HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Canthin-6-one ameliorates TNBS-induced colitis in rats by modulating inflammation and oxidative stress. An in vivo and in silico approach.

Abstract
Canthin-6-one (Cant) is an indole alkaloid found in several botanical drugs used as medicines, reported to be gastroprotective, anti-inflammatory, anti-microbial, anti-diarrheal and anti-proliferative. We aimed to explore Cant in the management of colitis using a trinitrobenzenesulfonic acid (TNBS)-induced rat model. Cant (1, 5 and 25 mg/kg) was administered by oral gavage to Wistar rats followed by induction of colitis with TNBS. Macroscopic and histopathological scores, myeloperoxidase (MPO), malondialdehyde (MDA) and reduced glutathione (GSH) were assessed in colon tissues. Pro- (TNF-α, IL-1β and IL-12p70) and anti-inflammatory (IL-10) cytokines, and vascular endothelial growth factor (VEGF) were also quantified. Mitogen-activated protein kinase 14 (MAPK14) and Toll-like receptor-8 (TLR8), as putative targets, were considered through in silico analysis. Cant (5 and 25 mg/kg) reduced macroscopic and histological colon damage scores in TNBS-treated rats. MPO and MDA were reduced by up to 61.69% and 92.45%, respectively, compared to TNBS-treated rats alone. Glutathione concentration was reduced in rats administered with TNBS alone (50.00% of sham group) but restored to 72.73% (of sham group) with Cant treatment. TNF-α, IL-1β, IL-12p70 and VEGF were reduced, and anti-inflammatory IL-10 was increased following Cant administration compared to rats administered TNBS alone. Docking ligation results for MAPK14 (p38α) and TLR8 with Cant, confirmed that these proteins are feasible putative targets. Cant has an anti-inflammatory effect in the intestine by down-regulating molecular immune mediators and decreasing oxidative stress. Therefore, Cant could have therapeutic potential for the treatment of inflammatory bowel disease and related syndromes.
AuthorsKaruppusamy Arunachalam, Amilcar Sabino Damazo, Antonio Macho, Monica Steffi Matchado, Eduarda Pavan, Fabiana de Freitas Figueiredo, Darley Maria Oliveira, Carrie A Duckworth, Parimelazhagan Thangaraj, Marco Leonti, Domingos Tabajara de Oliveira Martins
JournalBiochemical pharmacology (Biochem Pharmacol) Vol. 186 Pg. 114490 (04 2021) ISSN: 1873-2968 [Electronic] England
PMID33647259 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2021 Elsevier Inc. All rights reserved.
Chemical References
  • Anti-Inflammatory Agents
  • Carbolines
  • Fungicides, Industrial
  • Indole Alkaloids
  • Inflammation Mediators
  • canthin-6-one
  • Trinitrobenzenesulfonic Acid
Topics
  • Animals
  • Anti-Inflammatory Agents (chemistry, pharmacology, therapeutic use)
  • Carbolines (chemistry, pharmacology, therapeutic use)
  • Colitis (chemically induced, drug therapy, metabolism)
  • Computer Simulation
  • Fungicides, Industrial (chemistry, pharmacology, therapeutic use)
  • Indole Alkaloids (chemistry, pharmacology, therapeutic use)
  • Inflammation (chemically induced, drug therapy, metabolism)
  • Inflammation Mediators (antagonists & inhibitors, metabolism)
  • Male
  • Oxidative Stress (drug effects, physiology)
  • Protein Structure, Secondary
  • Rats
  • Rats, Wistar
  • Trinitrobenzenesulfonic Acid (toxicity)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: