PMID- 36331009 OWN - NLM STAT- MEDLINE DCOM- 20230222 LR - 20230222 IS - 1099-1573 (Electronic) IS - 0951-418X (Linking) VI - 37 IP - 2 DP - 2023 Feb TI - Salidroside alleviates ulcerative colitis via inhibiting macrophage pyroptosis and repairing the dysbacteriosis-associated Th17/Treg imbalance. PG - 367-382 LID - 10.1002/ptr.7636 [doi] AB - 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-1beta 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. CI - (c) 2022 John Wiley & Sons Ltd. FAU - Liu, Xiaoman AU - Liu X AUID- ORCID: 0000-0002-2371-4570 AD - Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. AD - Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. FAU - Zhou, Mingxia AU - Zhou M AD - Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. FAU - Dai, Zhenzhen AU - Dai Z AD - Shanghai Institute for Pediatric Research, Shanghai, China. FAU - Luo, Shangjian AU - Luo S AD - Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. AD - Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. FAU - Shi, Yingying AU - Shi Y AD - Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. AD - Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. FAU - He, Zhenjuan AU - He Z AD - Department of Neonatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. FAU - Chen, Yingwei AU - Chen Y AD - Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. LA - eng GR - 8197030824/National Natural Science Foundation of China/ PT - Journal Article DEP - 20221104 PL - England TA - Phytother Res JT - Phytotherapy research : PTR JID - 8904486 RN - M983H6N1S9 (rhodioloside) RN - 0 (Triggering Receptor Expressed on Myeloid Cells-1) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 9042-14-2 (Dextran Sulfate) SB - IM MH - Animals MH - Mice MH - *Colitis, Ulcerative/chemically induced/drug therapy MH - Triggering Receptor Expressed on Myeloid Cells-1/metabolism MH - Pyroptosis MH - T-Lymphocytes, Regulatory/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Dysbiosis MH - *Colitis/chemically induced MH - Macrophages/metabolism MH - Inflammation/metabolism MH - Dextran Sulfate/adverse effects MH - Mice, Inbred C57BL OTO - NOTNLM OT - IBD OT - Salidroside OT - TREM1 signalling OT - gut microbiota OT - pyroptosis EDAT- 2022/11/05 06:00 MHDA- 2023/02/22 06:00 CRDT- 2022/11/04 06:32 PHST- 2022/09/03 00:00 [revised] PHST- 2022/06/16 00:00 [received] PHST- 2022/09/14 00:00 [accepted] PHST- 2022/11/05 06:00 [pubmed] PHST- 2023/02/22 06:00 [medline] PHST- 2022/11/04 06:32 [entrez] AID - 10.1002/ptr.7636 [doi] PST - ppublish SO - Phytother Res. 2023 Feb;37(2):367-382. doi: 10.1002/ptr.7636. Epub 2022 Nov 4.