Chinese Medicine Huzhen Tongfeng Formula Effectively Attenuates Gouty Arthritis by Inhibiting Arachidonic Acid Metabolism and Inflammatory Mediators

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 mech...

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Main Authors: Jianping Deng, Zicong Wu, Chen Chen, Zhenling Zhao, Yifei Li, Zhengquan Su, Yiguang Lin, Yifei Wang, Zhiping Wang
Format: Article
Language:English
Published: Hindawi Limited 2020-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2020/6950206
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record_format Article
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language English
format Article
sources DOAJ
author Jianping Deng
Zicong Wu
Chen Chen
Zhenling Zhao
Yifei Li
Zhengquan Su
Yiguang Lin
Yifei Wang
Zhiping Wang
spellingShingle Jianping Deng
Zicong Wu
Chen Chen
Zhenling Zhao
Yifei Li
Zhengquan Su
Yiguang Lin
Yifei Wang
Zhiping Wang
Chinese Medicine Huzhen Tongfeng Formula Effectively Attenuates Gouty Arthritis by Inhibiting Arachidonic Acid Metabolism and Inflammatory Mediators
Mediators of Inflammation
author_facet Jianping Deng
Zicong Wu
Chen Chen
Zhenling Zhao
Yifei Li
Zhengquan Su
Yiguang Lin
Yifei Wang
Zhiping Wang
author_sort Jianping Deng
title Chinese Medicine Huzhen Tongfeng Formula Effectively Attenuates Gouty Arthritis by Inhibiting Arachidonic Acid Metabolism and Inflammatory Mediators
title_short Chinese Medicine Huzhen Tongfeng Formula Effectively Attenuates Gouty Arthritis by Inhibiting Arachidonic Acid Metabolism and Inflammatory Mediators
title_full Chinese Medicine Huzhen Tongfeng Formula Effectively Attenuates Gouty Arthritis by Inhibiting Arachidonic Acid Metabolism and Inflammatory Mediators
title_fullStr Chinese Medicine Huzhen Tongfeng Formula Effectively Attenuates Gouty Arthritis by Inhibiting Arachidonic Acid Metabolism and Inflammatory Mediators
title_full_unstemmed Chinese Medicine Huzhen Tongfeng Formula Effectively Attenuates Gouty Arthritis by Inhibiting Arachidonic Acid Metabolism and Inflammatory Mediators
title_sort chinese medicine huzhen tongfeng formula effectively attenuates gouty arthritis by inhibiting arachidonic acid metabolism and inflammatory mediators
publisher Hindawi Limited
series Mediators of Inflammation
issn 0962-9351
1466-1861
publishDate 2020-01-01
description 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 antigout 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 downregulated. In conclusion, our study suggests that the antigout 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.
url http://dx.doi.org/10.1155/2020/6950206
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spelling doaj-540ec260c8a54d0aa4523f44bb85828a2020-11-25T01:40:32ZengHindawi LimitedMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/69502066950206Chinese Medicine Huzhen Tongfeng Formula Effectively Attenuates Gouty Arthritis by Inhibiting Arachidonic Acid Metabolism and Inflammatory MediatorsJianping Deng0Zicong Wu1Chen Chen2Zhenling Zhao3Yifei Li4Zhengquan Su5Yiguang Lin6Yifei Wang7Zhiping Wang8Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Department of Pharmaceutics, Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Department of Pharmaceutics, Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Department of Pharmaceutics, Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou, ChinaGuangzhou Jinan Biomedical Research and Development Center, Guangzhou, ChinaGuangzhou Jinan Biomedical Research and Development Center, Guangzhou, ChinaGuangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Department of Pharmaceutics, Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Life Sciences, University of Technology Sydney, Broadway, NSW, AustraliaGuangzhou Jinan Biomedical Research and Development Center, Guangzhou, ChinaGuangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Department of Pharmaceutics, Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou, ChinaThe 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 antigout 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 downregulated. In conclusion, our study suggests that the antigout 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.http://dx.doi.org/10.1155/2020/6950206