Vitexin inhibits inflammatory pain in mice by targeting TRPV1, oxidative stress, and cytokines

J Nat Prod. 2013 Jun 28;76(6):1141-9. doi: 10.1021/np400222v. Epub 2013 Jun 6.

Abstract

The flavonoid vitexin (1) is a flavone C-glycoside (apigenin-8-C-β-D-glucopyranoside) present in several medicinal and other plants. Plant extracts containing 1 are reported to possess antinociceptive, anti-inflammatory, and antioxidant activities. However, the only evidence that 1 exhibits antinociceptive activity was demonstrated in the acetic acid-induced writhing model. Therefore, the analgesic effects and mechanisms of 1 were evaluated. In the present investigation, intraperitoneal treatment with 1 dose-dependently inhibited acetic acid-induced writhing. Furthermore, treatment with 1 also inhibited pain-like behavior induced by phenyl-p-benzoquinone, complete Freund's adjuvant (CFA), capsaicin (an agonist of transient receptor potential vanilloid 1, TRPV1), and both phases of the formalin test. It was also observed that inhibition of carrageenan-, capsaicin-, and chronic CFA-induced mechanical and thermal hyperalgesia occurred. Regarding the antinociceptive mechanisms of 1, it prevented the decrease of reduced glutathione levels, ferric-reducing ability potential, and free-radical scavenger ability, inhibited the production of hyperalgesic cytokines such as TNF-α, IL-1β, IL-6, and IL-33, and up-regulated the levels of the anti-hyperalgesic cytokine IL-10. These results demonstrate that 1 exhibits an analgesic effect in a variety of inflammatory pain models by targeting TRPV1 and oxidative stress and by modulating cytokine production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Apigenin / pharmacology*
  • Apigenin / therapeutic use
  • Benzoquinones
  • Capsaicin / adverse effects
  • Capsaicin / therapeutic use
  • Carrageenan / adverse effects
  • Carrageenan / therapeutic use
  • Cytokines / adverse effects
  • Cytokines / biosynthesis
  • Cytokines / therapeutic use
  • Disease Models, Animal
  • Freund's Adjuvant / pharmacology
  • Glycosides / adverse effects
  • Glycosides / therapeutic use
  • Hyperalgesia / drug therapy
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Male
  • Mice
  • Molecular Structure
  • Oxidative Stress / drug effects
  • Pain / chemically induced
  • Pain / drug therapy
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • TRPV Cation Channels / drug effects*

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Benzoquinones
  • Cytokines
  • Glycosides
  • Plant Extracts
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • apigenin-8-C-beta-D-glucopyranoside
  • phenylbenzoquinone
  • Apigenin
  • Carrageenan
  • Freund's Adjuvant
  • vitexin
  • Capsaicin