Salidroside alleviates ulcerative colitis via inhibiting macrophage pyroptosis and repairing the dysbacteriosis‐associated Th17/Treg imbalance
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by flora disequilibrium and mucosal immunity disorder. Here, we report that salidroside effectively restricts experimental colitis from two aspects of intestinal macrophage pyroptosis and dysbacteriosis‐derived colonic Th1...
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| Veröffentlicht in: | Phytotherapy research 2023-02, Vol.37 (2), p.367-382 |
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| creator | Liu, Xiaoman Zhou, Mingxia Dai, Zhenzhen Luo, Shangjian Shi, Yingying He, Zhenjuan Chen, Yingwei |
| description | Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by flora disequilibrium and mucosal immunity disorder. Here, we report that salidroside effectively restricts experimental colitis from two aspects of intestinal macrophage pyroptosis and dysbacteriosis‐derived colonic Th17/Treg imbalance. In innate immunity, the upregulated TREM1 and pyroptosis‐related proteins in inflamed colons were inhibited by salidroside administration and further experiments in vitro showed that salidroside suppressed LPS/ATP‐induced bone marrow‐derived macrophages (BMDMs) pyroptosis evident by the decline of LDH and IL‐1β release as well as the protein level of NLRP3, caspase‐1, and GSDMD p30. Moreover, the TREM1 inhibitor weakened the effect of salidroside on BMDMs pyroptosis, whereas salidroside still could downregulate TREM1 when NLRP3 was inhibited. In adaptive immunity, salidroside improved the gut microflora diversity and Th17/Treg ratio in DSS‐induced mice, especially promoting the abundance of Firmicutes. Clearance of the gut flora blocked the benefit of salidroside on colonic inflammation and Th17/Treg adaptive immunity, but transplanting salidroside‐treated foecal bacterium into flora‐depleted wild mice reproduced the resistance of salidroside to gut inflammation. Taken together, our data demonstrated that salidroside protected experimental colitis via skewing macrophage pyroptosis and Th17/Treg balance, indicating its potential effect on UC and other immune disorders. |
| doi_str_mv | 10.1002/ptr.7636 |
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Here, we report that salidroside effectively restricts experimental colitis from two aspects of intestinal macrophage pyroptosis and dysbacteriosis‐derived colonic Th17/Treg imbalance. In innate immunity, the upregulated TREM1 and pyroptosis‐related proteins in inflamed colons were inhibited by salidroside administration and further experiments in vitro showed that salidroside suppressed LPS/ATP‐induced bone marrow‐derived macrophages (BMDMs) pyroptosis evident by the decline of LDH and IL‐1β release as well as the protein level of NLRP3, caspase‐1, and GSDMD p30. Moreover, the TREM1 inhibitor weakened the effect of salidroside on BMDMs pyroptosis, whereas salidroside still could downregulate TREM1 when NLRP3 was inhibited. In adaptive immunity, salidroside improved the gut microflora diversity and Th17/Treg ratio in DSS‐induced mice, especially promoting the abundance of Firmicutes. Clearance of the gut flora blocked the benefit of salidroside on colonic inflammation and Th17/Treg adaptive immunity, but transplanting salidroside‐treated foecal bacterium into flora‐depleted wild mice reproduced the resistance of salidroside to gut inflammation. Taken together, our data demonstrated that salidroside protected experimental colitis via skewing macrophage pyroptosis and Th17/Treg balance, indicating its potential effect on UC and other immune disorders.</description><identifier>ISSN: 0951-418X</identifier><identifier>EISSN: 1099-1573</identifier><identifier>DOI: 10.1002/ptr.7636</identifier><identifier>PMID: 36331009</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Adaptive immunity ; Animals ; Bone marrow ; Caspase ; Colitis - chemically induced ; Colitis, Ulcerative - chemically induced ; Colitis, Ulcerative - drug therapy ; Dextran Sulfate - adverse effects ; Digestive system ; Dysbacteriosis ; Dysbiosis ; Flora ; Gastrointestinal tract ; gut microbiota ; Helper cells ; IBD ; Immune clearance ; Immunity ; Inflammation - metabolism ; Inflammatory bowel disease ; Inflammatory bowel diseases ; Innate immunity ; Intestinal microflora ; Lymphocytes T ; Macrophages ; Macrophages - metabolism ; Mice ; Mice, Inbred C57BL ; Mucosal immunity ; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism ; Proteins ; Pyroptosis ; Salidroside ; T-Lymphocytes, Regulatory - metabolism ; TREM1 signalling ; Triggering Receptor Expressed on Myeloid Cells-1 - metabolism ; Ulcerative colitis</subject><ispartof>Phytotherapy research, 2023-02, Vol.37 (2), p.367-382</ispartof><rights>2022 John Wiley & Sons Ltd.</rights><rights>2023 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4156-cb41843c2e2eafaa801d6fa470071ec5d15493f188502b0acd62b8be28cdcc883</citedby><cites>FETCH-LOGICAL-c4156-cb41843c2e2eafaa801d6fa470071ec5d15493f188502b0acd62b8be28cdcc883</cites><orcidid>0000-0002-2371-4570</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fptr.7636$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fptr.7636$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36331009$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Xiaoman</creatorcontrib><creatorcontrib>Zhou, Mingxia</creatorcontrib><creatorcontrib>Dai, Zhenzhen</creatorcontrib><creatorcontrib>Luo, Shangjian</creatorcontrib><creatorcontrib>Shi, Yingying</creatorcontrib><creatorcontrib>He, Zhenjuan</creatorcontrib><creatorcontrib>Chen, Yingwei</creatorcontrib><title>Salidroside alleviates ulcerative colitis via inhibiting macrophage pyroptosis and repairing the dysbacteriosis‐associated Th17/Treg imbalance</title><title>Phytotherapy research</title><addtitle>Phytother Res</addtitle><description>Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by flora disequilibrium and mucosal immunity disorder. Here, we report that salidroside effectively restricts experimental colitis from two aspects of intestinal macrophage pyroptosis and dysbacteriosis‐derived colonic Th17/Treg imbalance. In innate immunity, the upregulated TREM1 and pyroptosis‐related proteins in inflamed colons were inhibited by salidroside administration and further experiments in vitro showed that salidroside suppressed LPS/ATP‐induced bone marrow‐derived macrophages (BMDMs) pyroptosis evident by the decline of LDH and IL‐1β release as well as the protein level of NLRP3, caspase‐1, and GSDMD p30. Moreover, the TREM1 inhibitor weakened the effect of salidroside on BMDMs pyroptosis, whereas salidroside still could downregulate TREM1 when NLRP3 was inhibited. In adaptive immunity, salidroside improved the gut microflora diversity and Th17/Treg ratio in DSS‐induced mice, especially promoting the abundance of Firmicutes. Clearance of the gut flora blocked the benefit of salidroside on colonic inflammation and Th17/Treg adaptive immunity, but transplanting salidroside‐treated foecal bacterium into flora‐depleted wild mice reproduced the resistance of salidroside to gut inflammation. Taken together, our data demonstrated that salidroside protected experimental colitis via skewing macrophage pyroptosis and Th17/Treg balance, indicating its potential effect on UC and other immune disorders.</description><subject>Adaptive immunity</subject><subject>Animals</subject><subject>Bone marrow</subject><subject>Caspase</subject><subject>Colitis - chemically induced</subject><subject>Colitis, Ulcerative - chemically induced</subject><subject>Colitis, Ulcerative - drug therapy</subject><subject>Dextran Sulfate - adverse effects</subject><subject>Digestive system</subject><subject>Dysbacteriosis</subject><subject>Dysbiosis</subject><subject>Flora</subject><subject>Gastrointestinal tract</subject><subject>gut microbiota</subject><subject>Helper cells</subject><subject>IBD</subject><subject>Immune clearance</subject><subject>Immunity</subject><subject>Inflammation - metabolism</subject><subject>Inflammatory bowel disease</subject><subject>Inflammatory bowel diseases</subject><subject>Innate immunity</subject><subject>Intestinal microflora</subject><subject>Lymphocytes T</subject><subject>Macrophages</subject><subject>Macrophages - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mucosal immunity</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</subject><subject>Proteins</subject><subject>Pyroptosis</subject><subject>Salidroside</subject><subject>T-Lymphocytes, Regulatory - metabolism</subject><subject>TREM1 signalling</subject><subject>Triggering Receptor Expressed on Myeloid Cells-1 - metabolism</subject><subject>Ulcerative colitis</subject><issn>0951-418X</issn><issn>1099-1573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kdtKHTEUhkOp1O0B-gQl0BtvRnOYmcxcitRaEBTdgnfDmmTN3pHMocmMZd_1EXxGn8RMPRQEr5KQL1_WWj8hXzk75IyJo2H0hyqX-Sey4KwsE54p-ZksWJnxJOXF7TbZCeGOMVYKln4h2zKXMj4sF-ThGpw1vg_WIAXn8N7CiIFOTqOH0d4j1b2zow003lDbrW0dT92KtqB9P6xhhXTYxN0YHYFCZ6jHAayfmXGN1GxCDXpEb2fg8e8DhNDr-RdDl2uujpYeV9S2NTjoNO6RrQZcwP2XdZfcnP5Ynpwl5xc_f50cnyc65Vme6Dr2lUotUCA0AAXjJm8gVYwpjjozPEtL2fCiyJioGWiTi7qoURTaaF0UcpccPHsH3_-eMIxVa4NGF4vAfgqVUFJkUmV5HtHv79C7fvJdrC5SSjEpuBT_hXEsIXhsqsHbFvym4qyaU6piStWcUkS_vQinukXzBr7GEoHkGfhjHW4-FFWXy6t_wieRlZ_-</recordid><startdate>202302</startdate><enddate>202302</enddate><creator>Liu, Xiaoman</creator><creator>Zhou, Mingxia</creator><creator>Dai, Zhenzhen</creator><creator>Luo, Shangjian</creator><creator>Shi, Yingying</creator><creator>He, Zhenjuan</creator><creator>Chen, Yingwei</creator><general>John Wiley & Sons, Ltd</general><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2371-4570</orcidid></search><sort><creationdate>202302</creationdate><title>Salidroside alleviates ulcerative colitis via inhibiting macrophage pyroptosis and repairing the dysbacteriosis‐associated Th17/Treg imbalance</title><author>Liu, Xiaoman ; Zhou, Mingxia ; Dai, Zhenzhen ; Luo, Shangjian ; Shi, Yingying ; He, Zhenjuan ; Chen, Yingwei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4156-cb41843c2e2eafaa801d6fa470071ec5d15493f188502b0acd62b8be28cdcc883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Adaptive immunity</topic><topic>Animals</topic><topic>Bone marrow</topic><topic>Caspase</topic><topic>Colitis - chemically induced</topic><topic>Colitis, Ulcerative - chemically induced</topic><topic>Colitis, Ulcerative - drug therapy</topic><topic>Dextran Sulfate - adverse effects</topic><topic>Digestive system</topic><topic>Dysbacteriosis</topic><topic>Dysbiosis</topic><topic>Flora</topic><topic>Gastrointestinal tract</topic><topic>gut microbiota</topic><topic>Helper cells</topic><topic>IBD</topic><topic>Immune clearance</topic><topic>Immunity</topic><topic>Inflammation - metabolism</topic><topic>Inflammatory bowel disease</topic><topic>Inflammatory bowel diseases</topic><topic>Innate immunity</topic><topic>Intestinal microflora</topic><topic>Lymphocytes T</topic><topic>Macrophages</topic><topic>Macrophages - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mucosal immunity</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</topic><topic>Proteins</topic><topic>Pyroptosis</topic><topic>Salidroside</topic><topic>T-Lymphocytes, Regulatory - metabolism</topic><topic>TREM1 signalling</topic><topic>Triggering Receptor Expressed on Myeloid Cells-1 - metabolism</topic><topic>Ulcerative colitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Xiaoman</creatorcontrib><creatorcontrib>Zhou, Mingxia</creatorcontrib><creatorcontrib>Dai, Zhenzhen</creatorcontrib><creatorcontrib>Luo, Shangjian</creatorcontrib><creatorcontrib>Shi, Yingying</creatorcontrib><creatorcontrib>He, Zhenjuan</creatorcontrib><creatorcontrib>Chen, Yingwei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Phytotherapy research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Xiaoman</au><au>Zhou, Mingxia</au><au>Dai, Zhenzhen</au><au>Luo, Shangjian</au><au>Shi, Yingying</au><au>He, Zhenjuan</au><au>Chen, Yingwei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Salidroside alleviates ulcerative colitis via inhibiting macrophage pyroptosis and repairing the dysbacteriosis‐associated Th17/Treg imbalance</atitle><jtitle>Phytotherapy research</jtitle><addtitle>Phytother Res</addtitle><date>2023-02</date><risdate>2023</risdate><volume>37</volume><issue>2</issue><spage>367</spage><epage>382</epage><pages>367-382</pages><issn>0951-418X</issn><eissn>1099-1573</eissn><abstract>Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by flora disequilibrium and mucosal immunity disorder. Here, we report that salidroside effectively restricts experimental colitis from two aspects of intestinal macrophage pyroptosis and dysbacteriosis‐derived colonic Th17/Treg imbalance. In innate immunity, the upregulated TREM1 and pyroptosis‐related proteins in inflamed colons were inhibited by salidroside administration and further experiments in vitro showed that salidroside suppressed LPS/ATP‐induced bone marrow‐derived macrophages (BMDMs) pyroptosis evident by the decline of LDH and IL‐1β release as well as the protein level of NLRP3, caspase‐1, and GSDMD p30. Moreover, the TREM1 inhibitor weakened the effect of salidroside on BMDMs pyroptosis, whereas salidroside still could downregulate TREM1 when NLRP3 was inhibited. In adaptive immunity, salidroside improved the gut microflora diversity and Th17/Treg ratio in DSS‐induced mice, especially promoting the abundance of Firmicutes. Clearance of the gut flora blocked the benefit of salidroside on colonic inflammation and Th17/Treg adaptive immunity, but transplanting salidroside‐treated foecal bacterium into flora‐depleted wild mice reproduced the resistance of salidroside to gut inflammation. Taken together, our data demonstrated that salidroside protected experimental colitis via skewing macrophage pyroptosis and Th17/Treg balance, indicating its potential effect on UC and other immune disorders.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>36331009</pmid><doi>10.1002/ptr.7636</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-2371-4570</orcidid></addata></record> |
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| subjects | Adaptive immunity Animals Bone marrow Caspase Colitis - chemically induced Colitis, Ulcerative - chemically induced Colitis, Ulcerative - drug therapy Dextran Sulfate - adverse effects Digestive system Dysbacteriosis Dysbiosis Flora Gastrointestinal tract gut microbiota Helper cells IBD Immune clearance Immunity Inflammation - metabolism Inflammatory bowel disease Inflammatory bowel diseases Innate immunity Intestinal microflora Lymphocytes T Macrophages Macrophages - metabolism Mice Mice, Inbred C57BL Mucosal immunity NLR Family, Pyrin Domain-Containing 3 Protein - metabolism Proteins Pyroptosis Salidroside T-Lymphocytes, Regulatory - metabolism TREM1 signalling Triggering Receptor Expressed on Myeloid Cells-1 - metabolism Ulcerative colitis |
| title | Salidroside alleviates ulcerative colitis via inhibiting macrophage pyroptosis and repairing the dysbacteriosis‐associated Th17/Treg imbalance |
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