Abstract

Rosacea is a chronic inflammatory skin disorder that significantly impairs patients’ quality of life. However, current treatment options remain inadequate. Tanshinone IIA, a bioactive compound derived from the herb Danshen, is known for its anti-inflammatory properties. Based on tanshinone IIA, a novel drug, TA20, was developed. This study aims to evaluate the therapeutic effects of TA20 and elucidate its underlying molecular mechanisms in the treatment of rosacea. The rosacea mouse model was established using LL37, and keratinocyte inflammation was induced in vitro using TNF-α. The therapeutic effects of TA20 on rosacea-related molecular pathological changes were assessed through histological examination (HE staining), RNA sequencing, immunohistochemistry, immunofluorescence, Western blotting, and quantitative real-time PCR. TA20 effectively alleviated rosacea symptoms in the mouse model. RNA sequencing revealed that TA20 reduced inflammation primarily by modulating immune and inflammatory responses. Both in vivo and in vitro experiments demonstrated that TA20 suppressed the expression of rosacea-associated cytokines and chemokines, as well as reduced the infiltration of CD4+ T cells. Further analysis showed that TA20 treatment was associated with decreased IL6 production and reduced STAT3 phosphorylation in keratinocytes. These findings suggest that TA20, a tanshinone derivative, ameliorates rosacea-like skin inflammation and is accompanied by attenuation of IL6/STAT3 signaling in keratinocytes. TA20 holds promise as a potential therapeutic option for the treatment of rosacea.