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

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Chinese Journal of Natural Medicines 2024年第2期22卷 127-136页

作者： WANG Wei LIU Lijuan YANG Zhuo LU Chuanjian TU Pengfei ZHAO Ruizhi ZENG Kewu State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Dampness Syndrome of Chinese Medicine The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510006China

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

关键词： Psoriasis Optimized Yinxieling Formula(OYF) fus protein Molecular targets Affinity-purified strategy

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