Objective:Angelica(A.)sinensis is used as a traditional medical herb for the treatment of neurodegeneration,aging,and inflammation in Asia.A.sinensis optimal formula(AOF)is the best combination in A.sinensis that has ...Objective:Angelica(A.)sinensis is used as a traditional medical herb for the treatment of neurodegeneration,aging,and inflammation in Asia.A.sinensis optimal formula(AOF)is the best combination in A.sinensis that has been screened to rescue the cognitive ability in P-amyloid peptide(Ap25-35)-treated Alzheimer’s disease(AD)rats.The objective of this study was to investigate the effect of AOF on the learning and memory of AD rats as well as to explore the underlying mechanisms.展开更多
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 cl...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.展开更多
基金This project was supported by the National Natural Science Foundation of China(No.81960828).
文摘Objective:Angelica(A.)sinensis is used as a traditional medical herb for the treatment of neurodegeneration,aging,and inflammation in Asia.A.sinensis optimal formula(AOF)is the best combination in A.sinensis that has been screened to rescue the cognitive ability in P-amyloid peptide(Ap25-35)-treated Alzheimer’s disease(AD)rats.The objective of this study was to investigate the effect of AOF on the learning and memory of AD rats as well as to explore the underlying mechanisms.
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)+1 种基金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.
文摘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.