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Front. Physiol. | doi: 10.3389/fphys.2019.00956

Protective Effect of Ursolic Acid on the Intestinal Mucosal Barrier in a Rat Model of Liver Fibrosis

 Wang Zhang1, Dakai Gan1,  Jie Jian1,  Chenkai Huang1, Fangyun Luo1,  Sizhe Wan1, Meichun Jiang1, Yipeng Wan1, Anjiang Wang1, Bimin Li1* and  Zhu Xuan1*
  • 1First Affiliated Hospital of Nanchang University, China

Oxidative stress mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) plays an important role in intestinal mucosal barrier damage in various disease states. Recent evidence suggests that intestinal mucosal barrier damage and intestinal dysbiosis occur in mice with hepatic fibrosis induced by CCl4 or bile duct ligation. Another study showed that ursolic acid (UA) attenuates experimental colitis via its antiinflammatory and antioxidant activities. The goal of this study was to investigate the effects of UA on the intestinal mucosal barrier in CCl4-induced hepatic fibrosis rats and identify its associated mechanisms. Male Sprague-Dawley (SD) rats were randomly divided into the following 3 groups (n=10/group): the control, CCl4 model and UA treatment groups. Rats were sacrificed at 72 h after the hepatic fibrosis model was established and assessed for liver fibrosis, intestinal injury, enterocyte apoptosis, bacterial translocation, system inflammation, intestinal oxidative stress, and tight junction protein and NOX protein expression. The results demonstrated that UA attenuated the following: ⅰ) liver and intestinal pathological injury; ⅱ) cleaved caspase-3 expression in the ileal epithelial cells; ⅲ) serum lipopolysaccharide and procalcitonin levels; ⅳ) intestinal malondialdehyde levels; and ⅴ) the expression of the NOX protein components NOX2 and P67phox in ileal tissues. Furthermore, our results suggested that UA improved intestinal dysbiosis and the expression of the tight junction proteins Claudin 1 and Occludin in the ilea of rats. These results indicate that UA has protective effects on the intestinal mucosal barrier in rats with CCl4-induced liver fibrosis by inhibiting intestinal NOX-mediated oxidative stress. Our findings may provide a basis for further clinical studies of UA as a novel and adjuvant treatment to cure liver fibrosis.

Keywords: hepatic fibrosis, intestinal mucosal barrier function, ursolic acid, NOX, intestinal microbiota

Received: 04 Feb 2019; Accepted: 09 Jul 2019.

Edited by:

Petra Hirsova, Charles University, Czechia

Reviewed by:

Ekihiro Seki, Cedars-Sinai Medical Center, United States
Ana C. Llorente Izquierdo, University of California, San Diego, United States  

Copyright: © 2019 Zhang, Gan, Jian, Huang, Luo, Wan, Jiang, Wan, Wang, Li and Xuan. 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(s) 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. Bimin Li, First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China, lbmjx@163.com
Prof. Zhu Xuan, First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China, jyyfyzx@163.com