Written by Joyce Smith, BS. Study suggests that beta-caryophyllene, a chemical compound found in essential oils, has the ability along with the synergistic impact of multiple pathways to improve wound healing.

essential oilBeta-caryophyllene is an odoriferous bicyclic sesquiterpene found in the essential oils of various herbs such as lavender, rosemary, and ylang ylang, as well as in spices such as black pepper. It has been used to reduce stress and pain, and to promote recovery from injury or illness 1.  Essential oils can vary greatly in their strength and purity due to extraction methods 2, geographical areas of origin 3, seasons when harvested 4 and parts of the plants that are abstracted 5, thus chemically pure compounds are paramount in research 6. BCP has recently been found to be a ligand of the cannabinoid receptor 2 (CB2) 7. Activation of CB2 will decrease pain, a major signal for inflammatory responses and has also been shown to improve re-epithelialization in wound healing. Although Essential oil of Copaifera pauper, which contains BCP, also improves wound healing 8, it remains unclear whether BCP plays a direct role and whether the CB2 receptor promotes the wound healing. Koyama and team 9 sought to determine whether BCP can improve wound re- epithelialization and, if so, whether the olfactory system contributes to the process.

Cutaneous wounds of mice were treated with a topical application of BCP diluted with olive oil (BCP group) or with olive oil alone (control group) and examined for cell proliferation and migration, and potential changes in gene expression. Koyama and colleagues also compared the impact of BCP on wound healing in male and female mice and determined whether olfactory receptors were involved in wound healing. The following observations were made:

  • The cutaneous wounds of mice treated with a topical application of BCP demonstrated significantly enhanced re-epithelialization enhanced cell proliferation; and enhanced cell migration compared to the cutaneous wounds of mice treated with olive oil alone 10 (p<0.05).
  • RNA sequencing and transcriptome analyses revealed significant differences in gene expression between the BCP group and Oil treated group.
  • BCP treatment significantly up-regulated a large number of genes. Forty of the top 50 of these up-regulated genes were coded for cell migration, cell fate determination, and hair follicle formation, suggesting that BCP stimulates hair follicle stem cell proliferation, and skin regeneration to improve wound healing.
  • There were no significant differences in re-epithelialization when comparing the BCP and Oil treated male mice or when comparing wound healing in BCP-treated male and female mice.
  • Olfactory receptors were not involved in wound healing

Beta-caryophyllene activates not only olfactory receptors but also CB2, which exhibits an anti-inflammatory impact when it is activated. Koyama et al demonstrated that there are several stages in the wound healing process: the inflammatory phase followed by a cell proliferation stage and the remodeling stage. The anti-inflammatory effect of BCP’s activation of CB2 accelerated the wound healing process by stimulating an earlier switch from the inflammatory stage of healing to the next stage. The resulting change in gene expression validates that improved healing involves not only the activation of the CB2 receptor but more pathways that act synergistically. While this study focused on the early stages of wound healing, the authors recommend future studies that explore BCPs influence on the later stages of wound healing including scar formation.

Source: Koyama, Sachiko, Anna Purk, Manpreet Kaur, Helena A. Soini, Milos V. Novotny, Keith Davis, C. Cheng Kao, Hiroaki Matsunami, and Anthony Mescher. “Beta-caryophyllene enhances wound healing through multiple routes.” PloS one 14, no. 12 (2019).

© 2019 Koyama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Posted January 13, 2020.

Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from  the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.

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