In vivo and in vitro investigation of skin anti-inflammatory effect of Sumac (Rhus coriaria L.)

Background: Sumac (Rhus coriaria L., Anacardiaceae) fruit is receiving a growing attention as potential nutraceutical and cosmetic ingredient. It is appreciated either as a spice and medicinal remedy in Middle East countries. The application of fruits preparations to skin injuries emerged from ethnopharmacological studies, sustained by few experimental studies on wound healing. The present work, based on previous evidence of in vitro anti-inflammatory activity in human keratinocytes (HaCaT), is aimed at translating the in vitro effect of sumac to an in vivo model of dermatitis. Results: Two polar sumac fruit extracts (acetone extract, ARC; ethanol extracts, mERC) were investigated in mice by Croton oil-induced ear dermatitis model. The in vivo topical anti-inflammatory activity was investigated 6 h and 24 h after dermatitis induction by means of edema, leukocyte infiltrate, and histological features; the expression of inflammatory genes was also analyzed by PCR array. Biological targets identified in vivo were validated in vitro by stimulating HaCaT cells with pro-inflammatory mediators for the same exposure time-points (6 h and 24 h). Both the extracts inhibited PMA-induced IL8 release in HaCaT cells, but mERC showed lower IC50 (18.68 μg/mL vs. 26.34 μg/mL, respectively). According to the in vitro effect, both the extracts (300–1000 µg/mL) reduced edema and neutrophilic granulocytes infiltrate in mice auricle at 6 h and 24 h after dermatitis induction, with comparable activity. The gene expression profile in the inflamed ear tissues suggested the involvement of TNF and IL4/IL13 pathways in ARC and mERC anti-inflammatory activity. This hypothesis was confirmed by further in vitro experiments on HaCaT cells, in which both extracts impaired TNF-induced IL-8 with IC50 below 1.5 μg/mL. Once, again mERC showed slightly lower IC50 then ARC (1.32 μg/mL vs. 1.63 μg/mL). In analogy, the most promising extract also impaired the release of IL-4-induced CCL26, with IC50 of 1.06 µg/mL. Conclusions: This study supports the relevance of the biological properties of sumac fruit for skin inflammation. Moreover, mechanisms of action related to TNF and IL4/IL13 pathways suggest further specific investigations related to skin allergy and autoimmune diseases.