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Berberis lycium fruit extract attenuates oxi-inflammatory stress and promotes mucosal healing by mitigating NF-κB/c-Jun/MAPKs signalling and augmenting splenic Treg proliferation in a murine model of dextran sulphate sodium-induced ulcerative colitis

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Abstract

Purpose

There is a growing interest in developing phytomolecule-based therapies for the management of inflammatory disorders owing to rising cost of treatments and unwarranted effects. The present work attempted to assess the efficacy and mechanisms of Berberis lycium Royle fruit extract (BLFE) in mitigating chemical-induced colitis in mice.

Methods

Colitis was induced in Balb/C mice using dextran sulphate sodium (DSS) and protective effects of BLFE were examined. Several oxi-inflammatory parameters, histopathological changes, epithelial barrier integrity and activation of NF-κB/c-Jun/MAPKs in colon tissue were determined. Splenic T cell subpopulations were also gauged to evaluate the systemic effects of BLFE in the modulation of immune responses.

Results

BLFE treatment effectively improved animal survival rate, DAI score, colon length and structural damage in DSS-exposed mice. Expression of oxi-inflammatory markers such as MPO, IgE, iNOS, ICAM-1, MCP-1 and RANTES as well as Th1/Th2/Th17 cytokines were decreased in BLFE treated animals. On the other hand, an increased mRNA expression of anti-inflammatory cytokines (IL-4/IL-10), tight junction proteins and IgA levels were also observed during BLFE treatment. BLFE appeared to modulate intestinal epithelial cell proliferation (PCNA) and apoptosis (Bcl2/Bax), thereby suggesting its role in the maintenance of intestinal integrity. Analysis of inflammatory signalling pathways indicated robust activation and expression of NF-κB/c-Jun/MAPKs (JNK and p38) in DSS treated animal which was strongly abrogated by BLFE treatment. BLFE supplementation also enhanced the proliferation of CD3+CD4+CD25+ Treg cells indicating suppression of inflammatory activation.

Conclusion

These observations provide compelling evidence that BLFE could be considered as a viable natural strategy in the prevention and management of ulcerative colitis.

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Acknowledgements

We express our gratitude to the Director, CSIR- IHBT Palampur, for his support and encouragement. We acknowledge SEED, Department of Science and Technology, for providing financial assistance through project GAP-0193 and CSIR for project MLP-0204, respectively, along with Academy of Scientific and Innovative Research (AcSIR), New Delhi, India for Ph.D. registration. CSIR-IHBT communication number for this manuscript is: 4386.

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Authors and Affiliations

  1. Pharmacology and Toxicology Lab, Food and Nutraceutical Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, HP, 176061, India

    Anamika Sharma, Narendra Vijay Tirpude, Pankaj Markand Kulurkar, Rohit Sharma & Yogendra Padwad

  2. Academy of Scientific and Innovative Research, CSIR-Institute of Himalayan Bioresource Technology, Palampur, HP, India

    Anamika Sharma, Narendra Vijay Tirpude, Rohit Sharma & Yogendra Padwad

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Contributions

AS and YS conceptualized and designed the study. AS and NT developed animal model and performed experiments. NT was involved in data analysis of histopathology, immunofluorescence and immunohistochemistry. AS and PK performed haematology and biochemistry analysis. AS analysed the data. AS, NT and YP wrote the manuscript. YP and RS edited and revised the manuscript. All authors corrected and approved the manuscript.

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Correspondence to Yogendra Padwad.

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Sharma, A., Tirpude, N.V., Kulurkar, P.M. et al. Berberis lycium fruit extract attenuates oxi-inflammatory stress and promotes mucosal healing by mitigating NF-κB/c-Jun/MAPKs signalling and augmenting splenic Treg proliferation in a murine model of dextran sulphate sodium-induced ulcerative colitis. Eur J Nutr 59, 2663–2681 (2020). https://doi.org/10.1007/s00394-019-02114-1

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