The Antimalarial Effect of Curcumin Is Mediated by the Inhibition of Glycogen Synthase Kinase-3β

Amatul Hamizah Ali, Suhaini Sudi, Rusliza Basir, Mohammed Noor Embi, Hasidah Mohd. Sidek

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Curcumin, a bioactive compound in Curcuma longa, exhibits various pharmacological activities, including antimalarial effects. In silico docking simulation studies suggest that curcumin possesses glycogen synthase kinase-3β (GSK3β)-inhibitory properties. The involvement of GSK3 in the antimalarial effects in vivo is yet to be demonstrated. In this study, we aimed to evaluate whether the antimalarial effects of curcumin involve phosphorylation of host GSK3β. Intraperitoneal administration of curcumin into Plasmodium berghei NK65-infected mice resulted in dose-dependent chemosuppression of parasitemia development. At the highest dose tested (30 mg/kg body weight), both therapeutic and prophylactic administrations of curcumin resulted in suppression exceeding 50% and improved median survival time of infected mice compared to control. Western analysis revealed a 5.5-fold (therapeutic group) and 1.8-fold (prophylactic group) increase in phosphorylation of Ser 9 GSK3β and 1.6-fold (therapeutic group) and 1.7-fold (prophylactic group) increase in Ser 473 Akt in liver of curcumin-treated infected animals. Following P. berghei infection, levels of pro- and anti-inflammatory cytokines, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-10, and IL-4 were elevated by 7.5-, 35.0-, 33.0-, and 2.2-fold, respectively. Curcumin treatment (therapeutic) caused a significant decrease (by 6.0- and 2.0-fold, respectively) in serum TNF-α and IFN-γ level, while IL-10 and IL-4 were elevated (by 1.4- and 1.8-fold). Findings from the present study demonstrate for the first time that the antimalarial action of curcumin involved inhibition of GSK3β.

Original languageEnglish
Pages (from-to)152-161
Number of pages10
JournalJournal of Medicinal Food
Volume20
Issue number2
DOIs
Publication statusPublished - 1 Feb 2017

Fingerprint

Glycogen Synthase Kinase 3
Curcumin
Antimalarials
Plasmodium berghei
Interleukin-4
Interleukin-10
Interferons
Tumor Necrosis Factor-alpha
Phosphorylation
Curcuma
Parasitemia
Therapeutics
Computer Simulation
Malaria
Anti-Inflammatory Agents
Body Weight
Pharmacology
Cytokines
Liver

Keywords

  • curcumin
  • in vivo
  • inflammation
  • malaria
  • nuclear factor-kappa B (NF-κB)

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

The Antimalarial Effect of Curcumin Is Mediated by the Inhibition of Glycogen Synthase Kinase-3β. / Ali, Amatul Hamizah; Sudi, Suhaini; Basir, Rusliza; Embi, Mohammed Noor; Mohd. Sidek, Hasidah.

In: Journal of Medicinal Food, Vol. 20, No. 2, 01.02.2017, p. 152-161.

Research output: Contribution to journalArticle

Ali, Amatul Hamizah ; Sudi, Suhaini ; Basir, Rusliza ; Embi, Mohammed Noor ; Mohd. Sidek, Hasidah. / The Antimalarial Effect of Curcumin Is Mediated by the Inhibition of Glycogen Synthase Kinase-3β. In: Journal of Medicinal Food. 2017 ; Vol. 20, No. 2. pp. 152-161.
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