Jinkui Shenqi decoction targets PAD4 to restrain NETosis and ameliorates psoriasis progression

IF 8.3 1区 医学 Q1 CHEMISTRY, MEDICINAL Phytomedicine Pub Date : 2025-04-01 Epub Date: 2025-02-19 DOI:10.1016/j.phymed.2025.156543
Wanjun Zhao , Xiaoyan Liu , Jianing Tang , Jieyu Chen , Dong Liu , Haiyan Sun , Jiao Qu , Yang Sun , Zijun Ouyang
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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.

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金葵参芪汤以PAD4为靶点抑制NETosis,改善银屑病进展
背景银屑病的根本病机是肾气不足、血瘀成风。金葵参气汤(JKSQD),以其温补肾阳,活血循环的能力而闻名。然而,关于其治疗银屑病的特异性效果和潜在机制的研究仍然缺乏。目的:探讨散散方治疗银屑病的疗效及作用机制。方法采用UPLC-Q-TOF-MS/MS法鉴定其化合物,构建牛皮癣样小鼠,探讨其对牛皮癣的治疗作用。随后,进行蛋白质组学测序以确定参与JKSQD治疗效果的关键蛋白和途径。检测中性粒细胞胞外陷阱(NETs)和肽精氨酸脱亚胺酶4 (PAD4)相关指标来验证JKSQD的机制。最后,我们分析了代谢组学数据来阐明代谢途径或代谢物在这一过程中起作用。结果我们发现JKSQD有效地逆转了小鼠牛皮癣和相关炎症的进展。蛋白质组学分析进一步表明,JKSQD治疗后,银屑病样小鼠中参与NETosis的PAD4显著下调。一系列实验进一步揭示JKSQD抑制NETs的形成和PAD4的表达。此外,代谢组学研究表明,JKSQD影响d -精氨酸和d -鸟氨酸的代谢,为JKSQD治疗银屑病的机制提供了更深入的见解。结论JKSQD可能通过靶向PAD4抑制NETs的形成而改善银屑病的进展。
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来源期刊
Phytomedicine
Phytomedicine 医学-药学
CiteScore
10.30
自引率
5.10%
发文量
670
审稿时长
91 days
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.
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