Gandouling ameliorates Wilson’s disease-associated liver fibrosis in mice with associated faecal microbiome and metabolome remodeling
IntroductionIndividuals with Wilson's disease (WD) exhibit liver fibrosis, a basic pathological change that was recently demonstrated to be dynamic and reversible. The gut microbiota markedly influences the occurrence of WD. Gandouling (GDL), a standardized Chinese herbal formula, has demonstra...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Pharmacology |
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| author | Lulu Tang Wei Dong Danqing Liu Chenling Zhao Jie Chen Yuya Wen Jingyu Zeng Ting Dong Wenming Yang Wenming Yang |
| author_facet | Lulu Tang Wei Dong Danqing Liu Chenling Zhao Jie Chen Yuya Wen Jingyu Zeng Ting Dong Wenming Yang Wenming Yang |
| author_sort | Lulu Tang |
| collection | DOAJ |
| description | IntroductionIndividuals with Wilson's disease (WD) exhibit liver fibrosis, a basic pathological change that was recently demonstrated to be dynamic and reversible. The gut microbiota markedly influences the occurrence of WD. Gandouling (GDL), a standardized Chinese herbal formula, has demonstrated an anti-fibrotic effect against WD-associated liver fibrosis. We sought to determine whether GDL may prevent liver fibrosis in toxic milk (TX) mice by assessing its ability to regulate gut microbiota, metabolites, and barrier function.MethodsTX male mice aged 6 months were analysed. GDL was administered at varying doses over a 6-week period. The biochemical indexes related to liver function, fibrosis, and inflammation were determined using commercial assay kits. Histological analyses and immunohistochemistry staining, were performed to evaluate the histopathological changes and collagen deposition in mouse liver tissues. Additionally, to detect alterations in the intestinal bacterial composition and metabolites, faecal samples were examined using non-targeted metabolomics and 16S rRNA sequencing.ResultsThe administration of GDL demonstrated anti-fibrotic effects on the liver, decreased serum inflammatory markers, ameliorated liver histopathology, and restored ileal permeability in the model group, as compared to the control group. Furthermore, a medium dosage of GDL treatment significantly rebalance microbiota composition and function and modulated lipid and lipid-like molecule levels.DiscussionModulating intestinal homeostasis is a promising approach for treating liver fibrosis in patients with WD. Therefore, GDL may serve as a useful agent for treating WD-associated liver fibrosis. |
| format | Article |
| id | doaj-art-25ed429d5f2a410db9c624f30a5eb2ff |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj-art-25ed429d5f2a410db9c624f30a5eb2ff2025-08-20T02:05:17ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.15861711586171Gandouling ameliorates Wilson’s disease-associated liver fibrosis in mice with associated faecal microbiome and metabolome remodelingLulu Tang0Wei Dong1Danqing Liu2Chenling Zhao3Jie Chen4Yuya Wen5Jingyu Zeng6Ting Dong7Wenming Yang8Wenming Yang9Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, ChinaDepartment of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, ChinaDepartment of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, ChinaDepartment of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, ChinaDepartment of Neurology, Wuhan Hospital of Traditonal Chinese Medicine, Wuhan, Hubei, ChinaDepartment of Medical Technology, Clinical College of Anhui Medical University, Hefei, Anhui, ChinaDepartment of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, ChinaDepartment of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, ChinaDepartment of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, ChinaKey Laboratory of Xin'an Medicine Ministry of Education, Hefei, Anhui, ChinaIntroductionIndividuals with Wilson's disease (WD) exhibit liver fibrosis, a basic pathological change that was recently demonstrated to be dynamic and reversible. The gut microbiota markedly influences the occurrence of WD. Gandouling (GDL), a standardized Chinese herbal formula, has demonstrated an anti-fibrotic effect against WD-associated liver fibrosis. We sought to determine whether GDL may prevent liver fibrosis in toxic milk (TX) mice by assessing its ability to regulate gut microbiota, metabolites, and barrier function.MethodsTX male mice aged 6 months were analysed. GDL was administered at varying doses over a 6-week period. The biochemical indexes related to liver function, fibrosis, and inflammation were determined using commercial assay kits. Histological analyses and immunohistochemistry staining, were performed to evaluate the histopathological changes and collagen deposition in mouse liver tissues. Additionally, to detect alterations in the intestinal bacterial composition and metabolites, faecal samples were examined using non-targeted metabolomics and 16S rRNA sequencing.ResultsThe administration of GDL demonstrated anti-fibrotic effects on the liver, decreased serum inflammatory markers, ameliorated liver histopathology, and restored ileal permeability in the model group, as compared to the control group. Furthermore, a medium dosage of GDL treatment significantly rebalance microbiota composition and function and modulated lipid and lipid-like molecule levels.DiscussionModulating intestinal homeostasis is a promising approach for treating liver fibrosis in patients with WD. Therefore, GDL may serve as a useful agent for treating WD-associated liver fibrosis.https://www.frontiersin.org/articles/10.3389/fphar.2025.1586171/fullGandoulingWilson’s diseaseliver fibrosistoxic milk micegut microbiota |
| spellingShingle | Lulu Tang Wei Dong Danqing Liu Chenling Zhao Jie Chen Yuya Wen Jingyu Zeng Ting Dong Wenming Yang Wenming Yang Gandouling ameliorates Wilson’s disease-associated liver fibrosis in mice with associated faecal microbiome and metabolome remodeling Frontiers in Pharmacology Gandouling Wilson’s disease liver fibrosis toxic milk mice gut microbiota |
| title | Gandouling ameliorates Wilson’s disease-associated liver fibrosis in mice with associated faecal microbiome and metabolome remodeling |
| title_full | Gandouling ameliorates Wilson’s disease-associated liver fibrosis in mice with associated faecal microbiome and metabolome remodeling |
| title_fullStr | Gandouling ameliorates Wilson’s disease-associated liver fibrosis in mice with associated faecal microbiome and metabolome remodeling |
| title_full_unstemmed | Gandouling ameliorates Wilson’s disease-associated liver fibrosis in mice with associated faecal microbiome and metabolome remodeling |
| title_short | Gandouling ameliorates Wilson’s disease-associated liver fibrosis in mice with associated faecal microbiome and metabolome remodeling |
| title_sort | gandouling ameliorates wilson s disease associated liver fibrosis in mice with associated faecal microbiome and metabolome remodeling |
| topic | Gandouling Wilson’s disease liver fibrosis toxic milk mice gut microbiota |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1586171/full |
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