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Sinigrin Attenuates the Dextran Sulfate Sodium-induced Colitis in Mice by Modulating the MAPK Pathway

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Abstract

Ulcerative colitis (UC) is an intestinal inflammatory disease characterised by the loss of intestinal crypts, edema, mucosal ulceration, and infiltration of inflammatory cells in the mucosa. The current study aimed to investigate the protective and therapeutic effects of sinigrin and underlying mechanisms in a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis. DSS-induced colitis models were used to demonstrate sinigrin’s therapeutic/protective action. Mice were orally administered with sinigrin (15 mg/kg or 30 mg/kg) for a period of 12 days in both prophylactic and therapeutic models. Animal weights, stool consistency, and bleeding parameters were measured throughout the experimental period. After the experimental period, colon lengths were measured, and colon tissues were harvested to determine the levels of oxidative stress–inducing factors (nitrates and MDA levels) and anti-oxidant components (GSH, SOD, and catalase). Furthermore, gene expression analysis, IL-17 levels, and inflammatory marker expressions were measured using RT-qPCR, ELISA, and immunohistochemical methods respectively. Furthermore, histopathological observations and elucidation of the mechanism of action were determined using H&E analysis and Western blot analysis. Sinigrin treatment (in both prophylactic and therapeutic models) significantly mitigated the DSS-induced body weight loss, attenuated the colon length shrinkage, and improved the disease index score (p < 0.001). Further results revealed that sinigrin’s protective/therapeutic effect is associated with a significant attenuation of pro‑inflammatory cytokine production (p < 0.001), reversing the anti-oxidant enzyme levels (p < 0.001) and substantial improvement (2 folds) of the disruption of the colonic morphology in colon tissues compared to DSS control. Immunohistochemical analysis showed that sinigrin treatment remarkably reduced the DSS-induced myeloperoxidase, neutrophil elastase, and CD68 expression in colon tissues. Additionally, sinigrin successfully abrogated the DSS-induced IL-17 levels (p < 0.001) and improved the colonic barrier in colon tissues. Overall, these results demonstrated that sinigrin exerts protective and therapeutic effects on DSS‑induced colitis, by enhancing the anti-oxidant enzymes and suppressing the intestinal inflammatory cascade of markers by regulating the MAPK pathway.

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Data Availability

All data generated or analysed during this study are included in this manuscript file (and its supplementary information files).

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Acknowledgements

Authors thank the Director, CSIR-IICT, Hyderabad, India, for providing the facilities and funding necessary for the conducting of this work. CSIR-IICT manuscript communication number: IICT/Pubs./2022/214.

Funding

Used internal funds of the institute. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

All data generated or analyzed during this study are included in this manuscript file (and its supplementary information files).

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Authors and Affiliations

  1. Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad-500 007, Hyderabad, Telangana, India

    Rama Satya Sri Kotipalli, Satya Krishna Tirunavalli, Madhusudhana Kuncha, Ramakrishna Sistla & Sai Balaji Andugulapati

  2. Academy of Scientific and Innovative Research (AcSIR), Uttar Pradesh- 201 002, Ghaziabad, India

    Rama Satya Sri Kotipalli, Satya Krishna Tirunavalli, Ramakrishna Sistla & Sai Balaji Andugulapati

  3. Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, PIN-781101, Changsari, Assam, India

    Aniket Balasaheb Pote & Bidya Dhar Sahu

  4. Centre for Cellular and Molecular Biology, 500 007, Hyderabad, Telangana, India

    Mahesh Kumar Jerald

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Contributions

Conceptualization: S.R.K, S.B.A, methodology: R. S.K, S.K.T, A.S.B, B.D.S; Western blot analysis and immunohistochemistry: S.K.T, anti-oxidant assays: R.S.K, In vivo experiments: M.K, R.S.K, A.B.P, histopathology: M.K.J, A.S.B; manuscript writing—review and editing: S.B.A, and S. R. K.; funding acquisition: S.R. K.

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Correspondence to Sai Balaji Andugulapati.

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Kotipalli, R.S.S., Tirunavalli, S.K., Pote, A.B. et al. Sinigrin Attenuates the Dextran Sulfate Sodium-induced Colitis in Mice by Modulating the MAPK Pathway. Inflammation 46, 787–807 (2023). https://doi.org/10.1007/s10753-022-01780-4

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