Isosilybin A exhibits anti-inflammatory properties in rosacea by inhibiting MAPK pathway and M1 macrophage polarization

Rosacea is a chronic inflammatory skin disease, which is prone to flares and requires continuous management and treatment. However, long-term use of drugs can lead to additional adverse drug reactions. Based on the comorbid relationship between rosacea and Parkinson's disease, bioinformatics and network pharmacology analysis were used to identify a safer drug for rosacea. It has been demonstrated that ISA has an ameliorative impact on the symptoms of Parkinson's disease. The results demonstrated that ISA exhibited anti-inflammatory properties, including reducing erythema areas and inflammatory cell infiltration in rosacea-like mice models, and inhibiting the expression of inflammatory factors in cellular inflammation models. Furthermore, the anti-inflammatory effect of ISA was associated with inhibition of the Erk, p38 and NF-κB signaling pathways and inhibition of macrophage polarization to M1 type. In addition, molecular docking and drug affinity responsive target stability experiment results indicated that VEGFA and RELA were the direct targets of ISA in the treatment for rosacea. In conclusion, these results suggested that ISA may be a potential therapeutic agent for rosacea.