Original Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 28, 2013; 19(48): 9318-9327
Published online Dec 28, 2013. doi: 10.3748/wjg.v19.i48.9318
Effectiveness of a hydroxynaphthoquinone fraction from Arnebia euchroma in rats with experimental colitis
Hua-Ying Fan, Zi-Liang Zhang, Ke Liu, Ming-Yan Yang, Wei-Hong Lv, Xin Che, Hui Xu, Wei-Wei Song
Hua-Ying Fan, Wei-Wei Song, Ke Liu, Ming-Yan Yang, Xin Che, Hui Xu, School of Pharmacy, Yantai University, Yantai 264005, Shandong Province, China
Zi-Liang Zhang, College of Life Science, Jilin University, Changchun 130012, Jilin Province, China
Ke Liu, Ming-Yan Yang, Xin Che, Hui Xu, Shandong Target Drug Research Co. Ltd., Yantai 264005, Shandong Province, China
Wei-Hong Lv, Shandong Target Drug Research Co. Ltd., Yantai 264005, Shandong Province, China
Author contributions: Fan HY and Liu K designed the research; Zhang ZL, Yang MY, Che X, Lv WH and Song WW performed the research; Xu H analyzed the data; and Yang MY and Song WW wrote the paper.
Supported by National Program for Important New Drugs R and D, No. 2011ZX9102-006-04; Programs for Science and Technology Development and Plan of Yantai, No. 2013ZH086
Correspondence to: Wei-Wei Song, Master of Medicine, School of Pharmacy, Yantai University, No. 32 Qingquan Road, Yantai 264005, Shandong Province, China. songweiwei2011@163.com
Telephone: +86-535-6706030 Fax: +86-535-6706066
Received: August 28, 2013
Revised: October 16, 2013
Accepted: November 1, 2013
Published online: December 28, 2013
Processing time: 139 Days and 4.1 Hours
Abstract

AIM: To evaluate the potential effectiveness of hydroxynaphthoquinone mixture (HM) in rats with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis.

METHODS: Colitis was induced by intracolonic administration of TNBS (80 mg/kg, dissolved in 50% ethanol). Rats were treated daily for 7 d with HM (2.5, 5, 10 mg/kg) and mesalazine 100 mg/kg 24 h after TNBS instillation. Disease progression was monitored daily by observation of clinical signs and body weight change. At the end of the experiment, macroscopic and histopathologic lesions of rats were scored, and myeloperoxidase (MPO) activity was determined. We also determined inflammatory cytokine tumor necrosis factor (TNF)-α level by ELISA, Western blotting and immunochemistry to explore the potential mechanisms of HM.

RESULTS: After intracolonic instillation of TNBS, animals developed colitis associated with soft stool, diarrhea and marked colonic destruction. Administration of HM significantly attenuated clinical and histopathologic severity of TNBS-induced colitis in a dose-dependent manner. It abrogated body weight loss, diarrhea and inflammation, decreased macroscopic damage score, and improved histological signs, with a significant reduction of inflammatory infiltration, ulcer size and the severity of goblet cell depletion (all P < 0.05 vs TNBS alone group). HM could reduce MPO activity. In addition, it also decreased serum TNF-α level and down-regulated TNF-α expression in colonic tissue. This reduction was statistically significant when the dose of HM was 10 mg/kg (P < 0.05 vs TNBS alone group), and the effect was comparable to that of mesalazine and showed no apparent adverse effect. The underlying mechanism may be associated with TNF-α inhibition.

CONCLUSION: These findings suggest that HM possesses favourable therapeutic action in TNBS-induced colitis, which provides direct pharmacological evidence for its clinical application.

Keywords: Arnebia euchroma (Royle) Johnst; Hydroxynaphthoquinones; Inflammatory bowel disease; 2,4,6-trinitrobenzene sulfonic acid-induced colitis; Tumor necrosis factor

Core tip: Current therapies for inflammatory bowel disease are limited by lack of effectiveness, drug refractoriness or severe adverse effects. Therefore, there is an urgent need for more effective and safe therapeutic approaches. Due to their favourable effect and less side effects, looking for novel agents from herbal and natural products has been a research focus for a long time. Previous studies demonstrate that hydroxynaphthoquinones exert therapeutic action on chronic inflammatory disease. In this study, hydroxynaphthoquinones showed beneficial effect on 2,4,6-trinitrobenzene sulfonic acid-induced colitis via tumor necrosis factor-α inhibition, and the effect was comparable to that of mesalazine. This provides pharmacological evidence for its clinical application.