Wogonin

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.

To evaluate the efficacy of SXD on AD in mouse models and to elucidate the underlying mechanisms.

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.

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.

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.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia and multi-organ damage. While existing therapies alleviate symptoms, they are accompanied by significant adverse effects. Fibroblast-like synoviocytes (FLS) drive RA progression through inflammation-coagulation interactions, necessitating safer multitarget drugs. Jianpi Wenyang Tongluo Prescription-Wuwei Wentong Chubi Capsule (WWT), a traditional Chinese medicine formula targeting the "cold-dampness obstruction syndrome" in RA, has demonstrated clinical efficacy, yet its mechanism remains unclear.

To investigate the therapeutic effects of WWT on adjuvant-induced arthritis (AA) rats with cold-dampness syndrome and explore its underlying mechanisms in regulating inflammation-coagulation balance and organ protection.

AA rats with cold-dampness syndrome were established using Freund's complete adjuvant (FCA) and a climate chamber, and treated with WWT (low/medium/high doses). Synovial pathology, organ function, inflammatory, and coagulation parameters were evaluated. Molecular docking, protein-protein interaction (PPI) networks, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were employed to identify key targets, with Western blot (WB) and immunofluorescence used to validate JAK2/STAT3 pathway activation. A coculture model of peripheral blood mononuclear cells (PBMCs) and FLS from RA patients was constructed for in vitro validation.

In AA rats, WWT dose-dependently decreased pro-inflammatory cytokines (IL-6, IL-17) and pro-coagulant factors (PAF, FDP), while increasing anti-inflammatory cytokine IL-10 and anticoagulant factor PGI2 (P < 0.01). WWT reversed synovial mitochondrial vacuolation and protected liver and kidney function. Bioinformatics analysis and molecular docking revealed JAK2/STAT3 as the core target, with wogonin and icariin stably binding to JAK2 (ΔG = -8.2/-7.7 kcal/mol) and STAT3 (ΔG = -7.9/-9.9 kcal/mol). WWT rescued inflammation and hypercoagulation induced by the JAK2/STAT3 activator coumermycin A1. In vitro, WWT-containing serum inhibited the proliferation of cocultured RA-PBMCs and FLS and the secretion of pro-inflammatory and pro-coagulant factors by blocking JAK2/STAT3 and STAT3 nuclear translocation.

WWT alleviates RA progression by restoring inflammation-coagulation balance and protecting multi-organ function through inhibition of the JAK2/STAT3 pathway. This study integrates traditional Chinese medicine theory with molecular pathological mechanisms, providing a scientific basis for WWT as a multitarget therapeutic for RA.