UPLC-Q-TOF-MS/MS combined with network pharmacology for exploring antiinflammatory mechanism of Eurycoma longifolia.
10.12122/j.issn.1673-4254.2023.06.02
- Author:
Fang LIU
1
;
Yuanfang ZHANG
1
;
Peng LIU
1
;
Jiamin LIU
1
;
Siyu LIU
1
;
Junjie WANG
1
Author Information
1. College of Pharmacy, Xiangnan University, Chenzhou 423000, China.
- Publication Type:Journal Article
- Keywords:
Eurycoma longifolia Jack;
anti-inflammation;
molecular docking;
network pharmacology;
pharmacological activity
- MeSH:
Animals;
Mice;
Network Pharmacology;
Eurycoma;
Lipopolysaccharides;
Molecular Docking Simulation;
Tandem Mass Spectrometry;
Anti-Inflammatory Agents/pharmacology*;
Ethanol;
Plant Extracts/pharmacology*
- From:
Journal of Southern Medical University
2023;43(6):879-888
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the mechanisms that mediate the anti-inflammatory activity of Eurycoma longifolia.
METHODS:Kunming mouse models of xylene-induced ear swelling and lipopolysaccharide (LPS)-induced acute pneumonia were used to compare the anti- inflammatory activities of aqueous and ethanol extracts of Eurycoma longifolia. UPLC-Q-TOF-MS/MS was used to identify the chemical composition in the ethanol extract of Eurycoma longifolia, based on which the potential antiinflammatory targets of Eurycoma longifolia were screened using the databases including SwissADME, SwissTargetPrediction, and Genecards. The String database was used to generate the protein-protein interaction (PPI) network, and Cytoscape was used for network topology analysis and screening the core targets. The enrichment of the core targets was analyzed using Metascape database, the core components and targets were docked with Autodock software, and the docking results were visualized using Pymol software. In a RAW264.7 cell model of LPS-induced inflammation, the Griess reagent was used to measure NO level, and Western blotting was performed to detect the expression levels of MAPK1, JAK2, and STAT3 proteins to verify the anti- inflammatory mechanism of Eurycoma longifolia.
RESULTS:The ethanol extract (75%) of Eurycoma longifolia (ELE) was the active site, which contained a total of 37 chemical components. These chemical compounds and diseases had 541 targets, involving the JAK/STAT3, cAMP and other signaling pathways. Twelve indicator components were identified, which all showed good results of molecular docking with two core targets involved in the signaling pathways. In the cell validation experiment, treatment of the cells with low-, medium-, and high-dose ELE significantly reduced NO release in the cells, and ELE at the medium dose significantly decreased the cellular expressions of JAK2 and STAT3.
CONCLUSION:The anti-inflammatory activity of Eurycoma longifolia is attributed primarily to its active ingredients bitter lignin and alkaloids, which may regulate the JAK/STAT3 signaling pathway by targeting JAK2 and STAT3.
