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基于 UPLC-Q-TOF/MS 和网络药理学探讨清热利湿方治疗银屑病的作用机制。

Based on UPLC-Q-TOF/MS and Network Pharmacology to Explore the Mechanism of Qingre Lishi Decoction in the Treatment of Psoriasis.

机构信息

Department of Dermato-Venereology, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.

Department of Dermato-Venereology, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.

出版信息

Drug Des Devel Ther. 2024 Aug 28;18:3871-3889. doi: 10.2147/DDDT.S467066. eCollection 2024.

DOI:10.2147/DDDT.S467066
PMID:39219696
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11366256/
Abstract

BACKGROUND

Psoriasis is an immune-mediated chronic inflammatory disease. Qingre Lishi Decoction (QRLSD) has achieved great clinical effect in the treatment of psoriasis. However, the potential bioactive components and the mechanisms are yet unclear.

AIM

To analyze the serum parameters of rats fed with QRLSD, screen out the active components of QRLSD, and explore the potential targets and pathway of QRLSD in the treatment of psoriasis.

MATERIALS AND METHODS

The active components of serum containing QRLSD were analyzed using ultra-high performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS). The targets of QRLSD in the treatment of psoriasis were predicted by network pharmacology and molecular docking. In vitro experiments verified the underlying mechanism.

RESULTS

By UPLC-Q-TOF/MS, 15 prototype components and 22 metabolites were identified in serum containing QRLSD. Subsequently, 260 chemical composition targets and 218 psoriasis targets were overlapped to obtain 23 intersection targets, including LGALS3, TNF, F10, DPP4, EGFR, MAPK14, STAT3 and others. TNF, IL-10, GAPDH, STAT3, EGFR, ITGB1, LGALS3 genes were identified as potential drug targets in the PPI network analyzed by CytoHubba. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that QRLSD may improve psoriasis by regulating immune and inflammatory pathways, the cytokine mediated signal transduction pathways and other signaling pathways. Molecular docking results showed that the main active components of the serum containing QRLSD had higher affinities for TNF and LGALS3. In vitro experiments confirmed that QRLSD may decrease levels of inflammatory cytokines by suppressing the NF-κB signaling pathway activated by TNF-α in human keratinocytes.

CONCLUSION

This study explores the potential compounds, targets and signaling pathways of QRLSD in the treatment of psoriasis, which will help clarify the efficacy and mechanism of QRLSD.

摘要

背景

银屑病是一种免疫介导的慢性炎症性疾病。清热利湿汤(QRLSD)在治疗银屑病方面取得了显著的临床疗效。然而,其潜在的生物活性成分和作用机制尚不清楚。

目的

分析 QRLSD 含药血清的血清学参数,筛选 QRLSD 的活性成分,并探讨 QRLSD 治疗银屑病的潜在靶点和通路。

材料和方法

采用超高效液相色谱-四级杆飞行时间质谱联用技术(UPLC-Q-TOF/MS)分析 QRLSD 含药血清中的活性成分。通过网络药理学和分子对接预测 QRLSD 治疗银屑病的作用靶点。通过体外实验验证其潜在的作用机制。

结果

通过 UPLC-Q-TOF/MS 技术,鉴定出 QRLSD 含药血清中 15 个原型成分和 22 个代谢产物。随后,将 260 个化学成分靶点与 218 个银屑病靶点进行重叠,得到 23 个交集靶点,包括 LGALS3、TNF、F10、DPP4、EGFR、MAPK14、STAT3 等。通过 CytoHubba 分析 PPI 网络,确定 TNF、IL-10、GAPDH、STAT3、EGFR、ITGB1、LGALS3 等基因可能是潜在的药物靶点。GO 和 KEGG 分析表明,QRLSD 可能通过调节免疫和炎症通路、细胞因子介导的信号转导通路等信号通路改善银屑病。分子对接结果表明,QRLSD 含药血清中的主要活性成分与 TNF 和 LGALS3 具有较高的亲和力。体外实验证实,QRLSD 可能通过抑制 TNF-α激活的 NF-κB 信号通路降低人角质形成细胞中炎症细胞因子的水平。

结论

本研究探讨了 QRLSD 治疗银屑病的潜在化合物、靶点和信号通路,有助于阐明 QRLSD 的疗效和作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac6/11366256/a98636df6396/DDDT-18-3871-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac6/11366256/4d011e1697ad/DDDT-18-3871-g0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac6/11366256/e94a38167d09/DDDT-18-3871-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac6/11366256/d454e85881a9/DDDT-18-3871-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac6/11366256/a50a33c48fa5/DDDT-18-3871-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac6/11366256/5bc0f5a4595d/DDDT-18-3871-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac6/11366256/bebc39d1a9a5/DDDT-18-3871-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac6/11366256/a98636df6396/DDDT-18-3871-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac6/11366256/4d011e1697ad/DDDT-18-3871-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac6/11366256/18c75be63c76/DDDT-18-3871-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac6/11366256/ff4ca655a6fe/DDDT-18-3871-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac6/11366256/e94a38167d09/DDDT-18-3871-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac6/11366256/d454e85881a9/DDDT-18-3871-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac6/11366256/a50a33c48fa5/DDDT-18-3871-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac6/11366256/5bc0f5a4595d/DDDT-18-3871-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac6/11366256/bebc39d1a9a5/DDDT-18-3871-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac6/11366256/a98636df6396/DDDT-18-3871-g0009.jpg

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