Beta-caryophyllene enhances wound healing through multiple routes

PLoS One. 2019 Dec 16;14(12):e0216104. doi: 10.1371/journal.pone.0216104. eCollection 2019.

Abstract

Beta-caryophyllene is an odoriferous bicyclic sesquiterpene found in various herbs and spices. Recently, it was found that beta-caryophyllene is a ligand of the cannabinoid receptor 2 (CB2). Activation of CB2 will decrease pain, a major signal for inflammatory responses. We hypothesized that beta-caryophyllene can affect wound healing by decreasing inflammation. Here we show that cutaneous wounds of mice treated with beta-caryophyllene had enhanced re-epithelialization. The treated tissue showed increased cell proliferation and cells treated with beta-caryophyllene showed enhanced cell migration, suggesting that the higher re-epithelialization is due to enhanced cell proliferation and cell migration. The treated tissues also had up-regulated gene expression for hair follicle bulge stem cells. Olfactory receptors were not involved in the enhanced wound healing. Transient Receptor Potential channel genes were up-regulated in the injured skin exposed to beta-caryophyllene. Interestingly, there were sex differences in the impact of beta- caryophyllene as only the injured skin of female mice had enhanced re-epithelialization after exposure to beta-caryophyllene. Our study suggests that chemical compounds included in essential oils have the capability to improve wound healing, an effect generated by synergetic impacts of multiple pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Female
  • Hair Follicle / metabolism
  • Inflammation / drug therapy
  • Keratinocytes / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Polycyclic Sesquiterpenes / pharmacology*
  • Re-Epithelialization
  • Receptor, Cannabinoid, CB2 / drug effects*
  • Receptor, Cannabinoid, CB2 / genetics
  • Receptor, Cannabinoid, CB2 / metabolism
  • Sesquiterpenes / metabolism
  • Sex Factors
  • Skin / metabolism
  • Wound Healing / drug effects
  • Wound Healing / physiology*

Substances

  • Polycyclic Sesquiterpenes
  • Receptor, Cannabinoid, CB2
  • Sesquiterpenes
  • caryophyllene

Associated data

  • Dryad/10.5061/dryad.74421k0