Volume 14 Issue 2
Feb.  2024
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Haochen Hui, Zhuoya Wang, Xuerong Zhao, Lina Xu, Lianhong Yin, Feifei Wang, Liping Qu, Jinyong Peng. Gut microbiome-based thiamine metabolism contributes to the protective effect of one acidic polysaccharide from Selaginella uncinata (Desv.) Spring against inflammatory bowel disease[J]. Journal of Pharmaceutical Analysis, 2024, 14(2): 177-195. doi: 10.1016/j.jpha.2023.08.003
Citation: Haochen Hui, Zhuoya Wang, Xuerong Zhao, Lina Xu, Lianhong Yin, Feifei Wang, Liping Qu, Jinyong Peng. Gut microbiome-based thiamine metabolism contributes to the protective effect of one acidic polysaccharide from Selaginella uncinata (Desv.) Spring against inflammatory bowel disease[J]. Journal of Pharmaceutical Analysis, 2024, 14(2): 177-195. doi: 10.1016/j.jpha.2023.08.003

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

doi: 10.1016/j.jpha.2023.08.003
Funds:

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

  • Received Date: Apr. 16, 2023
  • Accepted Date: Aug. 07, 2023
  • Rev Recd Date: Jul. 28, 2023
  • Available Online: Mar. 08, 2024
  • Publish Date: Feb. 29, 2024
  • 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.
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