Beta‐caryophyllene as an antioxidant, anti‐inflammatory and re‐epithelialization activities in a rat skin wound excision model

Abstract

The skin is a critical organ for the maintenance of the integrity and protection of the organism. When a wound occurs, a sequence of healing mechanisms is triggered to reconstruct the wounded area. <i>β</i>-caryophyllene is a sesquiterpene in <i>Copaifera langsdorffii</i> oleoresin with antioxidant and anti-inflammatory potential. On the basis of previous studies with <i>C. langsdorffii</i>, <i>β</i>-caryophyllene was selected to evaluate its wound healing potential and pharmacological mechanisms. The excision wound model was used with male <i>Wistar</i> rats and macroscopic, histological, immunohistochemical and biochemical analyses were performed with skin samples, comparing the <i>β</i>-caryophyllene-treated group with reference drugs. The results showed macroscopic retraction of the wounds treated with <i>β</i>-caryophyllene. Biochemical assays revealed the antioxidant and anti-inflammatory mechanisms of the <i>β</i>-caryophyllene-treated group with increasing levels of IL-10 and GPx and decreasing levels of pro-inflammatory molecules, including TNF-<i>α</i>, IFN-<i>γ</i>, IL-1<i>β</i> and IL-6. After <i>β</i>-caryophyllene treatment, immunohistochemical assays showed enhanced re-epithelialization, through the increase in laminin-<i>γ</i>2 and desmoglein-3 immunolabeling. <i>β</i>-caryophyllene also act in the remodeling mechanism, increasing the collagen content in the Masson's trichrome staining. These findings indicated the wound-healing potential of <i>β</i>-caryophyllene topical formulation in rat skin wounds, mediated by antioxidant, anti-inflammatory and re-epithelialization mechanisms.