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
Processing time: 105 Days and 0.5 Hours
Abstract
AIM

To investigate the effects of Panax notoginseng (PN) on microvascular injury in colitis, its mechanisms, initial administration time and dosage.

METHODS

Dextran sodium sulfate (DSS)- or iodoacetamide (IA)-induced rat colitis models were used to evaluate and investigate the effects of ethanol extract of PN on microvascular injuries and their related mechanisms. PN administration was initiated at 3 and 7 d after the model was established at doses of 0.5, 1.0 and 2.0 g/kg for 7 d. The severity of colitis was evaluated by disease activity index (DAI). The pathological lesions were observed under a microscope. Microvessel density (MVD) was evaluated by immunohistochemistry. Vascular permeability was evaluated using the Evans blue method. The serum concentrations of cytokines, including 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.

RESULTS

Obvious colonic inflammation and injuries of mucosa and microvessels were observed in DSS- and IA-induced colitis groups. DAI scores, serum concentrations of VEGFA121, VEGFA165, VEGFA165/VEGFA121, IL-6 and TNF-α, and concentrations of MPO and HIF-1α in the colon were significantly higher while 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 injuries of colonic mucosa and microvessels, attenuated inflammation, and decreased DAI scores in rats with colitis. PN also decreased the serum concentrations of VEGFA121, VEGFA165, VEGFA165/VEGFA121, IL-6 and TNF-α, and concentrations of MPO and HIF-1α in the colon, and 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 administered PN on day 3 were significantly lower than in the group administered PN on day 7.

CONCLUSION

PN repairs vascular injury in experimental colitis via attenuating inflammation and oxidative stress in the colonic mucosa. Efficacy is related to initial administration time and dose.

Keywords: Microvascular injury; Panax notoginseng; Ulcerative colitis; Oxidative stress

Core tip:Panax notoginseng (PN) is a traditional Chinese medicine used to treat ulcerative colitis, but its mechanisms are unclear. In our study, we found that PN promoted repair of injuries of colonic mucosa and microvessels in rat colitis. PN decreased concentrations of vascular endothelial growth factor, interleukin (IL)-6 and tumor necrosis factor-α while it increased the concentrations of IL-4 and IL-10 in serum. It also decreased concentrations of myeloperoxidase and hypoxia-inducible factor-1α while it increased the concentration of superoxide dismutase in colon. So it is concluded that PN repairs mucosal and vascular injuries in rat colitis via attenuating inflammation and oxidative stress in the colonic mucosa.