Published online Dec 21, 2017. doi: 10.3748/wjg.v23.i47.8308
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
To investigate the effects of Panax notoginseng (PN) on microvascular injury in colitis, its mechanisms, initial administration time and dosage.
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.
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.
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.
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.