The elucidation of the anti-inflammatory mechanism of EMO in rheumatoid arthritis through an integrative approach combining bioinformatics and experimental verification

作者全名："Hui, Pusheng; Zhou, Sicong; Cao, Chunhao; Zhao, Wenting; Zeng, Li; Rong, Xiaofeng"

作者地址："[Hui, Pusheng; Zhou, Sicong; Cao, Chunhao; Zeng, Li; Rong, Xiaofeng] Chongqing Med Univ, Dept Integrated Tradit Chinese & Western Med, Affiliate Hosp 1, Chongqing, Peoples R China; [Zhao, Wenting] Hubei Univ Chinese Med, Clin Coll 1, Wuhan, Peoples R China"

通信作者："Zeng, L; Rong, XF (通讯作者)，Chongqing Med Univ, Dept Integrated Tradit Chinese & Western Med, Affiliate Hosp 1, Chongqing, Peoples R China."

来源：FRONTIERS IN PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001010586100001

JCR分区：Q1

影响因子：4.4

年份：2023

卷号：14

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Emodin; rheumatoid arthritis; RNA-seq; single cell RNA-seq; inflammatory

摘要："Introduction: Emodin (EMO), a natural derivative of the anthraquinone family mainly extracted from rhubarb (Rheum palmatum), has previously been demonstrated to possess superior anti-inflammatory properties from a single target or pathway. In order to explore the underlying mechanism of action of EMO against rheumatoid arthritis (RA), a network pharmacology approach was employed. Methods: A gene expression profile from GSE55457 available from the Gene Expression Omnibus (GEO) database was used to identify the targets of EMO action. Further, single cell RNA sequencing data from GEO database of RA patients (GSE159117) were downloaded and analysed. To further investigate the anti-RA effect of EMO on MH7A cells, the expression of IL-6 and IL-1 ss were monitored. Finally, RNA-seq analyses were conducted on synovial fibroblasts from EMOtreated. Result: We screened the key targets of EMO against RA using network pharmacology methods, including HMGB1, STAT1, EGR1, NR3C1, EGFR, MAPK14, CASP3, CASP1, IL4, IL13, IKBKB and FN1, and their reliability was verified using ROC curve. Single-cell RNA sequencing data analysis showed that these core target proteins mainly played a role by modulating monocytes. The anti-RA effect of EMO was further verified with MH7A cells, which showed that EMO could block cell differentiation and reduce the expression of IL-6 and IL-1 ss. WB experiments confirmed that EMO could affect the expression of COX2, HMBG1 and the phosphorylation of p38. Finally, sequencing of synovial fibroblasts from rats treated with EMO showed consistent results with those predicted and verified, further proving the anti-inflammatory effect of EMO. Conclusion: Our research shows that EMO inhibits inflammatory response of rheumatoid arthritis (RA) by targeting HMGB1, STAT1, EGR1, NR3C1, EGFR, MAPK14, CASP3, CASP1, IL4, IL13, IKBKB, FN1 and Monocytes/macrophages."

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