Effects of initiating time and dosage of Panax notoginseng on mucosal microvascular injury in experimental colitis.

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.

• Authors: Shi-Ying Wang, Ping Tao, Hong-Yi Hu, Jian-Ye Yuan, Lei Zhao, Bo-Yun Sun, Wang-Jun Zhang, Jiang Lin
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 23 Issue 47 Pg. 8308-8320 (Dec 21 2017) ISSN: 2219-2840 [Electronic] United States
• PMID: 29307991 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Drugs, Chinese Herbal
• Vascular Endothelial Growth Factor A
• Dextran Sulfate

Topics

• Animals
• Colitis, Ulcerative (blood, chemically induced, drug therapy, pathology)
• Colon (blood supply)
• Cytokines (blood)
• Dextran Sulfate (toxicity)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal (pharmacology, therapeutic use)
• Humans
• Intestinal Mucosa (blood supply, drug effects, pathology)
• Microvessels (drug effects, pathology)
• Oxidative Stress (drug effects)
• Panax notoginseng (chemistry)
• Rats
• Rats, Sprague-Dawley
• Time Factors
• Treatment Outcome
• Vascular Endothelial Growth Factor A