Affiliation:
1. Tianjin Medical University, General Hospital, Tianjin, 300052, China
2. Tianjin Key Laboratory of Blood Disease Cell
Therapy, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases,
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical
College, China
Abstract
Background:
HongTeng Decoction (HTD) is a traditional Chinese medicine that is
widely used to treat bacterial infections and chronic inflammation. However, its pharmacological
mechanism is not clear. Here, network pharmacology and experimental verification were applied
to investigate the drug targets and potential mechanisms of HTD in inflammation treatment.
Methods:
The active ingredients of HTD were collected from the multi-source databases and clarified
by Q Exactive Orbitrap analysis in the treatment of inflammation. Then, molecular docking
technology was used to explore the binding ability of key active ingredients and targets in HTD.
In vitro experiments, the inflammatory factors and MAPK signaling pathways are detected to verify
the anti-inflammatory effect of HTD on the RAW264.7 cells. Finally, the anti-inflammatory
effect of HTD was evaluated in LPS induced mice model.
Result:
A total of 236 active compounds and 492 targets of HTD were obtained through database
screening, and 954 potential targets of inflammation were identified. Finally, 164 possible targets
of HTD acting on inflammation were obtained. The PPI analysis and KEGG enrichment analyses
showed that the targets of HTD in inflammation were mostly related to the MAPK signaling
pathway, the IL-17 signaling pathway, and the TNF signaling pathway. By integrating the results
of the network analysis, the core targets of HTD in inflammation mainly include MAPK3, TNF,
MMP9, IL6, EGFR, and NFKBIA. The molecular docking results indicated solid binding activity
between MAPK3-naringenin and MAPK3-paeonol. It has been shown that HTD could inhibit the
levels of inflammatory factors, IL6 and TNF-α, as well as the splenic index in the LPS-stimulated
mice. Moreover, HTD could regulate protein expression levels of p-JNK1/2, and p-ERK1/2,
which reflects the inhibitory effect of HTD on the MAPKS signaling pathway.
Conclusion:
Our study is expected to provide the pharmacological mechanisms by which HTD
may be a promising anti-inflammatory drug for future clinical trials.
Funder
Scientific Foundation of Tianjin Municipal Education Commission
National Natural Science Foundation of China
Tianjin Health and Wellness Project
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Molecular Medicine,General Medicine