Chinese medicine Huzhen tongfeng formula effectively attenuates gouty arthritis by inhibiting arachidonic acid metabolism and inflammatory mediators

Deng, J; Wu, Z; Chen, C; Zhao, Z; Wang, Y; Lin, Y; Wang, Z

Chinese medicine Huzhen tongfeng formula effectively attenuates gouty arthritis by inhibiting arachidonic acid metabolism and inflammatory mediators

Deng, J Wu, Z Chen, C Zhao, Z Wang, Y Lin, Y

Wang, Z

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Publisher:: Hindawi Publishing Corporation
Publication Type:: Journal Article
Citation:: Mediators of Inflammation, 2020
Issue Date:: 2020-07-30

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Field	Value	Language
dc.contributor.author	Deng, J
dc.contributor.author	Wu, Z
dc.contributor.author	Chen, C
dc.contributor.author	Zhao, Z
dc.contributor.author	Wang, Y
dc.contributor.author	Lin, Y https://orcid.org/0000-0002-4637-9701
dc.contributor.author	Wang, Z
dc.date.accessioned	2020-10-10T15:46:31Z
dc.date.available	2020-10-10T15:46:31Z
dc.date.issued	2020-07-30
dc.identifier.citation	Mediators of Inflammation, 2020
dc.identifier.issn	0962-9351
dc.identifier.uri	http://hdl.handle.net/10453/143211
dc.description.abstract	The Chinese herbal medicine, Huzhen Tongfeng Formula (HZTF), derived from traditional Chinese medicine (TCM) practice, has recognized therapeutic benefits for gouty arthritis (GA). HZTF is currently in the late stage of approval process as a new anti-GA drug application. However, the underlying mechanism of HZTF as an anti-gout medication is unclear. In this study, we combined network pharmacology and experimental validation approaches to elucidate the mechanism of action of HZTF. First, the relative drug-disease target networks were constructed and analyzed for pathway enrichment. Potential pathways were then validated by in vitro and in vivo experiments. We found that 34 compounds from HZTF matched 181 potential drug targets. Topology analysis revealed 77 core targets of HZTF, which were highly related to gout, following screening of KEGG pathway enrichment. Further analysis demonstrated that the arachidonic acid metabolic pathway was the most relevant pathway involved in the mechanism of HZTF. Validation experiments showed that HZTF significantly inhibited the inflammatory cell infiltration into gouty joints, improved the swelling of affected joints, and increased the pain threshold. HZTF significantly reduced the transcription and production of various cytokines and inflammatory mediators in vitro. In particular, cyclooxygenase (COX)-1, COX-2, and 5-lipoxygenase were simultaneously down-regulated. In conclusion, our study suggests that the anti-gout mechanism of HZTF is associated with the inhibition of the arachidonic acid pathway, resulting in the suppression of inflammatory cytokines and mediators. These findings extend our understanding of the pharmacological action of HZTF, rationalizing the application HZTF as an effective herbal therapy for GA.
dc.language	en
dc.publisher	Hindawi Publishing Corporation
dc.relation	Precision Medicine and Healthcare (Beijing) Science and Technology Co. Ltd
dc.relation.ispartof	Mediators of Inflammation
dc.rights	info:eu-repo/semantics/openAccess
dc.rights	Copyright © 2020 Jianping Deng et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.subject	1107 Immunology
dc.subject.classification	Immunology
dc.title	Chinese medicine Huzhen tongfeng formula effectively attenuates gouty arthritis by inhibiting arachidonic acid metabolism and inflammatory mediators
dc.type	Journal Article
utslib.for	1107 Immunology
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2020-10-10T15:45:28Z
pubs.publication-status	Accepted

Abstract:

The Chinese herbal medicine, Huzhen Tongfeng Formula (HZTF), derived from traditional Chinese medicine (TCM) practice, has recognized therapeutic benefits for gouty arthritis (GA). HZTF is currently in the late stage of approval process as a new anti-GA drug application. However, the underlying mechanism of HZTF as an anti-gout medication is unclear. In this study, we combined network pharmacology and experimental validation approaches to elucidate the mechanism of action of HZTF. First, the relative drug-disease target networks were constructed and analyzed for pathway enrichment. Potential pathways were then validated by in vitro and in vivo experiments. We found that 34 compounds from HZTF matched 181 potential drug targets. Topology analysis revealed 77 core targets of HZTF, which were highly related to gout, following screening of KEGG pathway enrichment. Further analysis demonstrated that the arachidonic acid metabolic pathway was the most relevant pathway involved in the mechanism of HZTF. Validation experiments showed that HZTF significantly inhibited the inflammatory cell infiltration into gouty joints, improved the swelling of affected joints, and increased the pain threshold. HZTF significantly reduced the transcription and production of various cytokines and inflammatory mediators in vitro. In particular, cyclooxygenase (COX)-1, COX-2, and 5-lipoxygenase were simultaneously down-regulated. In conclusion, our study suggests that the anti-gout mechanism of HZTF is associated with the inhibition of the arachidonic acid pathway, resulting in the suppression of inflammatory cytokines and mediators. These findings extend our understanding of the pharmacological action of HZTF, rationalizing the application HZTF as an effective herbal therapy for GA.

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http://hdl.handle.net/10453/143211