Chelerythrine alleviates inflammation and angiogenesis in a mouse rosacea model via suppressing the NF-κB/p38 MAPK/STAT3 pathways.

Abstract

Rosacea is a chronic inflammatory skin condition marked by excessive M1 macrophage polarization and angiogenesis, resulting in erythema and tissue inflammation. Despite available treatments, many patients experience recurrent flare-ups. This study explores chelerythrine, a bioactive component ofCortex, for its therapeutic potential in rosacea through modulation of NF-κB, p38 MAPK, and STAT3 signaling, inflammation, and vascular regulation. Using an LL-37-induced rosacea-like mouse model, THP-1-derived M1 macrophages and human umbilical vein endothelial cells (HUVECs), chelerythrine's effects on macrophage polarization, cytokine expression, angiogenesis, and pathway activation of NF-κB, p38 MAPK, and STAT3 were evaluated. Chelerythrine significantly reduced epidermal thickness, inflammatory cell infiltration, and pro-inflammatory markers (TNF-α and IL-1β). It inhibited NF-κB, p38 MAPK, and STAT3 activation and decreased M1 polarization markers, shifting towards an anti-inflammatory profile. Furthermore, chelerythrine reduced vascular density and VEGF expression, impairing angiogenesis-related behaviors in HUVECs. These findings suggest that chelerythrine holds promise as a treatment for rosacea by mitigating inflammation and angiogenesis through targeted multiple pathways and macrophage modulation.