A network pharmacology approach to investigate the anti-inflammatory mechanism of effective ingredients from Salvia miltiorrhiza

被引：36

作者：

Cui, Shuna ^{[1
,2
,3
]}

Chen, Shanshan ^{[1
]}

Wu, Qingqing ^{[1
]}

Chen, Tingting ^{[1
]}

Li, Shihua ^{[2
]}

机构：

[1] Yangzhou Univ, Jiangsu Key Lab Integrated Tradit Chinese & Weste, Med Coll, JiangYang Middle Rd 136, Yangzhou 225001, Jiangsu, Peoples R China

[2] Yangzhou Univ, Dept Obstet & Gynecol, Affiliated Hosp, Yangzhou, Jiangsu, Peoples R China

[3] Coll Vet Med, Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou, Jiangsu, Peoples R China

来源：

INTERNATIONAL IMMUNOPHARMACOLOGY | 2020年 / 81卷

基金：

中国国家自然科学基金;

关键词：

Network pharmacology; Tanshinone I; Cryptotanshinone; Inflammation; COMPARATIVE TOXICOGENOMICS DATABASE; TANSHINONE IIA; INFLAMMATION; MACROPHAGES; EXPRESSION; GENECARDS; RESOURCE; DISEASE; GENES; MODEL;

D O I：

10.1016/j.intimp.2019.106040

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Salvia miltiorrhiza, known as Danshen in Chinese, has been widely used to treat cardiovascular diseases in China. Tanshinone I (Tan I) and cryptotanshinone (CST) are the lipid-soluble and effective components from Salvia miltiorrhiza. However, the molecular mechanism of Tan I and CST for treating inflammation is still not known. Therefore, this study was designed to use network pharmacology-based strategy to predict therapeutic targets of Tan I and CST against inflammation, and further to investigate the pharmacological molecular mechanism in vitro. Inflammation targets were identified and followed by acquisition of verified targets of Tan I and CST. After constructing target-functional protein interaction network of Tan I and CST against inflammation, the core therapeutic targets of Tan I and CST against inflammation were obtained. Further, pathway enrichment analyses were performed on core therapeutic targets to evaluate key signaling pathways of Tan I and CST against inflammation. As revealed in network pharmacology analysis, 8 key hub targets for Tan I and CST against inflammation were identified, respectively: JUN, VEGFA, IL-6, TNF, MAPK8, CXCL8, and PTGS2 for Tan I, while STAT3, AKT1, CCND1, MAPK14, VEGFA, ESR1, MAPK8 and AR for CST. Pathway enrichment analysis by DAVID database indicated that Tan I and CST principally regulated the inflammation-associated pathway, such as TLR, JAK-STAT signaling pathway, focal adhesion, apoptosis, mTOR signaling pathway. In vitro, we found that both Tan I and CST exerts significantly effect on LPS stimulated NO secretion and iNOS expression in macrophages. Taken together, our data elucidate that anti-inflammatory pharmacological activities of Tan I and CST may be predominantly related to inhibition of TLR signaling pathway and regulating iNOS synthesis. These findings highlight the predicted therapeutic targets may be potential targets of Tan I and CST for anti-inflammation treatment.

引用

页数：9

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