PT  - JOURNAL ARTICLE
AU  - Sachiko Koyama
AU  - Anna Purk
AU  - Manpreet Kaur
AU  - Helena A. Soini
AU  - Milos V. Novotny
AU  - Keith Davis
AU  - C. Cheng Kao
AU  - Hiroaki Matsunami
AU  - Anthony Mescher
TI  - Beta-caryophyllene enhances wound healing through multiple routes
AID  - 10.1101/611046
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 611046
4099  - http://biorxiv.org/content/early/2019/11/20/611046.short
4100  - http://biorxiv.org/content/early/2019/11/20/611046.full
AB  - 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.