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

作     者：WANG Wei LIU Lijuan YANG Zhuo LU Chuanjian TU Pengfei ZHAO Ruizhi ZENG Kewu 

作者机构：State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Dampness Syndrome of Chinese MedicineThe Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510006China 

出 版 物：《Chinese Journal of Natural Medicines》 (中国天然药物（英文版）)

年 卷 期：2024年第22卷第2期

页      面：127-136页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 1002[医学-临床医学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by the State Key Laboratory of Dampness Syndrome of Chinese Medicine,the Second Affiliated Hospital of Guangzhou University of Chinese Medicine(No.SZ2021ZZ51) the National Key R&D Program of China(No.2022YFC3501601) the National Natural Sciences Foundation of China(Nos.82174008,81973505) Jinan New 20 Policies for Higher Education Funding(No.202228048)and the Fundamental Research Funds for the Central Universities 

主　　题：Psoriasis Optimized Yinxieling Formula(OYF) FUS protein Molecular targets Affinity-purified strategy 

摘      要：Psoriasis,a prevalent inherited skin condition,involves an inflammatory response as a key pathogenic *** Optimized Yinxieling Formula(OYF),rooted in traditional Chinese medicine,is extensively utilized in clinical settings to treat *** previous studies have demonstrated OYF’s significant anti-inflammatory effects in psoriasis,its potential molecular targets and active components remain *** study aimed to unveil the anti-psoriasis molecular targets and active components of *** 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 *** synthesized OYF extract-crosslinked beads to isolate pharmacological targets from RAW264.7 lysates using an affinity purification strategy,known as Target *** enriched target proteins were subsequently identified via LC-MS/MS,followed by bioinformatics analysis to map the psoriasis-associated pathway-gene *** identified a total of 76 potential target proteins,which were highly associated with mRNA transcription *** particular,pathway-gene network analysis revealed that the IL-23 inflammatory pathway was involved in the anti-psoriasis effect of OYF *** 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 ***,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 ***,our study elucidates the primary molecular targets and active components of OYF,offeri