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.

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 CD3CD4CD25 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.