Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2018; 24(16): 1679-1707
Published online Apr 28, 2018. doi: 10.3748/wjg.v24.i16.1679
Beneficial effects of naringenin in liver diseases: Molecular mechanisms
Erika Hernández-Aquino, Pablo Muriel
Erika Hernández-Aquino, Pablo Muriel, Laboratory of Experimental Hepatology, Department of Pharmacology, Cinvestav-IPN, Mexico City 07000, Mexico
Author contributions: All authors equally contributed to this paper with the conception and design of the study, the literature review and analysis, the drafting and critical revision and editing of the manuscript, and with their final approval of the final version.
Supported by National Council of Science and Technology (Conacyt) of Mexico, No. 253037.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Pablo Muriel, PhD, Research Scientist, Laboratory of Experimental Hepatology, Department of Pharmacology, Cinvestav-IPN, Av. Instituto Politécnico Nacional 2508, Apartado postal 14-740, Mexico City 07000, Mexico.
Telephone: +52-55-57473303 Fax: +52-55-57473394
Received: March 7, 2018
Peer-review started: March 8, 2018
First decision: March 29, 2018
Revised: April 4, 2018
Accepted: April 16, 2018
Article in press: April 16, 2018
Published online: April 28, 2018

Liver diseases are caused by different etiological agents, mainly alcohol consumption, viruses, drug intoxication or malnutrition. Frequently, liver diseases are initiated by oxidative stress and inflammation that lead to the excessive production of extracellular matrix (ECM), followed by a progression to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). It has been reported that some natural products display hepatoprotective properties. Naringenin is a flavonoid with antioxidant, antifibrogenic, anti-inflammatory and anticancer properties that is capable of preventing liver damage caused by different agents. The main protective effects of naringenin in liver diseases are the inhibition of oxidative stress, transforming growth factor (TGF-β) pathway and the prevention of the transdifferentiation of hepatic stellate cells (HSC), leading to decreased collagen synthesis. Other effects include the inhibition of the mitogen activated protein kinase (MAPK), toll-like receptor (TLR) and TGF-β non-canonical pathways, the inhibition of which further results in a strong reduction in ECM synthesis and deposition. In addition, naringenin has shown beneficial effects on nonalcoholic fatty liver disease (NAFLD) through the regulation of lipid metabolism, modulating the synthesis and oxidation of lipids and cholesterol. Moreover, naringenin protects from HCC, since it inhibits growth factors such as TGF-β and vascular endothelial growth factor (VEGF), inducing apoptosis and regulating MAPK pathways. Naringenin is safe and acts by targeting multiple proteins. However, it possesses low bioavailability and high intestinal metabolism. In this regard, formulations, such as nanoparticles or liposomes, have been developed to improve naringenin bioavailability. We conclude that naringenin should be considered in the future as an important candidate in the treatment of different liver diseases.

Keywords: Naringenin, Transforming growth factor, Liver, Fibrosis, MAPKs, CCl4, Flavonoids, JNK, Hepatic stellate cells, Cirrhosis, Smads, α-SMA

Core tip: Natural products such as flavonoids have been shown to display hepatoprotective properties. Naringenin possesses the ability to inhibit oxidative stress and inflammation and has anti-inflammatory and anticancer properties. Thus, naringenin should be considered in the future as an important candidate for the treatment of liver diseases.