Naturally-occurring carnosic acid as a promising therapeutic agent for skin inflammation via targeting STAT1

Psoriasis and rosacea are prevalent chronic inflammatory skin disorders driven by aberrant interactions between skin-resident keratinocytes and immune cells. Natural products represent a largely untapped source of novel therapeutic agents for various diseases. This study aimed to identify an effective natural product for treating psoriasis and rosacea and to elucidate its underlying mechanism of action.

Bioinformatics and network pharmacology approaches were employed to identify potential drug candidates for these conditions. Psoriasis-like and rosacea-like inflammation models were established in mice to assess the in vivo therapeutic effects of carnosic acid. In vitro experiments were performed to investigate the molecular mechanisms underlying carnosic acid's anti-inflammatory activity.

Through bioinformatics and network pharmacology, carnosic acid, a plant-derived phenolic diterpene, was identified as a promising candidate for these skin disorders. Functional assays demonstrated that carnosic acid effectively inhibited skin inflammation in both imiquimod-induced psoriasis and LL37-induced rosacea mouse models. Mechanistically, carnosic acid bound directly to STAT1, inhibiting its phosphorylation and subsequent transcriptional activation, which led to a reduction in the production of STAT1-mediated inflammatory factors in keratinocytes. Topical application of carnosic acid significantly alleviated clinical symptoms in both psoriasis and rosacea models.

These findings suggest that carnosic acid holds potential as a therapeutic agent for STAT1-mediated skin inflammation.