Qu-zhuo-tong-bi decoction exerts gouty arthritis therapy by skewing macrophage polarization through butanoate metabolism
Abstract Background Qu-zhuo-tong-bi decoction (QZTBD), a traditional Chinese medicine (TCM), has demonstrated efficacy in the treatment of gouty arthritis. However, to date, the precise pharmacological mechanisms remain unclear. Purpose The study aims to ascertain the therapeutic effects and the und...
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BMC
2025-07-01
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| Series: | Chinese Medicine |
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| Online Access: | https://doi.org/10.1186/s13020-025-01162-6 |
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| author | Siyue Song Xianghui Wen Fusen Chen Jiatao Li Kaiyue Shi Yu Lou Anyi Xu Chengping Wen Tiejuan Shao |
| author_facet | Siyue Song Xianghui Wen Fusen Chen Jiatao Li Kaiyue Shi Yu Lou Anyi Xu Chengping Wen Tiejuan Shao |
| author_sort | Siyue Song |
| collection | DOAJ |
| description | Abstract Background Qu-zhuo-tong-bi decoction (QZTBD), a traditional Chinese medicine (TCM), has demonstrated efficacy in the treatment of gouty arthritis. However, to date, the precise pharmacological mechanisms remain unclear. Purpose The study aims to ascertain the therapeutic effects and the underlying mechanisms of QZTBD in the treatment of gouty arthritis. Methods The efficacy and safety of different doses of QZTBD were investigated in Uox-KO mice. Candidate active ingredients were identified using UHPLC-MS/MS. The potential therapeutic pathways of the active ingredients were predicted through network pharmacology. The mechanisms of QZTBD in alleviating gouty arthritis were explored via comprehensive analyses of gut microbiota, combined with RT-qPCR, western blot, immunofluorescence, ELISA, flow cytometry, and Seahorse assay. Fecal microbiota transplantation (FMT), bacterial culture experiment, butyrate-producing bacteria (BPB) and butyrate administration, and 2-DG intervention were conducted to explore the roles of BPB and butanoate metabolism in gout progression and therapeutic mechanisms of QZTBD. In vitro studies further validated the regulatory effects of butyrate and QZTBD on macrophage polarization through glycolysis modulation. Results 18.0 g/kg/d of QZTBD effectively alleviated the symptoms of gouty arthritis with excellent hepatic and renal safety. UHPLC-MS/MS analysis and network pharmacology revealed that QZTBD exerts its effects on butanoate metabolism during gouty arthritis inflammation. QZTBD treatment increased the abundance of BPB, the levels of serum and colon butyrate, and the expression levels of Buk and But. The transplantation of QZTBD-treated microbiota reproduced the therapeutic effects of QZTBD. M1 macrophage polarization was suppressed after QZTBD intervention. The administration of BPB and butyrate attenuated gouty arthritis and orchestrated macrophage polarization. Inhibition of glycolysis regulated the phenotype of macrophage and attenuated inflammatory processes. In vitro analysis unveiled that QZTBD and butyrate modulated glycolysis to regulate macrophage polarization, thereby alleviating gouty arthritis. Conclusion QZTBD targeted butanoate metabolism to regulate macrophage polarization, thereby effectively alleviating intestinal inflammation and restoring immune homeostasis in gouty arthritis. These findings establish a mechanistic foundation for developing precision therapeutic strategies leveraging QZTBD to combat gouty arthritis. |
| format | Article |
| id | doaj-art-91297434e56b44e6a2a69e29be97056e |
| institution | DOAJ |
| issn | 1749-8546 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Chinese Medicine |
| spelling | doaj-art-91297434e56b44e6a2a69e29be97056e2025-08-20T03:06:05ZengBMCChinese Medicine1749-85462025-07-0120112010.1186/s13020-025-01162-6Qu-zhuo-tong-bi decoction exerts gouty arthritis therapy by skewing macrophage polarization through butanoate metabolismSiyue Song0Xianghui Wen1Fusen Chen2Jiatao Li3Kaiyue Shi4Yu Lou5Anyi Xu6Chengping Wen7Tiejuan Shao8College of Basic Medical Sciences, Zhejiang Chinese Medical UniversityCollege of Basic Medical Sciences, Zhejiang Chinese Medical UniversityCollege of Basic Medical Sciences, Zhejiang Chinese Medical UniversityCollege of Basic Medical Sciences, Zhejiang Chinese Medical UniversityCollege of Basic Medical Sciences, Zhejiang Chinese Medical UniversityCollege of Basic Medical Sciences, Zhejiang Chinese Medical UniversityFirst Clinical Medical College, Zhejiang Chinese Medical UniversityCollege of Basic Medical Sciences, Zhejiang Chinese Medical UniversityCollege of Basic Medical Sciences, Zhejiang Chinese Medical UniversityAbstract Background Qu-zhuo-tong-bi decoction (QZTBD), a traditional Chinese medicine (TCM), has demonstrated efficacy in the treatment of gouty arthritis. However, to date, the precise pharmacological mechanisms remain unclear. Purpose The study aims to ascertain the therapeutic effects and the underlying mechanisms of QZTBD in the treatment of gouty arthritis. Methods The efficacy and safety of different doses of QZTBD were investigated in Uox-KO mice. Candidate active ingredients were identified using UHPLC-MS/MS. The potential therapeutic pathways of the active ingredients were predicted through network pharmacology. The mechanisms of QZTBD in alleviating gouty arthritis were explored via comprehensive analyses of gut microbiota, combined with RT-qPCR, western blot, immunofluorescence, ELISA, flow cytometry, and Seahorse assay. Fecal microbiota transplantation (FMT), bacterial culture experiment, butyrate-producing bacteria (BPB) and butyrate administration, and 2-DG intervention were conducted to explore the roles of BPB and butanoate metabolism in gout progression and therapeutic mechanisms of QZTBD. In vitro studies further validated the regulatory effects of butyrate and QZTBD on macrophage polarization through glycolysis modulation. Results 18.0 g/kg/d of QZTBD effectively alleviated the symptoms of gouty arthritis with excellent hepatic and renal safety. UHPLC-MS/MS analysis and network pharmacology revealed that QZTBD exerts its effects on butanoate metabolism during gouty arthritis inflammation. QZTBD treatment increased the abundance of BPB, the levels of serum and colon butyrate, and the expression levels of Buk and But. The transplantation of QZTBD-treated microbiota reproduced the therapeutic effects of QZTBD. M1 macrophage polarization was suppressed after QZTBD intervention. The administration of BPB and butyrate attenuated gouty arthritis and orchestrated macrophage polarization. Inhibition of glycolysis regulated the phenotype of macrophage and attenuated inflammatory processes. In vitro analysis unveiled that QZTBD and butyrate modulated glycolysis to regulate macrophage polarization, thereby alleviating gouty arthritis. Conclusion QZTBD targeted butanoate metabolism to regulate macrophage polarization, thereby effectively alleviating intestinal inflammation and restoring immune homeostasis in gouty arthritis. These findings establish a mechanistic foundation for developing precision therapeutic strategies leveraging QZTBD to combat gouty arthritis.https://doi.org/10.1186/s13020-025-01162-6Qu-zhuo-tong-bi decoctionGouty arthritisGut microbiomeButanoate metabolismMacrophage polarizationGlycolysis |
| spellingShingle | Siyue Song Xianghui Wen Fusen Chen Jiatao Li Kaiyue Shi Yu Lou Anyi Xu Chengping Wen Tiejuan Shao Qu-zhuo-tong-bi decoction exerts gouty arthritis therapy by skewing macrophage polarization through butanoate metabolism Chinese Medicine Qu-zhuo-tong-bi decoction Gouty arthritis Gut microbiome Butanoate metabolism Macrophage polarization Glycolysis |
| title | Qu-zhuo-tong-bi decoction exerts gouty arthritis therapy by skewing macrophage polarization through butanoate metabolism |
| title_full | Qu-zhuo-tong-bi decoction exerts gouty arthritis therapy by skewing macrophage polarization through butanoate metabolism |
| title_fullStr | Qu-zhuo-tong-bi decoction exerts gouty arthritis therapy by skewing macrophage polarization through butanoate metabolism |
| title_full_unstemmed | Qu-zhuo-tong-bi decoction exerts gouty arthritis therapy by skewing macrophage polarization through butanoate metabolism |
| title_short | Qu-zhuo-tong-bi decoction exerts gouty arthritis therapy by skewing macrophage polarization through butanoate metabolism |
| title_sort | qu zhuo tong bi decoction exerts gouty arthritis therapy by skewing macrophage polarization through butanoate metabolism |
| topic | Qu-zhuo-tong-bi decoction Gouty arthritis Gut microbiome Butanoate metabolism Macrophage polarization Glycolysis |
| url | https://doi.org/10.1186/s13020-025-01162-6 |
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