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以调控炎症和氧化介质为靶点,筛选速清丸优化方对 DSS 诱导的溃疡性结肠炎的治疗作用。

Screening of the optimized prescription from Suqingwan in terms of its therapeutic effect on DSS-induced ulcerative colitis by its regulation of inflammatory and oxidative mediators.

机构信息

Development and Utilization Key Laboratory of Northeast Plant Materials, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.

Development and Utilization Key Laboratory of Northeast Plant Materials, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.

出版信息

J Ethnopharmacol. 2017 Apr 18;202:54-62. doi: 10.1016/j.jep.2017.03.006. Epub 2017 Mar 8.

DOI:10.1016/j.jep.2017.03.006
PMID:28284792
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Suqingwan (SQW), a traditional Chinese medicine used for treating ulcerative colitis (UC), is composed of 13 kinds of Traditional Chinese medicines (TCMs). According to TCM theory, we investigated whether a simplified prescription composed of the herbs with some functions, would have similar effects to SQW and examined its potential treatment mechanism of action.

MATERIALS AND METHODS

We categorized the herbs in SQW into four groups according to their traditional functions and used an orthogonal experimental design to obtain nine separated prescriptions (SPs) of SQW. A dextran sulfate sodium (DSS)-induced UC mouse model was used to evaluate the anti-ulcer colitis effects of the nine SPs and the calculated prescription (CP) was obtained based on the orthogonal t values of the disease activity index (DAI) of the nine SPs. The effect of the CP and SP8 were verified in the DSS-induced UC model, and the DAI and histopathology of the UC mice were examined. Myeloperoxidase (MPO), malondialdehyde (MDA), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-4 and IL-10 of the mice in SP8 were investigated to explore the mechanism of action of the optimized prescription with regard to anti-inflammatory and anti-oxidation effects.

RESULTS

Among the 9 SPs, separate prescription 6, 7 and 8 (SP6, SP7 and SP8) and the SQW formulation all significantly reduced the DAI of the UC mice and, in particular, SP8 had an effect similar to SQW, which consists of Sanguisorba officinalis L., Rehmannia glutinosa Libosch. and four other herbal medicines. In a further investigation, SP8 was found to improve the ulcerative colitis in mice in terms of both clinical symptoms and histopathology. The mortality of mice in the SP8 group was 33.3%, better than CP based on the orthogonal t values (83.3%). SP8 could also reduce the levels of TNF-α, IL-1β, IL-6, MPO and MDA and increase the levels of IL-4 and IL-10 in colon tissue of UC mice in comparison with those of the model group (p<0.05).

CONCLUSIONS

An optimized prescription (SP8) from SQW was obtained based on an orthogonal experimental design, which involved 6 herbal medicines, with significantly fewer herbs than in the original prescription. SP8 displayed a similar anti-ulcerative colitis activity to SQW, and its in vivo mechanism of action is related to up-regulation of anti-inflammatory cytokines and down-regulation of pro-inflammatory and oxidative factors.

摘要

民族药理学相关性

素清丸(SQW)是一种用于治疗溃疡性结肠炎(UC)的中药,由 13 种中药组成。根据中医理论,我们研究了由具有某些功能的草药组成的简化处方是否具有与 SQW 相似的作用,并探讨了其潜在的治疗作用机制。

材料和方法

我们根据传统功能将 SQW 中的草药分为四组,并用正交实验设计获得了九种分离的 SQW 处方(SP)。使用葡聚糖硫酸钠(DSS)诱导的 UC 小鼠模型来评估九种 SP 的抗溃疡性结肠炎作用,并根据九种 SP 的疾病活动指数(DAI)的正交 t 值计算出处方(CP)。验证 CP 和 SP8 在 DSS 诱导的 UC 模型中的作用,并检查 UC 小鼠的 DAI 和组织病理学。研究了 SP8 中小鼠髓过氧化物酶(MPO)、丙二醛(MDA)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-6、IL-4 和 IL-10,以探讨抗炎和抗氧化作用的优化处方的作用机制。

结果

在 9 种 SP 中,单独的处方 6、7 和 8(SP6、SP7 和 SP8)和 SQW 配方均显著降低 UC 小鼠的 DAI,特别是 SP8 具有与 SQW 相似的作用,由 Sanguisorba officinalis L.、地黄(Rehmannia glutinosa Libosch.)和其他四种草药组成。进一步的研究发现,SP8 在改善溃疡性结肠炎的临床症状和组织病理学方面均优于基于正交 t 值的 CP。SP8 组小鼠的死亡率为 33.3%,优于基于正交 t 值的 CP(83.3%)。SP8 还可以降低 UC 小鼠结肠组织中 TNF-α、IL-1β、IL-6、MPO 和 MDA 的水平,并增加抗炎细胞因子 IL-4 和 IL-10 的水平,与模型组相比(p<0.05)。

结论

基于正交实验设计,从 SQW 中获得了优化处方(SP8),涉及 6 种草药,比原处方少。SP8 显示出与 SQW 相似的抗溃疡性结肠炎活性,其体内作用机制与上调抗炎细胞因子和下调促炎和氧化因子有关。

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