Wu-Tou Decoction in Rheumatoid Arthritis: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation

Frontiers in Pharmacology
Qingqing GuoAiping Lu

Abstract

Purpose: This study aimed to explore underlying action mechanism of Wu-Tou decoction (WTD) in rheumatoid arthritis (RA) through network pharmacology prediction and experimental verification. Methods: Chemical compounds and human target proteins of WTD as well as RA-related human genes were obtained from TCM Database @ Taiwan, PubChem and GenBank, respectively. Subsequently, molecular networks and canonical pathways presumably involved in the treatment of WTD on RA were generated by ingenuity pathway analysis (IPA) software. Furthermore, experimental validation was carried out with MIP-1β-induced U937 cell model and collagen induced arthritis (CIA) rat model. Results: CCR5 signaling pathway in macrophages was shown to be the top one shared signaling pathway associated with both cell immune response and cytokine signaling. In addition, protein kinase C (PKC) δ and p38 in this pathway were treated as target proteins of WTD in RA. In vitro experiments indicated that WTD inhibited MIP-1β-induced production of TNF-α, MIP-1α, and RANTES as well as phosphorylation of CCR5, PKC δ, and p38 in U937 cells. WTD treatment maintained the inhibitory effects on production of TNF-α and RANTES in MIP-1β-induced U937 cells after CCR5 knockdown. In...Continue Reading

References

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Citations

May 12, 2020·Journal of Leukocyte Biology·Qingqing GuoXiaojuan He
Dec 13, 2018·Evidence-based Complementary and Alternative Medicine : ECAM·Bin LiuCheng Lu
Apr 4, 2019·Chinese Journal of Integrative Medicine·Ting-Ting LuoJiao Guo
Apr 25, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Rong WuShi-Bing Su
Nov 22, 2019·Laboratory Investigation; a Journal of Technical Methods and Pathology·Xiang ZhangXiu-Wu Bian
Jan 24, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rong WuShi-Bing Su
Dec 24, 2017·International Immunopharmacology·Jing WangWeiguang Sun
Aug 17, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Mingrui HuJiekun Luo

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
PMA
ELISA
electrophoresis
PCR

Software Mentioned

UN
IPA
SCAN
IT
Leica QWin
Leica

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