Visnagin attenuates acute pancreatitis via Nrf2/NFκB pathway and abrogates associated multiple organ dysfunction.

Autor: Pasari LP; Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana State, India., Khurana A; Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana State, India., Anchi P; Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana State, India., Aslam Saifi M; Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana State, India., Annaldas S; Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana State, India., Godugu C; Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana State, India. Electronic address: chandra.niperhyd@gov.in.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2019 Apr; Vol. 112, pp. 108629. Date of Electronic Publication: 2019 Feb 22.
DOI: 10.1016/j.biopha.2019.108629
Abstrakt: Acute pancreatitis (AP) is an exocrine dysfunction of the pancreas where oxidative stress and inflammatory cytokines play a key role in induction and progression of the disease. Studies have demonstrated that antioxidant phytochemicals have been effective in improving pancreatitis condition, but there are no clinically approved drugs till date. Our study aims to assess the preventive activity of visnagin, a novel phytochemical isolated from Ammi visnaga against cerulein induced AP. Male Swiss albino mice were divided into six groups (n = 6, each group) comprising of normal control, cerulein control, seven day pre-treatment with visnagin at three dose levels; visnagin low dose (10 mg/kg), visnagin mid dose (30 mg/kg), visnagin high dose (60 mg/kg) and visnagin control (60 mg/kg). AP was induced by six injections of cerulein (50 μg/kg, i.p.) on the 7 th day and the animals were sacrificed after 6 h of last cerulein dose. Various markers of pancreatic function, oxidative stress and inflammation were assessed. Visnagin was found to be effective in reducing plasma amylase and lipase levels, reduced cerulein induced oxidative stress. Visnagin dose dependently decreased the expression of IL-1β, IL-6, TNF-α and IL-17. It attenuated the levels of nuclear p65-NFκB. Visnagin improved the antioxidant defence by improving Nrf2 expression and halted pancreatic inflammation by suppressing NFκB and nitrotyrosine expression in the acinar cells. Further, it attenuated the expression of markers of multiple organ dysfunction syndrome and reduced inflammatory cytokines in lungs and intestine. Cumulatively, these findings indicate that visnagin has substantial potential to prevent cerulein induced AP.
(Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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