Gut microbiome-based thiamine metabolism contributes to the protective effect of one acidic polysaccharide from Selaginella uncinata(Desv.)Spring against inflammatory bowel disease  

作　　者：Haochen Hui Zhuoya Wang Xuerong Zhao Lina Xu Lianhong Yin Feifei Wang Liping Qu Jinyong Peng 

机构地区：[1]Department of Pharmaceutical Analysis,College of Pharmacy,Dalian Medical University,Dalian,Liaoning,116044,China [2]Innovation Materials Research and Development Center,Botanee Research Institute,Yunnan Botanee Bio-technology Group Co.,Ltd.,Kunming,650106,China [3]Department of Traditional Chinese Medicine Pharmacology,School of Pharmacy,Anhui University of Chinese Medicine,Hefei,230012,China

出　　处：《Journal of Pharmaceutical Analysis》2024年第2期177-195,共19页药物分析学报（英文版）

基　　金：the funding from the Spring City Plan of the High-Level Talent Promotion and Training Project of Kunming,China(Grant No.:2022SCP008);the Independent Research Fund of Yunnan Characteristic Plant Extraction Laboratory,China(Grant No.:2022YKZY001).

摘　　要：Inflammatory bowel disease(IBD)is a serious disorder,and exploration of active compounds to treat it is necessary.An acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata(Desv.)Spring,which contained galacturonic acid,galactose,xylose,arabinose,and rhamnose with the main chain structure of→4)-α-d-GalAp-(1→and→6)-β-d-Galp-(1→and the branched structure of→5)-α-l-Araf-(1→.Animal experiments showed that compared with Model group,SUSP-4 significantly improved body weight status,disease activity index(DAI),colonic shortening,and histopathological damage,and elevated occludin and zonula occludens protein 1(ZO-1)expression in mice induced by dextran sulfate sodium salt(DSS).16S ribosomal RNA(rRNA)sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and Alistipes.Metabolomics results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism,which was further confirmed by a targeted metabolism study.Fecal transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice.A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B(p-NF-κB)and cyclooxygenase-2(COX-2)and elevating NF-E2-related factor 2(Nrf2)levels compared with Model group.In conclusion,SUSP-4 affected thiamine metabolism by regulating Akkermania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against IBD.This is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD,showing great potential for in-depth research and development applications.

关 键 词：Gut microbiota Inflammatory bowel disease POLYSACCHARIDE Selaginella uncinata(Desv.)Spring Thiamine metabolism 

分 类 号：R114[医药卫生—卫生毒理学]