Curcumin inhibits superoxide anion-induced pain-like behavior and leukocyte recruitment by increasing Nrf2 expression and reducing NF-κB activation

Inflamm Res. 2015 Dec;64(12):993-1003. doi: 10.1007/s00011-015-0885-y. Epub 2015 Oct 11.

Abstract

Objective: This study aimed at evaluating the activity of curcumin in superoxide anion-induced pain-like behavior and leukocyte recruitment in mice.

Treatment: Administration of curcumin 10 mg/kg subcutaneously 1 h before stimulus.

Methods: KO2 was used as superoxide anion donor. Overt pain-like behaviors were determined by the number of abdominal writhings, paw flinches and time spent licking the paw. Mechanical and thermal hyperalgesia were determined using an electronic anesthesiometer and hot plate, respectively. Cytokine concentration and NF-κB activity were determined by ELISA, antioxidant effect by nitrobluetretrazolium assay and ABTS radical scavenging ability. Myeloperoxidase activity was measured by colorimetric assay. The Nrf2, heme oxygenase-1 (HO-1) and gp91phox mRNA expression was determined by quantitative PCR. Data were analyzed by ANOVA followed by Tukey's post hoc and considered significant when p<0.05.

Results: Curcumin inhibited superoxide anion-induced overt pain-like behaviors as well as mechanical and thermal hyperalgesia. Curcumin also inhibited superoxide anion-induced leukocyte recruitment in the peritoneal cavity and in the paw skin inhibited myeloperoxidase activity, oxidative stress, IL-1β and TNF-α production and NF-κB activation as well as enhanced IL-10 production, and HO-1 and Nrf2 mRNA expression.

Conclusion: Curcumin inhibits superoxide anion-induced inflammatory pain-like behaviors and leukocyte recruitment by targeting inflammatory molecules and oxidative stress; and inducing antioxidant and anti-inflammatory pathways.

Keywords: Curcumin; IL-10; NF-κB; Nrf2; Pain; Superoxide anion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology*
  • Curcumin / administration & dosage
  • Curcumin / pharmacology*
  • Cytokines / biosynthesis
  • Heme Oxygenase-1 / biosynthesis
  • Hyperalgesia / chemically induced
  • Hyperalgesia / prevention & control
  • Injections, Subcutaneous
  • Leukocytes / drug effects*
  • Male
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Mice
  • NADPH Oxidase 2
  • NADPH Oxidases / biosynthesis
  • NADPH Oxidases / genetics
  • NF-E2-Related Factor 2 / biosynthesis*
  • NF-E2-Related Factor 2 / drug effects
  • NF-E2-Related Factor 2 / genetics
  • NF-kappa B / antagonists & inhibitors*
  • Oxidants / toxicity*
  • Oxidative Stress / drug effects
  • Oxides / chemistry
  • Pain / chemically induced
  • Pain / psychology*
  • Potassium Compounds / chemistry
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Superoxides / antagonists & inhibitors*
  • Superoxides / toxicity*

Substances

  • Antioxidants
  • Cytokines
  • Membrane Glycoproteins
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, mouse
  • Oxidants
  • Oxides
  • Potassium Compounds
  • RNA, Messenger
  • Superoxides
  • potassium oxide
  • Heme Oxygenase-1
  • Cybb protein, mouse
  • NADPH Oxidase 2
  • NADPH Oxidases
  • Curcumin