College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
J Ethnopharmacol. 2011 Jan 27;133(2):780-7. doi: 10.1016/j.jep.2010.11.010. Epub 2010 Nov 9.
To investigate the effects and the protective mechanism of iridoid glycosides (IG) enriched from Folium syringae leaves on ulcerative colitis (UC) model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats.
UC in rats was induced by colonic administration with TNBS. IG (80, 160 and 240 mg/kg) was administered for 2 weeks to experimental colitis rats. The inflammatory degree was assessed by macroscopic score, histology and myeloperoxidase (MPO) activity. Nitric oxide (NO) and malondialdehyde (MDA) levels were measured with biochemical methods. The protein expressions of nuclear factor-kappaBp65 (NF-κBp65) and mRNA expressions of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and NF-κBp65, were determined by immunohistochemistry and real-time quantitative PCR, respectively.
IG significantly ameliorated macroscopic damage and histological changes, reduced the activity of MPO, depressed MDA and NO levels and effectively inhibited the protein and mRNA expressions of NF-κBp65, TNF-α and IL-6 in the colon tissues of experimental colitis in a dose-dependent manner. Moreover, the effects of IG (160 mg/kg and 240 mg/kg) were superior to salicylazosulfapyridine (150 mg/kg).
We demonstrated for the first time that IG possessed marked protective effects on experimental colitis through its antioxidation and inhibiting inflammatory mediators by down-regulation of the expressions of NF-κBp65.
研究从丁香叶中提取的环烯醚萜苷(IG)对 2,4,6-三硝基苯磺酸(TNBS)诱导的大鼠溃疡性结肠炎(UC)模型的作用及保护机制。
采用结肠内给予 TNBS 的方法诱导大鼠 UC。IG(80、160 和 240mg/kg)给实验性结肠炎大鼠灌胃 2 周。通过大体评分、组织学和髓过氧化物酶(MPO)活性评估炎症程度。采用生化方法测定一氧化氮(NO)和丙二醛(MDA)水平。用免疫组化和实时定量 PCR 分别测定核因子-κBp65(NF-κBp65)的蛋白表达和促炎细胞因子,如肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和 NF-κBp65 的 mRNA 表达。
IG 显著改善了大体损伤和组织学变化,降低了 MPO 活性,降低了 MDA 和 NO 水平,并有效抑制了实验性结肠炎结肠组织中 NF-κBp65、TNF-α和 IL-6 的蛋白和 mRNA 表达,呈剂量依赖性。此外,IG(160mg/kg 和 240mg/kg)的作用优于柳氮磺胺吡啶(150mg/kg)。
我们首次证明,IG 通过下调 NF-κBp65 的表达,具有抗氧化和抑制炎症介质的作用,对实验性结肠炎具有显著的保护作用。