Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2017; 23(47): 8308-8320
Published online Dec 21, 2017. doi: 10.3748/wjg.v23.i47.8308
Effects of initiating time and dosage of Panax notoginseng on mucosal microvascular injury in experimental colitis
Shi-Ying Wang, Ping Tao, Hong-Yi Hu, Jian-Ye Yuan, Lei Zhao, Bo-Yun Sun, Wang-Jun Zhang, Jiang Lin
Shi-Ying Wang, Ping Tao, Hong-Yi Hu, Lei Zhao, Bo-Yun Sun, Wang-Jun Zhang, Jiang Lin, Department of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
Shi-Ying Wang, Hong-Yi Hu, Jian-Ye Yuan, Institute of Digestive Diseases, China-Canada Center of Research for Digestive Diseases (ccCRDD), Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
Author contributions: Wang SY performed the experiments, prepared the figures, and contributed to the manuscript writing; Tao P, Zhao L, Sun BY and Zhang WJ performed the experiments and analyzed the data; Tao P and Zhang WJ provided research materials; Yuan JY and Hu HY contributed to experimental design; Lin J contributed to experimental design, interpretation of data, and manuscript writing, and supervised the project; all authors approved the final version.
Supported by the National Natural Science Foundation of China, No. 81373616.
Institutional review board statement: The following study has been reviewed and approved by the Institutional Review Board of Longhua Hospital, Shanghai University of Traditional Chinese Medicine.
Institutional animal care and use committee statement: All procedures involving animals in the following manuscript were reviewed and approved by the Institutional Animal Care and Use Committee of Shanghai University of Traditional Chinese Medicine (No. SZY201612006).
Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study.
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: Jiang Lin, PhD, MD, Chief Doctor, Professor, Department of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, No. 725, South Wanping Road, Shanghai 200032, China. linjiang@longhua.net
Telephone: +86-21-64385700 Fax: +86-21-64398310
Received: September 6, 2017
Peer-review started: September 7, 2017
First decision: October 10, 2017
Revised: November 3, 2017
Accepted: November 14, 2017
Article in press: November 14, 2017
Published online: December 21, 2017
ARTICLE HIGHLIGHTS
Research background

Panax notoginseng (PN) is a Chinese herbal medicine commonly used to treat ulcerative colitis (UC) and vascular diseases. Microvascular injury plays an important role in the pathogenesis of UC, but PN’s effects on microvascular injury in UC are unclear. To clarify the effects of PN on microvascular injury is important for treating UC.

Research motivation

The effects of PN on microvascular injury in colitis, its initial administration time, its dosage and its related mechanisms were investigated. These are important questions for using PN for treatment of UC.

Research objectives

To clarify the effects of PN on microvascular injury and related affecting factors, as well as its mechanisms.

Research methods

Dextran sodium sulfate (DSS)- or iodoacetamide (IA)-induced rat colitis models were used. PN administration was initiated at 3 d and 7 d after the model was established at doses of 0.5, 1.0 and 2.0 g/kg for seven consecutive days. The severity of colitis was evaluated by disease activity index (DAI). The pathological lesions were observed under microscope. Microvessel density (MVD) was evaluated by immunohistochemistry. Vascular permeability was evaluated using the Evans blue method. The serum concentrations of vascular endothelial growth factor (VEGF)A121, VEGFA165, interleukin (IL)-4, IL-6, IL-10 and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay. Myeloperoxidase (MPO) and superoxide dismutase (SOD) were measured to evaluate the level of oxidative stress. Expression of hypoxia-inducible factor (HIF)-1α protein was detected by western blotting. One-way ANOVA or general linear model with repeated measures was used to analyze the data sets with three or more groups, and least significant difference post hoc test for multiple comparisons. Student’s t-test was used to analyze data sets with two groups. P < 0.05 was considered significant.

Research results

Obvious colonic inflammation and injuries of colonic mucosa and microvessels were observed in DSS- and IA-induced colitis in rats. DAI scores, the serum concentrations of VEGFA121, VEGFA165, VEGFA165/VEGFA121, IL-6 and TNF-α, and the concentrations of MPO and HIF-1α in the colon were significantly higher while the serum concentrations of IL-4 and IL-10 and MVD in colon were significantly lower in the colitis model groups than in the normal control group. PN promoted repair of the injuries of colonic mucosa and microvessels, attenuated inflammation and decreased DAI scores in rats with colitis. PN decreased the serum concentrations of VEGFA121, VEGFA165, VEGFA165/VEGFA121, IL-6 and TNF-α and the concentrations of MPO and HIF-1α in the colon. It also increased the serum concentrations of IL-4 and IL-10 as well as the concentration of SOD in the colon. The efficacy of PN was dosage dependent. In addition, DAI scores in the group initiating PN administration on day 3 were significantly lower than in the group initiating PN administration on day 7.

Research conclusions

PN repaired microvessel injury in experimental colitis via attenuating inflammation and oxidative stress in the colonic mucosa. The efficacy of PN was related to the initial administration time and the dose.

Research perspectives

Finding the real effective component in PN and clarifying the mechanisms of PN attenuating oxidative stress and regulating angiogenesis will be conducted in the future studies.