Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2017; 23(24): 4354-4368
Published online Jun 28, 2017. doi: 10.3748/wjg.v23.i24.4354
Naringenin prevents experimental liver fibrosis by blocking TGFβ-Smad3 and JNK-Smad3 pathways
Erika Hernández-Aquino, Natanael Zarco, Sael Casas-Grajales, Erika Ramos-Tovar, Rosa E Flores-Beltrán, Jonathan Arauz, Mineko Shibayama, Liliana Favari, Víctor Tsutsumi, José Segovia, Pablo Muriel
Erika Hernández-Aquino, Sael Casas-Grajales, Erika Ramos-Tovar, Rosa E Flores-Beltrán, Liliana Favari, Pablo Muriel, Laboratory of Experimental Hepatology, Department of Pharmacology, Cinvestav-IPN, Apartado Postal 14-740, Mexico City, Mexico
Natanael Zarco, José Segovia, Department of Physiology, Biophysics and Neurosciences, Cinvestav-IPN, Apartado Postal 14-740, Mexico City, Mexico
Jonathan Arauz, Department of Pharmacology, School of Medicine, Autonomous University of Baja California, Mexicali, Apartado Postal 21100, Baja California, Mexico
Mineko Shibayama, Víctor Tsutsumi, Department of Infectomics and Molecular Pathogenesis, Cinvestav-IPN, Apartado Postal 14-740, Mexico City, Mexico
Author contributions: Hernández-Aquino E, Zarco N, Casas-Grajales S, Ramos-Tovar E, Flores-Beltrán RE, Arauz J, Favari L and Segovia J performed the biochemical, molecular and zymography determinations; Shibayama M and Tsutsumi V performed the histological stains and their interpretation; and Muriel P designed the research and wrote the paper together with Hernández-Aquino E.
Supported by National Council of Science and Technology (Conacyt) of Mexico, No. 253037 to Muriel P, and No. 239516 to Segovia J; Fellowship No. 358378 Hernández-Aquino E to from Conacyt; This work was also partially supported by a grant of PRODEP (UABC-PTC-464) Mexico.
Institutional animal care and use committee statement: The study complies with the Institution’s guidelines and the Mexican official regulation (NOM-062-ZOO-1999).
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional data are available.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Pablo Muriel, PhD, Laboratory of Experimental Hepatology, Department of Pharmacology, Cinvestav-IPN, Av. Instituto Politécnico Nacional 2508, Apartado Postal 14-740, 07000, Mexico City, Mexico. pmuriel@cinvestav.mx
Telephone: +52-55-57473303 Fax: +52-55-57473394
Received: November 18, 2016
Peer-review started: November 18, 2016
First decision: March 3, 2017
Revised: March 22, 2017
Accepted: June 1, 2017
Article in press: June 1, 2017
Published online: June 28, 2017
Core Tip

Core tip: To study the effect of naringenin (NAR) on carbon tetrachloride (CCl4)-induced chronic liver fibrosis, male Wistar rats were administered 400 mg of CCl4/kg body weight and 100 mg of NAR/kg body weight for 8 wk. NAR prevented necrosis, cholestasis, oxidative stress, collagen accumulation and the increase in MMP activity caused by CCl4 administration. NAR completely prevented the increase in TGF-β, α-SMA, CTGF, Col-1, MMP-13, NF-κB, IL-1 and IL-10 protein levels caused by CCl4 administration and pSmad3 and pJNK activation. In conclusion, NAR prevents CCl4 induced liver fibrosis due to its antioxidant capacity and by inhibiting the TGF-β-Smad3, JNK-Smad3 and NF-κB pathways.