Therapeutic efficacy of Sanhuang Xiexin decoction on atopic dermatitis via suppressing STAT3 signaling.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Sanhuang Xiexin Decoction (SXD) is a traditional Chinese medicine formula widely used clinically for dermatitis due to its anti-inflammatory properties. However, the evidence for its therapeutic effect specifically in atopic dermatitis (AD) and the mechanisms underlying any such effects is lacking. AIM OF THE STUDY: To evaluate the efficacy of SXD on AD in mouse models and to elucidate the underlying mechanisms. MATERIALS AND METHODS: Network pharmacology was used to identify the active components of SXD and their potential therapeutic targets for AD. Binding affinities between the active ingredients and predicted targets were assessed with molecular docking and molecular dynamics simulations, followed by experimental verification using cellular thermal shift assay (CETSA). A DNCB-induced AD mouse model was established to evaluate the therapeutic efficacy of SXD. RNA sequencing and molecular biology techniques were employed to investigate the mechanisms by which SXD treats AD. RESULTS: Network pharmacology analysis identified 14 major pathways and 30 core targets in the SXD-targeted network. SXD appears to exert its therapeutic effects primarily by modulating key targets, especially signal transducer and activator of transcription 3 (STAT3). Binding assessments showed strong affinity between active SXD components and their targets. Further validation with molecular dynamics simulations and CETSA confirmed stable binding of epiberberine and baicalein to STAT3. In AD-model mice, SXD administration markedly reduced dermatitis symptoms, with effects comparable to dexamethasone (DEX) but without the weight loss observed in DEX-treated mice. SXD also lowered inflammatory cytokine expression. Western blot and immunohistochemistry validated the inhibition of STAT3 hyperactivation by SXD, and RNA sequencing of skin samples supported these findings. CONCLUSION: By modulating multiple pathways, especially the STAT3 signaling axis, SXD reduces skin inflammation in a mouse model of AD. Epiberberine, 5,7,4'-tri-hydroxy-8-methoxyflavone, baicalein, wogonin, and rivularin may contribute to SXD's therapeutic effects by targeting STAT3.