Anti-psoriasis molecular targets and active components discovery of Optimized Yinxieling Formula via affinity-purified strategy

Psoriasis,a prevalent inherited skin condition,involves an inflammatory response as a key pathogenic mechanism.The Optimized Yinxieling Formula(OYF),rooted in traditional Chinese medicine,is extensively utilized in clinical settings to treat psoriasis.Although previous studies have demonstrated OYF’s significant anti-inflammatory effects in psoriasis,its potential molecular targets and active components remain unexplored.This study aimed to unveil the anti-psoriasis molecular targets and active components of OYF.Our findings indicated that OYF extract markedly reduced the production of several inflammatory mediators,including IL-23,nitric oxide,TNF-α,and IL-1β,in LPS-induced RAW264.7 cells.We synthesized OYF extract-crosslinked beads to isolate pharmacological targets from RAW264.7 lysates using an affinity purification strategy,known as Target Fishing.The enriched target proteins were subsequently identified via LC-MS/MS,followed by bioinformatics analysis to map the psoriasis-associated pathway-gene network.We identified a total of 76 potential target proteins,which were highly associated with mRNA transcription mechanisms.In particular,pathway-gene network analysis revealed that the IL-23 inflammatory pathway was involved in the anti-psoriasis effect of OYF extract.We further utilized a target protein-based affinity capture strategy,combined with LC-MS and SPR analysis,to globally screen OYF’s active components,focusing on the mRNA transcription regulator,fused in sarcoma(FUS).This process led to the identification of umbelliferone,vanillic acid,protocatechuic acid,gentisic acid,and echinacoside as key compounds targeting FUS to inhibit IL-23 expression.Additionally,we formulated a compound cocktail(CpdC),which significantly reduced psoriasis area and severity index(PASI)scores and the expressions of IL-23 and Ki67 in an imiquimod(IMQ)-induced psoriasis mouse model.Collectively,our study elucidates the primary molecular targets and active components of OYF,offering novel insights for psoriasis treatment.

A Randomized Controlled Single-Blind Clinical Trial on 84 Outpatients with Psoriasis Vulgaris by Auricular Therapy Combined with Optimized Yinxieling Formula(银屑灵优化方)

Objective：To explore the therapeutic effect of auricular therapy combined with optimized Yinxieling Formula（银屑灵优化方） on psoriasis vulgaris.Methods：A randomized controlled single-blind clinical trial on 84 outpatients with psoriasis vulgaris was conducted.The patients were randomized to a treatment group（43 cases treated by auricular therapy combined with optimized Yinxieling Formula） and a control group （41 cases treated by optimized Yinxieling Formula alone） according to a random number generated by SPSS 17.0 software.The treatment duration for both groups was 8 weeks.The therapeutic effect was comprehensively measured by the primary outcome measure[Psoriasis Area and Severity Index（PASI） reduction rate]and the secondary outcome measure[PASI,Visual Analogue Scale（VAS）,Dermatology Life Quality Index（DLQI）, Self-rating Depression Scale（SDS）,and Self-rating Anxiety Scale（SAS）].The outcomes of both groups were obtained and compared before and after the intervention.Results：The PASI reduction rate in the treatment group was 74.4%（32/43）,which was higher than that in the control group（36.6%,15/41,P0.01）.The PASI scores decreased in both groups after treatment and was lower in the treatment group compared with the control group （P0.01）.With stratified analysis,there were significant differences between the PASI scores in the following subgroups：age 18-30,baseline PASI10 and stable stage（P0.05）.DLQI decreased in both groups on some categories after treatment,but there were no significant differences between the two groups in SDS,SAS and VAS（P0.05）.No obvious adverse reactions were found in either group.Conclusion：The therapeutic effect of auricular therapy combined with Optimized Yinxieling Formula was superior to Optimized Yinxieling Formula alone with no obvious adverse reaction.