Original Research ARTICLE
Pristimerin as a novel hepatoprotective agent against experimental autoimmune hepatitis
- 1Pharmacology and Toxicology, Taibah University, Saudi Arabia
- 2Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Egypt
- 3Pathology, Taibah University, Saudi Arabia
Pristimerin (Pris) is bioactive natural quinonoid triterpene that has anti-inflammatory and anti-cancer activities. Meanwhile, its effect against hepatitis needs to be elucidated. This investigation aimed to evaluate the ability of Pris to protect against autoimmune hepatitis (AIH). A mouse model of AIH was established using single concanavalin A (Con A) intravenous injection. Mice were treated with Pris at two different doses (0.4 & 0.8 mg/kg) for 5 days prior to Con A challenge. Markers of hepatic injury, oxidative, inflammatory and apoptotic damage were estimated.
Results have revealed that Pris pretreatment ameliorated Con A-induced hepatic damage. There was decrease in the elevated serum indices of hepatic damage (ALT, AST, ALP and LDH) and improvement of the histopathological picture of the liver. Pris effectively decreased Con A-induced neutrophil infiltration into the hepatic tissue as presented by amelioration of the level and immuno-expression of myeloperoxidase (MPO). Additionally, Pris attenuated Con A-induced increase in CD4+ T-cells in hepatic tissue. Lipid peroxidation was significantly depressed simultaneously with enhancement of the antioxidant capacity in Pris pretreated animals. Pris also enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression and its binding capacity. In addition, Pris increased mRNA expression of heme-oxygenase-1 (HO-1) and restored its normal level. Furthermore, Pris decreased the level and immuno-expression of nuclear factor kappa-B (NF-κB) as well as the downstream inflammatory cascade (TNF-α, IL-6 and IL-1β). Finally, Pris showed inhibitory effect on Con A-induced apoptotic alteration in liver as it decreased the mRNA expression and levels the apoptotic markers (Bax and caspase-3) and increased mRNA expression and level of the anti-apoptotic protein (Bcl2).
In conclusion, this study demonstrates the potent hepatoprotective efficacy of Pris against Con A-induced hepatitis which may be related to anti-oxidative, anti-inflammatory and anti-apoptotic pathways. Pris could serve as a new candidate for the management of hepatitis.
Keywords: Pristimerin, Hepatitis, Nuclear factor erythroid-related factor 2 (Nrf2), Hemeoxygenase-1, Nuclear factor kappa-B, Apoptosis
Received: 04 Dec 2017;
Accepted: 13 Mar 2018.
Edited by:Ralf Weiskirchen, RWTH Aachen Universität, Germany
Reviewed by:Martin Roderfeld, Justus Liebig Universität Gießen, Germany
Feng Li, Baylor College of Medicine, United States
Andreas Teufel, Medizinische Fakultät Mannheim, Universität Heidelberg, Germany
Copyright: © 2018 El-Agamy, Shaaban and Elkablawy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Dina S. El-Agamy, Taibah University, Pharmacology and Toxicology, Medina, 30001, Saudi Arabia, firstname.lastname@example.org