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竹提取物对肝生物转化酶的影响——肥胖型糖尿病小鼠模型的研究结果。

The effect of bamboo extract on hepatic biotransforming enzymes--findings from an obese-diabetic mouse model.

机构信息

Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA.

出版信息

J Ethnopharmacol. 2011 Jan 7;133(1):37-45. doi: 10.1016/j.jep.2010.08.062. Epub 2010 Sep 9.

Abstract

AIM OF THE STUDY

Bamboo leaves are used as a component in traditional Chinese medicine for the anti-inflammatory function. Our previous studies have demonstrated that an ethanol/water extract from Phyllostachys edulis ameliorated obesity-associated chronic systemic inflammation in mice, and therefore relieving the symptoms of type 2 diabetes. The aim of this project was to further investigate the effects of this bamboo extract on hepatic biotransformation enzymes in both lean and obese mice, as an initial step in the toxicological evaluation of using this traditional medicine in obese/diabetic population.

MATERIALS AND METHODS

Male C57BL/6J mice were randomized to 4 groups and fed standard (10% kcal from fat) diet with or without bamboo extract supplementation at a dose of 10 gram per kilogram diet (n=10 and n=9, respectively), or high fat (45% kcal from fat) diet with or without bamboo extract (n=8 and N=7, respectively). The dietary treatment lasted for 6 months. Subsequently, the activities and expression of the major Phase I and II hepatic biotransformation enzymes were assessed in subcellular fractions from murine livers.

RESULTS

Three groups of mice, lean bamboo extract-supplemented, obese/diabetic, and bamboo extract-supplemented obese/diabetic, showed greater activities of cytochromes P450 1a2 and 3a11 compared to control but no changes in the expression level of these proteins. For Phase II enzymes, bamboo extract supplementation in lean mice caused decreased glutathione-S-transferase activity (-12%) and greater uridine diphosphate glucuronosyltransferase activity (+46%), but had no effect on sulfotransferase activity. Conversely, the obese/diabetic condition itself increased glutathione-S-transferase and uridine diphosphate glucuronosyltransferase activities, but decreased total sulfotransferase activity and sulfotransferase 2a1 expression.

CONCLUSIONS

Bamboo extract and obesity/diabetes show significant independent effects on hepatic biotransformation as well as interaction effects in mice. These changes may alter the clearance of endo- and xenobiotics, including bamboo extract itself, hence this effect should be carefully considered in the medicinal application of bamboo extract as it has potential to alter its own metabolism and that of other medications concurrently administered to obese diabetic patients.

摘要

研究目的

竹叶在中国传统医学中被用作抗炎成分。我们之前的研究表明,从淡竹中提取的乙醇/水提取物可改善肥胖相关的慢性全身炎症,从而缓解 2 型糖尿病的症状。本项目旨在进一步研究这种竹提取物对瘦鼠和肥胖鼠肝生物转化酶的影响,作为评估在肥胖/糖尿病人群中使用这种传统药物的毒理学的初步步骤。

材料和方法

雄性 C57BL/6J 小鼠随机分为 4 组,分别给予标准(10%脂肪热量)饮食和补充 10 克/千克饮食剂量的竹提取物(n=10 和 n=9),或高脂肪(45%脂肪热量)饮食和补充竹提取物(n=8 和 n=7)。饮食处理持续 6 个月。随后,评估了来自小鼠肝脏亚细胞部分的主要 I 相和 II 相肝生物转化酶的活性和表达。

结果

三组小鼠,即补充竹提取物的瘦鼠、肥胖/糖尿病鼠和补充竹提取物的肥胖/糖尿病鼠,与对照组相比,细胞色素 P450 1a2 和 3a11 的活性更高,但这些蛋白质的表达水平没有变化。对于 II 相酶,瘦鼠补充竹提取物导致谷胱甘肽-S-转移酶活性降低(-12%)和尿苷二磷酸葡萄糖醛酸转移酶活性增加(+46%),但对磺基转移酶活性没有影响。相反,肥胖/糖尿病状态本身增加了谷胱甘肽-S-转移酶和尿苷二磷酸葡萄糖醛酸转移酶的活性,但降低了总磺基转移酶活性和磺基转移酶 2a1 的表达。

结论

竹提取物和肥胖/糖尿病对小鼠的肝生物转化有显著的独立作用和相互作用。这些变化可能改变内源性和外源性物质的清除率,包括竹提取物本身,因此,在肥胖糖尿病患者同时服用竹提取物及其它药物时,应仔细考虑这种作用,因为它有可能改变其自身代谢和同时服用的其它药物的代谢。

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