In vivo treatment with the herbal phenylethanoid acteoside ameliorates intestinal inflammation in dextran sulphate sodium-induced colitis

Abstract

SummaryRecently we demonstrated that in inflammatory bowel disease (IBD) macrophage-oxidative burst activity is increased and NADPH oxidase mRNA is induced. The herbal phenylethanoid acteoside isolated from Plantago lanceolata L. was shown to exhibit anti-oxidative potential. Using the dextran sulphate sodium (DSS)-induced colitis model, in this study we have assessed whether systemic application of acteoside affects colitis. Colitis was induced by DSS in Balb/c mice. Treatment with acteoside (120, 600 mg/ mouse/day) was performed intraperitoneally. The colon lengths were determined. Colonic tissue was scored histologically (max. score 8) by a blinded investigator. T cells isolated from mesenteric lymph nodes (MLN) were stimulated with anti-CD3 antibody in the presence of interleukin (IL)-2 (final concentration 10 U/ml). After incubation for 24 h, IL-1b, IL-6, IL-12 tumour necrosis factor (TNF)-a and interferon (IFN)-g levels in supernatants were analysed by the beadlyte® cytokine detection system. Histological scoring of colonic tissue revealed that application of acteoside was followed by a significantly improved histological score. In acute colitis the histological score was 3·2 with acteoside versus 5·2 with phosphate-buffered saline (PBS) (P < 0·02). In chronic colitis both 120 mg (3·3 versus 5·2) or 600 mg acteoside (3·0 versus 5·2) significantly ameliorated colitis (both P < 0·02). Stimulated MLN from mice with chronic DSS-induced colitis treated with acteoside showed a significant down-regulation of IFN-g secretion (195 pg/ml with 600 mg acteoside versus 612 pg/ml with PBS, P < 0·02). Inhibition of oxidative burst activity with acteoside reduced mucosal tissue damage in DSS colitis and could be a therapeutic alternative for IBD treatment. Further studies of this agent are warranted.

Gp91phox contributes to the development of experimental inflammatory bowel disease

“…20 Furthermore, antioxidant administration can reduce mucosal inflammation in IBD. 21 These studies indicate that part of the treatment efficacy of drugs used in the treatment of IBD could be mediated by decreasing the production or effects of ROS. 22 Such information could contribute to future developments in anti-inflammatory therapy.…”

Enoxaparin Improves the Course of Dextran Sodium Sulfate-Induced Colitis in Syndecan-1-Deficient Mice

“…22 Severity of the colitis was assessed by an established scoring system as published before. 23 For immunohistochemical analysis, the following primary antibodies were used: Sdc1 (rat anti-mouse Sdc1 mAb clone 281-2, diluted 1/100 in PBS with 1% BSA; BD Pharmingen, Heidelberg, Germany), Sdc2 (rabbit-antimouse, diluted 1/50; Santa Cruz Biotechnology, Santa Cruz, CA), Sdc3 (rat-anti-mouse mAb clone 312607, diluted 1/50; R&D Systems, Wiesbaden, Germany), Sdc4 (ratanti-mouse clone KY/8.2, diluted 1/50; BD Pharmingen), F4/80 (rat-anti-mouse, clone BM8; eBioscience, San Diego, CA), CD4, CD8, and B220 (rat anti-mouse, clone C3T4 (CD4), clone 53-6.7 (CD8), and clone RA3-6B2 (B220), diluted 1/100; BD Pharmingen). M cells were stained with the UEA1 lectin method (Sigma-Aldrich, Deisenheim, Germany) as described elsewhere.…”

“…23 Briefly, inflammatory activity was characterized by the severity of inflammatory damage and destruction of cytoarchitecture of the gut (loss of epithelial cells (grade 1) On day 9, placebo-treated Sdc1 KO mice showed a strong epithelial disintegration with ulcerations, edema, muscular thickening, and wide areas of epithelial denudation; nearly no intact mucosa was seen (Figure 2A). Colonic tissue from placebo and enoxaparin-treated wildtype mice had less severe signs of epithelial damage with ulcerations and edema; epithelial healing on day 9 was detectable.…”

“…M cells were stained with the UEA1 lectin method (Sigma-Aldrich, Deisenheim, Germany) as described elsewhere. 23 Briefly, the sections were blocked with 10% goat serum or 1% BSA (Dako, Glostrup, Denmark) in PBS for 30 minutes. Incubation with the primary antibody was performed in a humid chamber overnight at 4°C.…”

Phenylethanoid Glycosides: Research Advances in Their Phytochemistry, Pharmacological Activity and Pharmacokinetics

“…Penido et al, revealed that 121 exhibited a potent inhibitory effect on LPS-induced total leucocyte, neutrophil and eosinophil accumulation in the pelural cavity along with a potent antiulcerogenic activity against diclofenac-induced gastric ulcers at 100 mg/kg [84]. Meanwhile, the histological scores indicated that treatment with 121 ameliorated intestinal inflammation in both acute and chronic dextran sulphate sodium-induced colitis in vivo through inhibition of oxidative burst activity [85]. Cell adhesion molecules (CAMs) play a role in the pathogenesis of atherosclerosis and inflammation.…”