Glycogen synthase kinase-3β (GSK3β) as a molecular target for cytokine-modulating effect of curcumin in a murine model of acute melioidosis infection

Anderson Tan, Nagesswary Ganesan, Suhaini Sudi, Sok Kuan Wong, Mohammed Noor Embi, Hasidah Mohd. Sidek

Research output: Contribution to journalArticle

Abstract

The present study was conducted to investigate the effect of curcumin treatment on survivability, cytokine response, and phosphorylation of glycogen synthase kinase-3β (GSK3β) in Burkholderia pseudomallei-infected mice. Curcumin, a bioactive compound identified in Curcuma longa has been reported to exhibit anti-inflammatory properties via inactivation of nuclear factor-kappa B (NF-κB) and consequent downregulation of pro-inflammatory cytokine production. Glycogen synthase kinase-3β (GSK3β) plays a pivotal role in the regulation of cytokine production. Here we used a murine model of acute melioidosis to investigate the effects of curcumin administration on experimental animal survivability, the phosphorylation state of GSK3β and levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-10 in serum, liver and spleen of B. pseudomallei-infected mice. Intraperitoneal administration of curcumin (60 mg/kg b.w.) significantly (P<0.05) improved survivability (44%) of infected mice compared to non-treated controls. Administration of curcumin resulted in elevated phosphorylation of Ser9 GSK3β (pGSK3β) levels in both liver and spleen of B. pseudomallei-infected mice (1.2-2.6 fold) compared to non-treated infected controls. In addition, curcumin treatment significantly (P<0.05) decreased (30% - 85%) the levels of pro-inflammatory cytokines (TNF-α and IFN-γ) in liver, spleen and serum of mice challenged with B. pseudomallei compared to non-treated infected controls. Increased levels (67%) of anti-inflammatory cytokine (IL-10) was also observed in serum of curcumin-treated infected mice. Our findings demonstrated that curcumin improved survivability of mice experimentally-infected with B. pseudomallei by modulating the pro- and anti-inflammatory cytokine response via inhibition of GSK3β.

Original languageEnglish
Pages (from-to)43-53
Number of pages11
JournalMalaysian Applied Biology
Volume46
Issue number4
Publication statusPublished - 1 Dec 2017

Fingerprint

Melioidosis
Glycogen Synthase Kinase 3
Curcumin
curcumin
Burkholderia pseudomallei
cytokines
animal models
Cytokines
Infection
mice
infection
phosphorylation
spleen
Anti-Inflammatory Agents
Spleen
tumor necrosis factors
Phosphorylation
interferons
interleukin-10
Interleukin-10

Keywords

  • Burkholderia pseudomallei
  • Curcumin
  • Glycogen synthase kinase-3β

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Glycogen synthase kinase-3β (GSK3β) as a molecular target for cytokine-modulating effect of curcumin in a murine model of acute melioidosis infection. / Tan, Anderson; Ganesan, Nagesswary; Sudi, Suhaini; Wong, Sok Kuan; Embi, Mohammed Noor; Mohd. Sidek, Hasidah.

In: Malaysian Applied Biology, Vol. 46, No. 4, 01.12.2017, p. 43-53.

Research output: Contribution to journalArticle

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abstract = "The present study was conducted to investigate the effect of curcumin treatment on survivability, cytokine response, and phosphorylation of glycogen synthase kinase-3β (GSK3β) in Burkholderia pseudomallei-infected mice. Curcumin, a bioactive compound identified in Curcuma longa has been reported to exhibit anti-inflammatory properties via inactivation of nuclear factor-kappa B (NF-κB) and consequent downregulation of pro-inflammatory cytokine production. Glycogen synthase kinase-3β (GSK3β) plays a pivotal role in the regulation of cytokine production. Here we used a murine model of acute melioidosis to investigate the effects of curcumin administration on experimental animal survivability, the phosphorylation state of GSK3β and levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-10 in serum, liver and spleen of B. pseudomallei-infected mice. Intraperitoneal administration of curcumin (60 mg/kg b.w.) significantly (P<0.05) improved survivability (44{\%}) of infected mice compared to non-treated controls. Administration of curcumin resulted in elevated phosphorylation of Ser9 GSK3β (pGSK3β) levels in both liver and spleen of B. pseudomallei-infected mice (1.2-2.6 fold) compared to non-treated infected controls. In addition, curcumin treatment significantly (P<0.05) decreased (30{\%} - 85{\%}) the levels of pro-inflammatory cytokines (TNF-α and IFN-γ) in liver, spleen and serum of mice challenged with B. pseudomallei compared to non-treated infected controls. Increased levels (67{\%}) of anti-inflammatory cytokine (IL-10) was also observed in serum of curcumin-treated infected mice. Our findings demonstrated that curcumin improved survivability of mice experimentally-infected with B. pseudomallei by modulating the pro- and anti-inflammatory cytokine response via inhibition of GSK3β.",
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