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. 2024 Dec 21;22(12):573.
doi: 10.3390/md22120573.

Lithium Coupled with C6-Carboxyl Improves the Efficacy of Oligoguluronate in DSS-Induced Ulcerative Colitis in C57BL/6J Mice

Jiayi Li  1 , Meng Shao  2 , Hao Liu  2 , Peng Guo  2 , Fei Liu  2 , Mingfeng Ma  1 , Quancai Li  1   2
Affiliations

Lithium Coupled with C6-Carboxyl Improves the Efficacy of Oligoguluronate in DSS-Induced Ulcerative Colitis in C57BL/6J Mice

Jiayi Li et al. Mar Drugs. .

Abstract

Oligoguluronate lithium (OGLi) was prepared for the purpose of enhancing the anti-ulcerative colitis (UC) activities of OG, in which lithium (Li+) is coupled with the C6-carboxyl of G residue. The therapeutic effects of OGLi on dextran sulfate (DSS)-induced UC mice were investigated, and oligoguluronate sodium (OGNa) and lithium carbonate (LC) were used as contrasts. The effects of OGLi, OGNa and LC on the treatment of UC mice were studied by monitoring body weight change and evaluating colon length, the disease activity index (DAI), histopathological examination and gut microbiota regulation. The results showed that compared with OGNa and LC, OGLi significantly reduced the clinical symptoms and histopathological changes associated with UC in the acute model. It was worth noting that OGLi significantly changed the gut microbiota characteristics of the DSS-treated mice and corrected the typical dysbacteriosis of DSS-induced UC. This intervention resulted in increasing the abundance of norank_f_Muribaculaceae and Ileibacterium spp. while reducing the levels of Escherichia-Shigella spp. and Romboutsia spp. The OGLi could significantly increase the diversity of intestinal microorganisms in the short term. All of these discoveries demonstrate that lithium collaboratively enhances the anti-UC efficacy of OG, which will help to create OG-based drugs for the treatment of UC.

Keywords: collaborative efficacy enhancement; gut microbiota; lithium; oligoguluronate; ulcerative colitis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The preparation process of OGLi.
Figure 2
Figure 2
Characteristic analysis of OGLi. (A) UV–Vis spectrum. (B) FT–IR spectrum. (C) 1H–NMR spectrum. (D) HPGPC chromatogram.
Figure 3
Figure 3
The effects of the oral administration of OGLi, OGNa and LC on DSS-induced UC in mice. (A) A graphical illustration of the experimental design. (B) Body weight changes of the mice. (C) Representative images of the colon. (D) The quantitative analysis of colon length. (E) The DAI analysis of UC. * p < 0.05 versus NC group; ** p < 0.01 versus NC group; *** p < 0.001 versus NC group; # p < 0.05 versus MD group; ## p < 0.01 versus MD group.
Figure 4
Figure 4
The effects of the oral administration of OGLi, OGNa and LC on DSS–induced mucosal damage in the colon. (A) H&E staining. (B) Colon score analysis based on H&E staining. ** p < 0.01 versus NC group; *** p < 0.001 versus NC group; ### p < 0.001 versus MD group.
Figure 5
Figure 5
The effects of the oral administration of OGLi, OGNa and LC on the composition of gut microbiota in mice. (A) A Venn diagram analysis of the OTUs. (B) NMDS score plot analysis. (C) The Shannon index of gut microbial diversity and abundance. (D) The Chao index of gut microbial diversity and abundance. (E) The LEfSe LDA score analysis of the gut microbiota between the five groups. * p < 0.05 versus NC group; # p < 0.01 versus MD group; ## p < 0.001 versus MD group.
Figure 6
Figure 6
The effects of the oral administration of OGLi, OGNa and LC on statistically significant differences (p < 0.05) in the abundance of gut microbiota at the genus level. (A) The taxa with significant differences in abundance at the genus level between MD versus NC. (B) MD versus OGLi. (C) MD versus OGNa. (D) MD versus LC.
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