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从与 Salvadora oleoides Decne. 相关的真菌内生菌中寻找新型抗糖尿病药物的研究

Investigations towards new antidiabetic drugs from fungal endophytes associated with Salvadora oleoides Decne.

机构信息

Department of Genetics, Maharshi Dayanand University, Rohtak 124001, Haryana, India.

出版信息

Med Chem. 2013 Jun 1;9(4):624-32. doi: 10.2174/1573406411309040017.

DOI:10.2174/1573406411309040017
PMID:22946533
Abstract

The nature has provided abundant natural resources which can be explored for their medicinal uses. The present study was undertaken to investigate the antidiabetic and hypolipidemic activity of various extract's fractions obtained from mycelia of seventeen endophytic fungi in different solvents (methanol, acetone and aqueous) isolated from Salvadora oleoides Decne (Salvadoraceae) in glucose loaded fasting and alloxan induced diabetic Wistar albino rats. Only four extracts namely; unidentified fungus (aqueous), Aspergillus sp.JPY2 (methanol), Aspergillus sp.JPY1 (methanol) and Phoma sp. (acetone) significantly reduced blood glucose levels as revealed by glucose tolerance test. It has been observed that in alloxan induced diabetic rats, the maximum reduction in blood glucose level was after 5 hours in the acute treatment experiment and on14th day in sub acute treatment at a dose of 250mg/kg of body weight (P<0.05). The reduction in blood glucose in long term treatment experiment was ranged from 11.3% to 28.04%, whereas standard drug tolbutamide reduced the blood glucose level up to 40%. In long term treatment, unidentified fungus (aqueous) extract showed significant improvement in parameters like body weight and lipid profile of alloxan induced diabetic rats. The gas chromatography mass spectrometer (GCMS) analysis of bioactive fraction (aqueous) of unidentified fungus and methanolic extract fraction of Aspergillus sp.JPY1 revealed that the main constituents were 2, 6-di-tert-butyl-p-cresol and Phenol, 2, 6-bis (1, 1-dimethylethyl)-4-methyl respectively. The results have also suggested that the above four bioactive fractions have good margin of safety and did not show any lethal effects on the animals up to the doses of 1000mg/kg b.w. along with safe doses up to 500 μg/ ml to human erythrocytes.

摘要

自然界提供了丰富的自然资源,可以从中探索其药用价值。本研究旨在研究从 Salvadora oleoides Decne(豆科)中分离得到的 17 种内生真菌的不同溶剂(甲醇、丙酮和水)提取物的 fractions 的抗糖尿病和降血脂活性。只有四种提取物,即:未鉴定真菌(水)、Aspergillus sp.JPY2(甲醇)、Aspergillus sp.JPY1(甲醇)和 Phoma sp.(丙酮),在葡萄糖负荷禁食和链脲佐菌素诱导的 Wistar 白化病大鼠中显著降低血糖水平,如葡萄糖耐量试验所示。在链脲佐菌素诱导的糖尿病大鼠中,在急性治疗实验中,最大的血糖降低发生在 5 小时后,在亚急性治疗中,在 250mg/kg 体重的剂量下,在第 14 天达到最大值(P<0.05)。长期治疗实验中血糖降低幅度为 11.3%至 28.04%,而标准药物甲苯磺丁脲可将血糖水平降低至 40%。在长期治疗中,未鉴定真菌(水)提取物可显著改善链脲佐菌素诱导的糖尿病大鼠的体重和血脂谱参数。未鉴定真菌的生物活性 fraction(水)和 Aspergillus sp.JPY1 的甲醇提取物 fraction 的气相色谱质谱分析(GCMS)表明,主要成分分别为 2,6-二叔丁基对甲酚和 2,6-双(1,1-二甲基乙基)-4-甲基苯酚。结果还表明,上述四种生物活性 fraction 具有良好的安全性边际,在 1000mg/kg b.w. 剂量下对动物没有任何致死作用,同时对人类红细胞的安全剂量高达 500μg/ml。

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