Wanjun Zhao , Xiaoyan Liu , Jianing Tang , Jieyu Chen , Dong Liu , Haiyan Sun , Jiao Qu , Yang Sun , Zijun Ouyang
{"title":"Jinkui Shenqi decoction targets PAD4 to restrain NETosis and ameliorates psoriasis progression","authors":"Wanjun Zhao , Xiaoyan Liu , Jianing Tang , Jieyu Chen , Dong Liu , Haiyan Sun , Jiao Qu , Yang Sun , Zijun Ouyang","doi":"10.1016/j.phymed.2025.156543","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>The underlying pathogenesis of psoriasis was attributed to insufficient kidney qi and blood stasis arising from impeded blood circulation. Jinkui Shenqi decoction (JKSQD), was renowned for its capacity to warm and tonify kidney yang, as well as to invigorate blood circulation. However, there remains a dearth of studies on its specific therapeutic effects and underlying mechanisms of psoriasis.</div></div><div><h3>Purpose</h3><div>Aiming to investigate the effectiveness and mechanism of JKSQD in the treatment of psoriasis.</div></div><div><h3>Methods</h3><div>Initially, we identified the compounds of JKSQD by UPLC-Q-TOF-MS/MS and constructed psoriasis-like mice to explore the effect of JKSQD on psoriasis. Subsequently, proteomic sequencing was conducted to identify key proteins and pathways involved in the therapeutic effect of JKSQD. Neutrophil extracellular traps (NETs) and peptidylarginine deiminase 4 (PAD4)-related indicators were detected to validate JKSQD mechanisms. At last, we analyzed metabolomic data to elucidate what metabolic pathway or metabolites worked during this procedure.</div></div><div><h3>Results</h3><div>We found that JKSQD effectively reversed the progression of psoriasis and associated inflammation in mice. Proteomic analysis further illuminated that PAD4 involved in NETosis was notably downregulated in psoriasis-like mice after JKSQD treatment. And a series of experiments further revealed that JKSQD inhibited NETs formation and PAD4 expression. Moreover, metabolomics demonstrated JKSQD influenced D-Arginine and D-ornithine metabolism, offering deeper insights into the mechanisms of JKSQD on psoriasis.</div></div><div><h3>Conclusions</h3><div>This study unveiled that JKSQD could improve psoriasis progression by targeting PAD4 to inhibit NETs formation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156543"},"PeriodicalIF":6.7000,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Phytomedicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0944711325001849","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background
The underlying pathogenesis of psoriasis was attributed to insufficient kidney qi and blood stasis arising from impeded blood circulation. Jinkui Shenqi decoction (JKSQD), was renowned for its capacity to warm and tonify kidney yang, as well as to invigorate blood circulation. However, there remains a dearth of studies on its specific therapeutic effects and underlying mechanisms of psoriasis.
Purpose
Aiming to investigate the effectiveness and mechanism of JKSQD in the treatment of psoriasis.
Methods
Initially, we identified the compounds of JKSQD by UPLC-Q-TOF-MS/MS and constructed psoriasis-like mice to explore the effect of JKSQD on psoriasis. Subsequently, proteomic sequencing was conducted to identify key proteins and pathways involved in the therapeutic effect of JKSQD. Neutrophil extracellular traps (NETs) and peptidylarginine deiminase 4 (PAD4)-related indicators were detected to validate JKSQD mechanisms. At last, we analyzed metabolomic data to elucidate what metabolic pathway or metabolites worked during this procedure.
Results
We found that JKSQD effectively reversed the progression of psoriasis and associated inflammation in mice. Proteomic analysis further illuminated that PAD4 involved in NETosis was notably downregulated in psoriasis-like mice after JKSQD treatment. And a series of experiments further revealed that JKSQD inhibited NETs formation and PAD4 expression. Moreover, metabolomics demonstrated JKSQD influenced D-Arginine and D-ornithine metabolism, offering deeper insights into the mechanisms of JKSQD on psoriasis.
Conclusions
This study unveiled that JKSQD could improve psoriasis progression by targeting PAD4 to inhibit NETs formation.
期刊介绍:
Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.