Berberine promotes M2 macrophage polarisation through the IL-4-STAT6 signalling pathway in ulcerative colitis treatment
Aim: This study focusses on the anti-inflammatory and immune-modulatory roles of berberine (BBR) in ulcerative colitis (UC) treatment. Additionally, the underlying mechanisms of BBR were systematically explored. Methods: A 3% (w/v) dextran sodium sulphate (DSS) solution was used for establishing the...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402301383X |
| _version_ | 1797851836336570368 |
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| author | Kai Xiong Jia Deng Tinghui Yue Wenting Hu Xinglin Zeng Tao Yang Tianbao Xiao |
| author_facet | Kai Xiong Jia Deng Tinghui Yue Wenting Hu Xinglin Zeng Tao Yang Tianbao Xiao |
| author_sort | Kai Xiong |
| collection | DOAJ |
| description | Aim: This study focusses on the anti-inflammatory and immune-modulatory roles of berberine (BBR) in ulcerative colitis (UC) treatment. Additionally, the underlying mechanisms of BBR were systematically explored. Methods: A 3% (w/v) dextran sodium sulphate (DSS) solution was used for establishing the mice UC model. M2 macrophage polarisation was induced in RAW 264.7 cells using interleukin 4 (IL-4), whereas M1 macrophage polarisation was induced using lipopolysaccharide. Colon length, colon mucosa damage index (CMDI), and haematoxylin–eosin (HE) staining were used to evaluate colon damage induced by DSS. M1/M2 macrophages in the colon tissue were identified using immunofluorescence (IF) staining with CD86+ or CD163+. M1/M2 macrophages in the abdomen were examined using flow cytometry. An enzyme-linked immunosorbent assay was conducted to identify M1/M2 macrophage supernatant biomarkers in RAW 264.7 cells. Western blotting, immunohistochemical staining, and real-time PCR were performed to investigate the potential mechanisms of BBR for treating UC in vivo and in vitro. Results: BBR was found to prolong colon length, ameliorate CMDI and alleviate the colon's pathological changes in UC mice. In DSS-induced UC mice, M1 macrophages predominated. BBR promoted M2 macrophages and suppressed M1 macrophages in the colon and abdomen of DSS-induced UC mice. Additionally, BBR significantly decreased M1-specific markers (IFN-γ and IL-1β) while increasing M2-specific markers (IL-10 and TGF-β) in the supernatants of RAW 264.7 cells. BBR upregulated the mRNA expression of IL-4, STAT6, and Chil3 while downregulating TNF-α, IFN-γ, and NOS2 expression in vivo. Moreover, BBR activated the downstream targets of the IL-4-STAT6 signalling pathway and enhanced the phosphorylation of STAT6 in vivo and in vitro to polarise M2 macrophage. Conclusion: In UC mice, BBR suppressed M1 macrophages while promoting M2 macrophages. M1 macrophage suppression and M2 macrophage activation were strongly correlated with the anti-inflammatory and immune-modulating activities of BBR. BBR induced the polarisation of M2 macrophages by activating the IL-4-STAT6 signalling pathway, which contributed to its therapeutic efficacy against UC. |
| first_indexed | 2024-04-09T19:23:10Z |
| format | Article |
| id | doaj.art-346cfb29a30548b7963253f7a78b304e |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-09T19:23:10Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-346cfb29a30548b7963253f7a78b304e2023-04-05T08:21:08ZengElsevierHeliyon2405-84402023-03-0193e14176Berberine promotes M2 macrophage polarisation through the IL-4-STAT6 signalling pathway in ulcerative colitis treatmentKai Xiong0Jia Deng1Tinghui Yue2Wenting Hu3Xinglin Zeng4Tao Yang5Tianbao Xiao6Colorectal and Anal Surgery, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No 71 Baoshan North Road, Guiyang, 550001, ChinaColorectal and Anal Surgery, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No 71 Baoshan North Road, Guiyang, 550001, ChinaColorectal and Anal Surgery, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No 71 Baoshan North Road, Guiyang, 550001, ChinaColorectal and Anal Surgery, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No 71 Baoshan North Road, Guiyang, 550001, ChinaColorectal and Anal Surgery, Chengdu Anorectal Hospital, Chengdu, 610075, ChinaColorectal and Anal Surgery, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No 71 Baoshan North Road, Guiyang, 550001, China; Corresponding author.Colorectal and Anal Surgery, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No 71 Baoshan North Road, Guiyang, 550001, China; Corresponding author.Aim: This study focusses on the anti-inflammatory and immune-modulatory roles of berberine (BBR) in ulcerative colitis (UC) treatment. Additionally, the underlying mechanisms of BBR were systematically explored. Methods: A 3% (w/v) dextran sodium sulphate (DSS) solution was used for establishing the mice UC model. M2 macrophage polarisation was induced in RAW 264.7 cells using interleukin 4 (IL-4), whereas M1 macrophage polarisation was induced using lipopolysaccharide. Colon length, colon mucosa damage index (CMDI), and haematoxylin–eosin (HE) staining were used to evaluate colon damage induced by DSS. M1/M2 macrophages in the colon tissue were identified using immunofluorescence (IF) staining with CD86+ or CD163+. M1/M2 macrophages in the abdomen were examined using flow cytometry. An enzyme-linked immunosorbent assay was conducted to identify M1/M2 macrophage supernatant biomarkers in RAW 264.7 cells. Western blotting, immunohistochemical staining, and real-time PCR were performed to investigate the potential mechanisms of BBR for treating UC in vivo and in vitro. Results: BBR was found to prolong colon length, ameliorate CMDI and alleviate the colon's pathological changes in UC mice. In DSS-induced UC mice, M1 macrophages predominated. BBR promoted M2 macrophages and suppressed M1 macrophages in the colon and abdomen of DSS-induced UC mice. Additionally, BBR significantly decreased M1-specific markers (IFN-γ and IL-1β) while increasing M2-specific markers (IL-10 and TGF-β) in the supernatants of RAW 264.7 cells. BBR upregulated the mRNA expression of IL-4, STAT6, and Chil3 while downregulating TNF-α, IFN-γ, and NOS2 expression in vivo. Moreover, BBR activated the downstream targets of the IL-4-STAT6 signalling pathway and enhanced the phosphorylation of STAT6 in vivo and in vitro to polarise M2 macrophage. Conclusion: In UC mice, BBR suppressed M1 macrophages while promoting M2 macrophages. M1 macrophage suppression and M2 macrophage activation were strongly correlated with the anti-inflammatory and immune-modulating activities of BBR. BBR induced the polarisation of M2 macrophages by activating the IL-4-STAT6 signalling pathway, which contributed to its therapeutic efficacy against UC.http://www.sciencedirect.com/science/article/pii/S240584402301383XUlcerative colitisBerberineInflammationMacrophages |
| spellingShingle | Kai Xiong Jia Deng Tinghui Yue Wenting Hu Xinglin Zeng Tao Yang Tianbao Xiao Berberine promotes M2 macrophage polarisation through the IL-4-STAT6 signalling pathway in ulcerative colitis treatment Heliyon Ulcerative colitis Berberine Inflammation Macrophages |
| title | Berberine promotes M2 macrophage polarisation through the IL-4-STAT6 signalling pathway in ulcerative colitis treatment |
| title_full | Berberine promotes M2 macrophage polarisation through the IL-4-STAT6 signalling pathway in ulcerative colitis treatment |
| title_fullStr | Berberine promotes M2 macrophage polarisation through the IL-4-STAT6 signalling pathway in ulcerative colitis treatment |
| title_full_unstemmed | Berberine promotes M2 macrophage polarisation through the IL-4-STAT6 signalling pathway in ulcerative colitis treatment |
| title_short | Berberine promotes M2 macrophage polarisation through the IL-4-STAT6 signalling pathway in ulcerative colitis treatment |
| title_sort | berberine promotes m2 macrophage polarisation through the il 4 stat6 signalling pathway in ulcerative colitis treatment |
| topic | Ulcerative colitis Berberine Inflammation Macrophages |
| url | http://www.sciencedirect.com/science/article/pii/S240584402301383X |
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