Cinnamtannin B1 attenuates rosacea-like signs via inhibition of pro-inflammatory cytokine production and down-regulation of the MAPK pathway

Background. Rosacea is a common inflammatory disease of facial skin. Dysregulation of innate immunity with enhanced inflammation and increased abundance of LL-37 at the epidermal site is a characteristic feature of rosacea. Cinnamtannin B1 (CB1) is a condensed tannin with anti-inflammatory and anti-microbial activities. The aims of the study were to evaluate the potential of CB1 as a therapy for rosacea and to characterize the potential mechanisms of action. Methods. We intraperitoneally administered 20 mg/kg CB1 once daily for 2 days into the LL-37-induced mouse model of rosacea. The effects of CB1 in vivo were evaluated by the observations of lesions, histology, immunohistochemistry, and the transcription and translation of pro-inflammatory cytokines and chemokines. Human keratinocyte HaCaT and monocyte THP- 1 were used to characterize the effects of CB1 on LL-37-induced inflammation in vitro. The changes in pro-inflammatory chemokine interleukin-8 (IL-8) were quantitated by enzyme-linked immunosorbent assay (ELISA), and the expressions of genes involved were determined by Western blotting. Results. CB1 attenuated local redness, inflammation, and neutrophil recruitment in the mouse model of rosacea in vivo. CB1 suppressed myeloperoxidase (MPO) and macrophage inflammatory protein 2 (MIP-2) production, a functional homolog of interleukin-8 (IL-8), at the lesions. In vitro experiments confirmed that CB1 reversed the LL-37-induced IL-8 production in human keratinocytes HaCaT and monocyte THP-1 cells. CB1 inhibited IL-8 production through downregulating the phosphorylation of extracellular signal-regulated kinase (ERK) in the mitogen-activated protein kinase (MAPK) pathway. Conclusion. CB1 attenuated LL-37-induced inflammation, specifically IL-8 production, through inhibiting the phosphorylation of ERK. CB1 has potential as a treatment for rosacea.