TY - JOUR
T1 - Anti-inflammatory effects of Zhishi and Zhiqiao revealed by network pharmacology integrated with molecular mechanism and metabolomics studies
AU - Zhao, Siyu
AU - Liu, Zhenli
AU - Wang, Menglei
AU - He, Dan
AU - Liu, Linlin
AU - Shu, Yisong
AU - Song, Zhiqian
AU - Li, Hui
AU - Liu, Yuanyan
AU - Lyu, Aiping
N1 - Funding Information:
This study was financially supported by the National Natural Science Foundation of China (Project No. 81573569, 81470177, 81001623 and 81373773) , fundamental research funds for the central public welfare research institutes (grant No. YZ-1811) and also supported by the long-term subsidy mechanism from the Ministry of Finance and the Ministry of Education of PRC for BUCT.
Publisher copyright:
© 2018 Elsevier GmbH. All rights reserved.
PY - 2018/11/15
Y1 - 2018/11/15
N2 - Background: The inflammatory response has a complex pathogenesis; thus, it is a critical contributor to the development and complication of many diseases. Zhishi and Zhiqiao are famous Citrus herbal medicines that are rich in bioactive phenolic constituents with multiple anti-inflammatory activities. Purpose: Establishment of a multi-component-target-pathway network strategy to investigate the usage of Zhishi and Zhiqiao on inflammatory diseases can provide a reference for mechanisms of traditional Chinese medicine (TCM). Study Design: A multi-component-target-pathway network strategy was constructed to elucidate the various antiinflammatory effects of Zhishi and Zhiqiao by integrating multi-constituent determination, network pharmacology, molecular mechanisms in cells and integrated metabolomics in animals. Methods: Based on the quantitatively determined global and characteristic chemical profiles of Zhishi and Zhiqiao, the component-target-pathway network was predicted by network pharmacology coupled with text mining and docking. The potential antiinflammatory mechanism of the various components in Zhishi and Zhiqiao were verified using LPS-induced inflammatory responses in RAW 264.7 cells. The different metabolic regulating effects of Zhishi and Zhiqiao against an LPS-induced inflammation model were investigated using a plasma metabolomics strategy. Results: The molecular mechanism of Zhishi mainly suppressed the MAPK signaling pathway, whereas Zhiqiao emphasized the PPAR-AKT signaling pathways simultaneously to block the inflammatory process. Meanwhile, Zhishi and Zhiqiao both exhibited an anti-inflammatory effect by inhibiting the NF-κB signaling pathway to reduce the production of inflammatory mediators. In the metabolomics study, Zhishi and Zhiqiao exhibited variant corrections of the disordered metabolic pathways through amino acid metabolism, glycometabolism and lipid metabolism. Conclusion: All of these results indicate that Zhishi and Zhiqiao, in a diversified mixture, exert their anti-inflammatory effect through variant pathways. These findings can assist in developing the use of Zhishi and Zhiqiao for inflammatory diseases.
AB - Background: The inflammatory response has a complex pathogenesis; thus, it is a critical contributor to the development and complication of many diseases. Zhishi and Zhiqiao are famous Citrus herbal medicines that are rich in bioactive phenolic constituents with multiple anti-inflammatory activities. Purpose: Establishment of a multi-component-target-pathway network strategy to investigate the usage of Zhishi and Zhiqiao on inflammatory diseases can provide a reference for mechanisms of traditional Chinese medicine (TCM). Study Design: A multi-component-target-pathway network strategy was constructed to elucidate the various antiinflammatory effects of Zhishi and Zhiqiao by integrating multi-constituent determination, network pharmacology, molecular mechanisms in cells and integrated metabolomics in animals. Methods: Based on the quantitatively determined global and characteristic chemical profiles of Zhishi and Zhiqiao, the component-target-pathway network was predicted by network pharmacology coupled with text mining and docking. The potential antiinflammatory mechanism of the various components in Zhishi and Zhiqiao were verified using LPS-induced inflammatory responses in RAW 264.7 cells. The different metabolic regulating effects of Zhishi and Zhiqiao against an LPS-induced inflammation model were investigated using a plasma metabolomics strategy. Results: The molecular mechanism of Zhishi mainly suppressed the MAPK signaling pathway, whereas Zhiqiao emphasized the PPAR-AKT signaling pathways simultaneously to block the inflammatory process. Meanwhile, Zhishi and Zhiqiao both exhibited an anti-inflammatory effect by inhibiting the NF-κB signaling pathway to reduce the production of inflammatory mediators. In the metabolomics study, Zhishi and Zhiqiao exhibited variant corrections of the disordered metabolic pathways through amino acid metabolism, glycometabolism and lipid metabolism. Conclusion: All of these results indicate that Zhishi and Zhiqiao, in a diversified mixture, exert their anti-inflammatory effect through variant pathways. These findings can assist in developing the use of Zhishi and Zhiqiao for inflammatory diseases.
KW - Anti-inflammatory mechanism
KW - Metabolomics
KW - Network pharmacology
KW - Zhiqiao
KW - Zhishi
UR - http://www.scopus.com/inward/record.url?scp=85054299888&partnerID=8YFLogxK
U2 - 10.1016/j.phymed.2018.09.184
DO - 10.1016/j.phymed.2018.09.184
M3 - Journal article
C2 - 30466993
AN - SCOPUS:85054299888
SN - 0944-7113
VL - 50
SP - 61
EP - 72
JO - Phytomedicine
JF - Phytomedicine
ER -