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绿茶多酚和柳氮磺胺吡啶在结肠炎模型中具有平行的抗炎特性。

Green Tea Polyphenols and Sulfasalazine have Parallel Anti-Inflammatory Properties in Colitis Models.

机构信息

Department of Internal Medicine, University of Kentucky Medical Center , Lexington, KY , USA.

出版信息

Front Immunol. 2013 Jun 5;4:132. doi: 10.3389/fimmu.2013.00132. eCollection 2013.

Abstract

BACKGROUND

There is no cure for autoimmune chronic inflammatory bowel disease (IBD). IBD patients commonly use complementary and alternative medications of which the safety, efficacy, and interaction with standard-of-care therapies are not fully known. Thus the consequences can become life-threatening. Sulfasalazine commonly used in IBD, potentially has severe adverse effects, including infertility, pulmonary fibrosis, lack of response, and ultimately patients may require intestinal resection. We hypothesized that green tea polyphenols (GrTP, EGCG) and sulfasalazine have similar anti-inflammatory properties.

METHODS

BALB/c mice received Dextran sodium sulfate (DSS) to induce colitis (ulcerative colitis model). Exposure of IL-10 deficient mice (BALB/c-background) to normal microbiota provoked enterocolitis (mimics Crohn's disease). Animals were treated with agents incorporated into daily diets. Control animals received sham treatment.

RESULTS

DSS-treated animals developed severe bloody diarrhea and colitis (score 0-4, 3.2 ± 0.27). IL-10 deficient mice developed severe enterocolitis as manifested by diarrhea, rectal prolapse, and colonic lesions. Animals tolerated regimens (GrTP, EGCG, sulfasalazine) with no major side effects, and further developed less severe colitis. IL-10 deficient animals became moribund on high dose, while tolerated low and Mid doses with significant improved symptoms of enterocolitis. GrTP, EGCG, and sulfasalazine significantly ameliorated colonic damage and histological scores in treated animals in a similar manner (GrTP vs. DSS p < 0.05; EGCG, sulfasalazine vs. DSS p < 0.01). The inflammatory markers TNFα (3-fold), IL-6 (14-fold), and serum amyloid A (40-fold) increased in colitic animals and significantly decreased with treatment regiments. In contrast, circulatory leptin levels decreased in colitic animals (twofold). EGCG additionally reduced leptin levels (p < 0.01) while GrTP and sulfasalazine had no effect on leptin levels (p < 0.05). Hepatic and colonic antioxidants were significantly depleted in colitic animals and treatment regiments significantly restored antioxidants levels.

CONCLUSION

GrTP and EGCG improved antioxidants levels and attenuated severity of colitis analogous to sulfasalazine. Future studies will reveal whether polyphenols can become an alternative/additive therapy for IBD therapy in humans.

摘要

背景

目前尚无治愈自身免疫性慢性炎症性肠病(IBD)的方法。IBD 患者通常会使用补充和替代药物,但这些药物的安全性、疗效以及与标准治疗方法的相互作用尚不完全清楚。因此,这些药物的使用可能会危及生命。柳氮磺胺吡啶常用于治疗 IBD,但可能会产生严重的副作用,包括不孕、肺纤维化、无应答,最终患者可能需要进行肠道切除术。我们假设绿茶多酚(GrTP、EGCG)和柳氮磺胺吡啶具有相似的抗炎特性。

方法

BALB/c 小鼠接受葡聚糖硫酸钠(DSS)诱导结肠炎(溃疡性结肠炎模型)。IL-10 缺陷小鼠(BALB/c 背景)暴露于正常菌群中会引发肠炎(模仿克罗恩病)。动物接受掺入日常饮食中的药物治疗。对照动物接受假处理。

结果

DSS 处理的动物出现严重的血性腹泻和结肠炎(评分 0-4,3.2±0.27)。IL-10 缺陷小鼠出现严重肠炎,表现为腹泻、直肠脱垂和结肠病变。动物耐受了没有明显副作用的治疗方案(GrTP、EGCG、柳氮磺胺吡啶),并进一步发展为较轻的结肠炎。高剂量的 IL-10 缺陷动物濒死,而低剂量和中剂量的动物则耐受良好,肠炎症状明显改善。GrTP、EGCG 和柳氮磺胺吡啶以相似的方式显著改善了治疗动物的结肠损伤和组织学评分(GrTP 与 DSS 相比,p<0.05;EGCG、柳氮磺胺吡啶与 DSS 相比,p<0.01)。促炎标志物 TNFα(增加 3 倍)、IL-6(增加 14 倍)和血清淀粉样蛋白 A(增加 40 倍)在结肠炎动物中升高,并随治疗方案显著降低。相反,循环瘦素水平在结肠炎动物中降低(降低 2 倍)。EGCG 还降低了瘦素水平(p<0.01),而 GrTP 和柳氮磺胺吡啶对瘦素水平没有影响(p<0.05)。肝和结肠中的抗氧化剂在结肠炎动物中明显耗竭,而治疗方案则显著恢复了抗氧化剂水平。

结论

GrTP 和 EGCG 提高了抗氧化剂水平,并减轻了结肠炎的严重程度,与柳氮磺胺吡啶类似。未来的研究将揭示多酚是否可以成为人类 IBD 治疗的替代/附加治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9258/3672863/3a680c2726ec/fimmu-04-00132-g001.jpg

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