Cordycepin markedly inhibited the phosphorylation of Akt and p38 in dose-dependent manners in LPS-activated macrophage. Moreover, cordycepin suppressed tumor necrosis factor (TNF-α) expression, IκB alpha phosphorylation, and translocation of nuclear factor-κB (NF-κB). The expressions of cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were significantly decreased in RAW 264.7 cell by cordycepin. Taken together, these results suggest that cordycepin inhibits the production of NO production by down-regulation of iNOS and COX-2 gene expression via the suppression of NF-κB activation, Akt and p38 phosphorylation. Thus, cordycepin may provide a potential therapeutic approach for inflammation-associated disorders.

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