ReferenceID 6124

Rutin prevents inflammation-associated colon damage via inhibiting the p38/MAPKAPK2 and PI3K/Akt/GSK3β/NF-κB signalling axes and enhancing splenic Tregs in DSS-induced murine chronic colitis

Food Funct

A large body of emerging evidence has revealed the role of p38/MK2 and PI3K/Akt/GSK3beta cascades in the orchestrating process of colitis. Rutin, a bioflavonoid present in many fruits and vegetables, has been recognized

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Reference Id
6124
Evidence Id
22714
Core Evidence Id
22714
Source Reference Id
5513
Herb2 Reference Id
HBREF006310
Subject Paper Key
HBIN041663_34302158
Pubmed Id
34302158
Doi
10.1039/d1fo01557e
Paper Title
Rutin prevents inflammation-associated colon damage via inhibiting the p38/MAPKAPK2 and PI3K/Akt/GSK3β/NF-κB signalling axes and enhancing splenic Tregs in DSS-induced murine chronic colitis
Paper Abstract
A large body of emerging evidence has revealed the role of p38/MK2 and PI3K/Akt/GSK3beta cascades in the orchestrating process of colitis. Rutin, a bioflavonoid present in many fruits and vegetables, has been recognized to offer therapeutic attributes in acute colitis. However, its role in chronic colitic condition has not yet been delineated in reference to p38/MK2 and PI3K/Akt/GSK3beta signalling. The present investigation assessed the efficacy and underlying molecular mechanism of rutin in alleviating DSS-induced chronic colitis. The analysis of signalling pathways demonstrated the robust activation of PI3K/Akt/GSK3beta/MAPKs/NF-kappaB and p38/MK2 in DSS-induced colitis in animals, which was efficiently alleviated following the rutin treatment. In silico studies indicated its target specificity with these pathways. Rutin administration markedly improved the disease activity score, colon length, goblet cell loss and compromised colon epithelial integrity in colitic mice. Decreased expression of oxi-inflammatory markers such as IgM, IgE, iNOS, ICAM-1, HO-1 and Th1/IL-10 cytokines ratios after treatment suggests its efficacy in regulating effector, regulatory and B cell homeostasis. Additionally, rutin demonstrated its role in restoring epithelial integrity by modulating the transcript levels of tight junction proteins, mucus-secreting proteins, epithelial cell proliferation and apoptosis. Treg expansion revealed that rutin supplementation also exhibits an immune regulatory potential and suppresses inflammatory aggravation mediated by adaptive immune responses. Overall, results indicate that the modulation of p38/MK2 and PI3K/Akt/GSK3beta/NF-kappaB pathways by rutin represents a novel therapeutic approach in chronic colitis that help to curb dysregulated intestinal integrity, cytokine ratio and splenic Tregs.
Journal
Food Funct
Publish Year
2021
Experiment Subject
mouse
Experiment Type
Cell Experiment
Phenotype Related
Chronic Colitic Condition; Colitic; Colitis; Acute Colitis; Chronic Colitis
Paper Title Cn
Paper Title En
Rutin prevents inflammation-associated colon damage via inhibiting the p38/MAPKAPK2 and PI3K/Akt/GSK3β/NF-κB signalling axes and enhancing splenic Tregs in DSS-induced murine chronic colitis
Bilingual Status
semi_complete