Thymol activates TRPM8-mediated Ca2+ influx for its antipruritic effects and alleviates inflammatory response in Imiquimod-induced mice

Toxicol Appl Pharmacol. 2020 Nov 15:407:115247. doi: 10.1016/j.taap.2020.115247. Epub 2020 Sep 22.

Abstract

Psoriasis is a highly prevalent chronic dermatitis, characterized by widespread skin inflammation and spontaneous itch. Given the adverse reactions and drug dependence of current treatment, new drugs for psoriasis therapy are urgently needed. This study aims to explore the anti-psoriatic effects of thymol in imiquimod (IMQ) induced mice, and elucidate the potential mechanisms for its therapeutic activities. Thymol reduced the scratching behavior in IMQ mice, and activated Ca2+ response in cervical DRG neurons via TRPM8 channel. Also, thymol alleviated psoriasis-like skin lesions, and attenuated the enhanced infiltration of dermal neutrophils, dendritic cells (DCs) and Th17 cells. In addition, it reversed the upregulated expression of pro-inflammatory cytokines in the skin (TNF-α, IL-22, IL-23, IL-17A, IL-17F, IL-17C, IL-6, IL-1β and IFN-γ) and serum (TNF-α, IL-6, IL-1β, IL-17A and IFN-γ). Our results indicated that thymol can effectively ameliorate pruritus and the symptoms of psoriasis-like inflammation induced by IMQ, which makes it a promising drug for the treatment of psoriasis.

Keywords: Inflammation; Pruritus; Psoriasis; TRPM8; Thymol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipruritics / pharmacology*
  • Behavior, Animal
  • Calcium / metabolism*
  • Cell Differentiation / drug effects
  • Cytokines / blood
  • Cytokines / metabolism
  • Imiquimod*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neurons / drug effects
  • Pruritus / chemically induced
  • Pruritus / prevention & control
  • Pruritus / psychology
  • Psoriasis / chemically induced
  • Psoriasis / drug therapy*
  • Skin / drug effects
  • Skin / metabolism
  • TRPM Cation Channels / agonists*
  • Thymol / pharmacology*

Substances

  • Antipruritics
  • Cytokines
  • TRPM Cation Channels
  • TRPM8 protein, mouse
  • Thymol
  • Imiquimod
  • Calcium