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紫檀芪中的一种异黄酮对L6肌管中Glut-4和PPARγ的上调作用:一种可能的作用机制。

Upregulation of Glut-4 and PPAR gamma by an isoflavone from Pterocarpus marsupium on L6 myotubes: a possible mechanism of action.

作者信息

Anandharajan R, Pathmanathan K, Shankernarayanan N P, Vishwakarma Ram A, Balakrishnan Arun

机构信息

Centre For Biotechnology, Anna University, Chennai 600025, Tamil Nadu, India.

出版信息

J Ethnopharmacol. 2005 Feb 28;97(2):253-60. doi: 10.1016/j.jep.2004.11.023. Epub 2005 Jan 13.

Abstract

The purpose of the present study is to analyse the influence of Pterocarpus marsupium methanolic extract and isolated Pterocarpus marsupium isoflavone on a battery of cellular targets Glut-4, PPAR gamma and PI3 kinase. Pterocarpus marsupium is an anti-diabetic plant indigenous to South India. Sequential extraction performed with different solvents were analysed for glucose uptake activity at each step. Fraction-9 showing maximum glucose activity on glucose uptake was purified by column chromatography and the structure was elucidated as 7-O-alpha-L-rhamnopyranosyl oxy-4'-methoxy-5-hydroxy isoflavone using NMR and mass spectroscopy. The significant glucose uptake showed by Pterocarpus marsupium crude and pure was comparable with insulin and rosiglitazone. Elevation of Glut-4 and PPARgamma gene expression in parallel with glucose uptake supported the in vitro glucose uptake activity of Pterocarpus marsupium methanolic extract and Pterocarpus marsupium isoflavone. The inhibitory effect of cycloheximide on Pterocarpus marsupium methanolic extract and Pterocarpus marsupium isoflavone-mediated glucose uptake suggested that new protein synthesis is required for elevated Glut-4 protein expression. PI3 kinase plays an important role in glucose transport and activated by Pterocarpus marsupium methanolic extract but not the isolated pure isoflavone. Therefore, we postulate that the isoflavone from Pterocarpus marsupium may activate glucose transport by a PI3 kinase independent pathway, which require further analysis.

摘要

本研究的目的是分析紫檀甲醇提取物和分离出的紫檀异黄酮对一系列细胞靶点(葡萄糖转运蛋白4、过氧化物酶体增殖物激活受体γ和磷脂酰肌醇-3激酶)的影响。紫檀是一种原产于印度南部的抗糖尿病植物。对用不同溶剂进行的连续萃取过程中的每一步进行葡萄糖摄取活性分析。通过柱色谱法纯化了在葡萄糖摄取方面显示出最大葡萄糖活性的馏分9,并使用核磁共振和质谱法将其结构鉴定为7-O-α-L-鼠李糖吡喃糖氧基-4'-甲氧基-5-羟基异黄酮。紫檀粗提物和纯化物所显示的显著葡萄糖摄取与胰岛素和罗格列酮相当。葡萄糖转运蛋白4和过氧化物酶体增殖物激活受体γ基因表达的升高与葡萄糖摄取平行,这支持了紫檀甲醇提取物和紫檀异黄酮的体外葡萄糖摄取活性。环己酰亚胺对紫檀甲醇提取物和紫檀异黄酮介导的葡萄糖摄取的抑制作用表明,葡萄糖转运蛋白4蛋白表达升高需要新的蛋白质合成。磷脂酰肌醇-3激酶在葡萄糖转运中起重要作用,并且被紫檀甲醇提取物激活,但未被分离出的纯异黄酮激活。因此,我们推测紫檀中的异黄酮可能通过一条不依赖磷脂酰肌醇-3激酶的途径激活葡萄糖转运,这需要进一步分析。

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