Narirutin mitigates dextrose sodium sulfate-induced colitis in mice by modulating intestinal flora

Dianwen Xu; Dianfeng Liu; Naiyuan Jiang; Yachun Xie; Dewei He; Ji Cheng; Juxiong Liu; Shoupeng Fu; Guiqiu Hu

doi:10.1016/j.phymed.2024.155730

Narirutin mitigates dextrose sodium sulfate-induced colitis in mice by modulating intestinal flora

Phytomedicine. 2024 May 10:130:155730. doi: 10.1016/j.phymed.2024.155730. Online ahead of print.

Authors

Dianwen Xu¹, Dianfeng Liu², Naiyuan Jiang³, Yachun Xie¹, Dewei He², Ji Cheng¹, Juxiong Liu¹, Shoupeng Fu⁴, Guiqiu Hu⁵

Affiliations

¹ State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China.
² College of Animal Science, Jilin University, Changchun, China.
³ College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China.
⁴ State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China. Electronic address: fushoupeng@jlu.edu.cn.
⁵ State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China. Electronic address: huguiqiu@jlu.edu.cn.

PMID: 38759313
DOI: 10.1016/j.phymed.2024.155730

Abstract

Background: Ulcerative colitis (UC) is a prolonged inflammatory disease of the gastrointestinal tract. Current therapeutic options remain limited, underscoring the imperative to explore novel therapeutic strategies. Narirutin (NR), a flavonoid naturally present in citrus fruits, exhibits excellent anti-inflammatory effects in vitro, yet its in vivo efficacy, especially in UC, remains underexplored.

Objective: This work examined the effect of NR on dextrose sodium sulfate (DSS)-induced UC in mice in vivo, with a specific focus on the role of gut flora in it.

Methods: The effects of NR (10, 20, and 40 mg/kg) on DSS-induced UC in mice were investigated by monitoring changes in body weight, disease activity index (DAI) scores, colon length, and histological damage. Colonic levels of pro-inflammatory mediators, tight junction (TJ) proteins, and inflammation-related signaling pathway proteins were analyzed via enzyme-linked immunosorbent assay, western blot, and immunofluorescence. The role of gut microbiota in NR against colitis was analyzed through 16S rRNA sequencing, flora clearance assays, and fecal microbiota transplantation (FMT) assays.

Results: NR administration suppressed DSS-induced colitis as reflected in a decrease in body weight loss, DAI score, colon length shortening, and histological score. Furthermore, NR administration preserved the integrity of the DSS-induced intestinal barrier by inhibiting the reduction of TJ proteins (claudin3, occludin, and zonula occludens-1). Moreover, NR administration markedly repressed the activation of the toll-like receptor 4-mitogen-activated protein kinase/nuclear factor-κB pathway and reduced the amount of pro-inflammatory mediators in the colon. Importantly, the results of 16S rRNA sequencing showed that the intestinal flora of mice with colitis exhibited richer microbial diversity following NR administration, with elevated abundance of Lactobacillaceae (Lactobacillus) and decreased abundance of Bacteroidaceae (Bacteroides) and Shigella. In addition, the anti-colitis effect of NR almost disappeared after gut flora clearance. Further FMT assay also validated this gut flora-dependent protective mechanism of NR.

Conclusion: Our findings suggest that NR is a prospective natural compound for the management of UC by modulating intestinal flora.

Keywords: Fecal microbiota transplantation; Gut microbiota; Inflammation; Narirutin; Ulcerative colitis.