Diosmin alleviates ulcerative colitis in mice by increasing Akkermansia muciniphila abundance, improving intestinal barrier function, and modulating the NF-κB and Nrf2 pathways

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Salem M.B.; El-Lakkany N.M.; Seif el-Din S.H.; Hammam O.A.; Samir S.

Journal: Heliyon

Publisher: Elsevier Ltd

Publication Date: March 2024

Volume / Issue: Volume 10 / Issue 6

Article No.: e27527

ISSN: 24058440

DOI: 10.1016/j.heliyon.2024.e27527

Scopus: View on Scopus

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Salem M.B., Department of Pharmacology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; El-Lakkany N.M., Department of Pharmacology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; Seif el-Din S.H., Department of Pharmacology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; Hammam O.A., Department of Pathology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; Samir S., Department of Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt

Abstract

Ulcerative colitis is a common type of inflammatory bowel disease that affects millions of individuals around the world. Traditional UC treatment has focused on suppressing immune responses rather than treating the underlying causes of UC, which include oxidative stress, inflammation, and microbiota dysbiosis. Diosmin (DIO), a naturally occurring flavonoid, possesses antioxidant and anti-inflammatory properties. This study aimed to assess the efficacy of DIO in treating dextran-sulfate sodium (DSS)-induced colitis, and to investigate some of its underlying mechanisms, with an emphasis on Akkermansia muciniphila abundance, inflammatory markers, and intestinal barrier function. C57BL/6 mice were given 4% (w/v) DSS to induce colitis. DSS-induced mice were administered DIO (100 and 200 mg/kg) or sulfasalazine orally for 7 days. Every day, the disease activity index (DAI) was determined by recording body weight, diarrhea, and bloody stool. Changes in fecal A. muciniphila abundance, colonic MUC1 and MUC2 expression, as well as oxidative stress and inflammatory markers were all assessed. Histopathological changes, colonic PIK3PR3 and ZO-1 levels, and immunohistochemical examinations of occludin and claudin-1, were investigated. DIO administration resulted in a dose-dependent decrease in DAI, as well as increase in A. muciniphila abundance and MUC2 expression while decreasing MUC1 expression. DIO also dramatically reduced colonic oxidative stress and inflammation by regulating the NF-κB and Nrf2 cascades, restored intestinal barrier integrity by inhibiting PIK3R3 and inducing ZO-1, and improved occludin/claudin-1 gene expression and immunostaining. This study provides the first evidence that DIO preserves intestinal barrier integrity and increases A. muciniphila abundance in DSS-induced colitis. However, more research is required to explore the impact of DIO on the overall composition and diversity of the gut microbiota. Likewise, it will be important to fully understand the molecular mechanisms by which A. muciniphila maintains intestinal barrier function and its potential use as an adjuvant in the treatment of UC. © 2024 The Authors

Keywords

Akkermansia muciniphila; Diosmin; Inflammation; Intestinal barrier integrity; Oxidative stress; Ulcerative colitis

Citation Information

Scopus Citations: 32

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