Presentation Details
Beta-caryophyllene improves cutaneous wound healing in mice through multiple mechanisms

Sachiko Koyama1, Anna Purk1, Manpreet Kaur1, Helena Soini1, Milos Novotny1, Keith Davis1, Cheng Kao1, Hiroaki Matsunami2, Anthony Mescher1.

1Indiana University, Bloomington, IN, USA.2Duke University, Durham, NC, USA

Abstract


We have a long history of actively utilizing odorants to heal or alter our physiological conditions. A variety of herbal plants’ extracts have been used to reduce stress and pain, and to promote recovery from injury or illness. Despite this long history of using herbal plant extracts, there is still a strong need of scientific evidences regarding the effects of such extracts. Beta-caryophyllene (BCP) is an odoriferous bicyclic sesquiterpene found in various herbs and spices. It has odor (activates olfactory system) and it is a ligand of cannabinoid receptor 2 (CB2). As activation of CB2 is known to have anti-inflammatory impacts, we hypothesized that BCP may affect wound healing by decreasing inflammation. Here we show that cutaneous wounds in mice treated topically with BCP enhanced re-epithelialization and increased cell proliferation. Primary cell cultures treated with BCP showed enhanced cell migration. These results suggested that the greater re-epithelialization is due to both enhanced cell proliferation and cell migration. When primary cell cultures from CB2 knockout mice were exposed to BCP, they did not show enhanced migration in chemotaxis assays, implicating this pathway, but there were no migratory differences in scratch tests suggesting involvement of other routes as well. RNA sequencing revealed large differences in gene expression between injured, BCP-treated skin and controls. Genes related to embryonic growth as well as hair follicle stem cells were up-regulated in BCP-treated tissue. Transient Receptor Potential channel genes were up-regulated in the injured skin exposed to BCP, indicating their possible involvement in the improved re-epithelialization. Our study suggests that BCP has the capacity to improve wound healing through multiple pathways.  

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