Berberine inhibits IFN-γ signaling pathway in DSS-induced ulcerative colitis
Aims: The potential signaling pathways and core genes in ulcerative colitis (UC) were investigated in this study. Furthermore, potential mechanisms of BBR in treating UC were also explored. Methods: Expression profiling by array of UC patients were obtained from Gene Expression Omnibus (GEO) databas...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | Saudi Pharmaceutical Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319016422000950 |
| _version_ | 1818242429971595264 |
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| author | Tao Yang Xiao Ma Ruilin Wang Honghong Liu Shizhang Wei Manyi Jing Haotian Li Yanling Zhao |
| author_facet | Tao Yang Xiao Ma Ruilin Wang Honghong Liu Shizhang Wei Manyi Jing Haotian Li Yanling Zhao |
| author_sort | Tao Yang |
| collection | DOAJ |
| description | Aims: The potential signaling pathways and core genes in ulcerative colitis (UC) were investigated in this study. Furthermore, potential mechanisms of BBR in treating UC were also explored. Methods: Expression profiling by array of UC patients were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were determined with the differential analysis. The biological functions of DEGs were analyzed through the Database for Annotation, Visualization and Integrated Discovery (DAVID). The Gene Set Enrichment Analysis (GSEA) was applied to analyze the expression differences between two different phenotype sample sets. Dextran sulfate sodium (DSS) was applied to establish UC model of mice and lipopolysaccharide (LPS) was utilized to induce inflammatory damage of NCM460 cells. Therapeutic effects of berberine (BBR) on disease performance, pathologic changes and serum supernatant indices were analyzed in vivo. To further investigate the potential mechanisms of BBR in treating UC, the expression of genes and proteins in vivo and in vitro were examined by RT-qPCR, immunohistochemical staining and western blotting. Results: Immune-inflammatory genes were identified and up-regulated significantly in UC patients. In addition, IFN-γ signaling pathway and its core genes were significantly up-regulated in the phenotype of UC. All disease performance and the pathologic changes of UC in mice were evidently ameliorated by BBR treatment. The pro-inflammatory cytokines of serum, including CXCL9, CXCL1, IL-17 and TNF-α, in UC mice were significantly reduced by treatment of BBR. In terms of mechanisms of BBR in treating UC, the pro-inflammatory and immune-related genes, encoding IFN-γ, IRF8, NF-κB and TNF-α decreased significantly in UC mice followed by BBR treatment. Meanwhile, the expression of IFN-γ and its initiated targets, including IRF8, Ifit1, Ifit3, IRF1, were suppressed significantly by BBR treatment in vivo. The blocking of IFN-γ in vitro led to the silence of IFN-γ signaling pathway after exposure to BBR. Furthermore, the blocking of IFN-γ in vitro led to the silence of IFN-γ signaling pathway after exposure to BBR. Conclusion: BBR holds anti-inflammatory activity and can treat UC effectively. The anti-inflammatory property of BBR is tightly related to the suppression of IFN-γ signaling pathway, which is crucial in immune-inflammatory responses of the colon mucosa. |
| first_indexed | 2024-12-12T13:45:06Z |
| format | Article |
| id | doaj.art-d9592d76c8954f71ba786b837c1dfcce |
| institution | Directory Open Access Journal |
| issn | 1319-0164 |
| language | English |
| last_indexed | 2024-12-12T13:45:06Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Saudi Pharmaceutical Journal |
| spelling | doaj.art-d9592d76c8954f71ba786b837c1dfcce2022-12-22T00:22:43ZengElsevierSaudi Pharmaceutical Journal1319-01642022-06-01306764778Berberine inhibits IFN-γ signaling pathway in DSS-induced ulcerative colitisTao Yang0Xiao Ma1Ruilin Wang2Honghong Liu3Shizhang Wei4Manyi Jing5Haotian Li6Yanling Zhao7Colorectal and Anal Surgery, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No 71 Baoshan North Road, Guiyang 550001, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611100, ChinaIntegrative Medical Center, Chinese PLA General Hospital, Beijing 100039, ChinaDepartment of Policlinic, Chinese PLA General Hospital, Beijing 100039, ChinaDepartment of Pharmacy, Chinese PLA General Hospital, Beijing 100039, ChinaDepartment of Pharmacy, Chinese PLA General Hospital, Beijing 100039, ChinaDepartment of Pharmacy, Chinese PLA General Hospital, Beijing 100039, ChinaDepartment of Pharmacy, Chinese PLA General Hospital, Beijing 100039, China; Corresponding author at: Department of Pharmacy, Chinese PLA General Hospital, No 100 West Fourth Ring Middle Road Beijing, 100039, China.Aims: The potential signaling pathways and core genes in ulcerative colitis (UC) were investigated in this study. Furthermore, potential mechanisms of BBR in treating UC were also explored. Methods: Expression profiling by array of UC patients were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were determined with the differential analysis. The biological functions of DEGs were analyzed through the Database for Annotation, Visualization and Integrated Discovery (DAVID). The Gene Set Enrichment Analysis (GSEA) was applied to analyze the expression differences between two different phenotype sample sets. Dextran sulfate sodium (DSS) was applied to establish UC model of mice and lipopolysaccharide (LPS) was utilized to induce inflammatory damage of NCM460 cells. Therapeutic effects of berberine (BBR) on disease performance, pathologic changes and serum supernatant indices were analyzed in vivo. To further investigate the potential mechanisms of BBR in treating UC, the expression of genes and proteins in vivo and in vitro were examined by RT-qPCR, immunohistochemical staining and western blotting. Results: Immune-inflammatory genes were identified and up-regulated significantly in UC patients. In addition, IFN-γ signaling pathway and its core genes were significantly up-regulated in the phenotype of UC. All disease performance and the pathologic changes of UC in mice were evidently ameliorated by BBR treatment. The pro-inflammatory cytokines of serum, including CXCL9, CXCL1, IL-17 and TNF-α, in UC mice were significantly reduced by treatment of BBR. In terms of mechanisms of BBR in treating UC, the pro-inflammatory and immune-related genes, encoding IFN-γ, IRF8, NF-κB and TNF-α decreased significantly in UC mice followed by BBR treatment. Meanwhile, the expression of IFN-γ and its initiated targets, including IRF8, Ifit1, Ifit3, IRF1, were suppressed significantly by BBR treatment in vivo. The blocking of IFN-γ in vitro led to the silence of IFN-γ signaling pathway after exposure to BBR. Furthermore, the blocking of IFN-γ in vitro led to the silence of IFN-γ signaling pathway after exposure to BBR. Conclusion: BBR holds anti-inflammatory activity and can treat UC effectively. The anti-inflammatory property of BBR is tightly related to the suppression of IFN-γ signaling pathway, which is crucial in immune-inflammatory responses of the colon mucosa.http://www.sciencedirect.com/science/article/pii/S1319016422000950Ulcerative colitisBerberineIFN-γInflammation |
| spellingShingle | Tao Yang Xiao Ma Ruilin Wang Honghong Liu Shizhang Wei Manyi Jing Haotian Li Yanling Zhao Berberine inhibits IFN-γ signaling pathway in DSS-induced ulcerative colitis Saudi Pharmaceutical Journal Ulcerative colitis Berberine IFN-γ Inflammation |
| title | Berberine inhibits IFN-γ signaling pathway in DSS-induced ulcerative colitis |
| title_full | Berberine inhibits IFN-γ signaling pathway in DSS-induced ulcerative colitis |
| title_fullStr | Berberine inhibits IFN-γ signaling pathway in DSS-induced ulcerative colitis |
| title_full_unstemmed | Berberine inhibits IFN-γ signaling pathway in DSS-induced ulcerative colitis |
| title_short | Berberine inhibits IFN-γ signaling pathway in DSS-induced ulcerative colitis |
| title_sort | berberine inhibits ifn γ signaling pathway in dss induced ulcerative colitis |
| topic | Ulcerative colitis Berberine IFN-γ Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S1319016422000950 |
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