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首页> 外文期刊>Bioorganic and Medicinal Chemistry Letters >Antidiabetic effect, antioxidant activity, and toxicity of 3 ',4 '-Di-O-acetyl-cis-khellactone in Streptozotocin-induced diabetic rats
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Antidiabetic effect, antioxidant activity, and toxicity of 3 ',4 '-Di-O-acetyl-cis-khellactone in Streptozotocin-induced diabetic rats

机译：3'，4'-Di-O-乙酰基-顺式-甲壳酮在链脲佐菌素诱导的糖尿病大鼠中的抗糖尿病作用，抗氧化活性和毒性

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摘要

Pyranocoumarins are compounds with an important pharmacological profile, such as anti-inflammatory, antioxidant, cytotoxic, antiviral, antibacterial, and hypoglycemic effects. These molecules have a widespread presence as secondary metabolites in medicinal plants used to treat Diabetes Mellitus (DM). The aim of this work was to evaluate antidiabetic activity in Streptozotocin (STZ)-induced diabetic rats and the antioxidant effects of 3',4'-Di-O-acetyl-cis-khellactone (DOAcK), as well as its toxic potential. We obtained DOAcK with an enantiomeric excess of 70% by chemical synthesis. Our results showed that this compound exerts an important antidiabetic effect: blood glucose decreased in groups treated with DOAcK by 60.9% at dose of 15 mg/kg (p <0.05) compared with the diabetic control group, and demonstrated a statistically significant increase in weight gain (45.7 +/- 9.7 in the group treated with DOAcK vs. -23.0 +/- 33.1 in the group with diabetes). In a biochemical profile, DOAcK did not modify lipid metabolism and did not cause damage at the renal level. DOAcK administration increased the activities of Catalase (CAT), Glutathione Peroxidase (GPx), and Super Oxide Dismutase (SOD) to levels near those of the healthy group. Histopathological analysis exhibited morphology similar to that of the healthy group and the group treated with DOAcK. DOAcK is not mutagenic by Ames test for Salmonella typhimurium strains TA98, TA100, or TA102, and is not genotoxic by Micronucleus assay; median lethal dose (LD50) >2000 mg/kg and, at this dose, no signs of toxicity or death were reported after 14 days of observation. These results indicate that DOAcK can improve glucose metabolism, which may be due to the increased antioxidant activity of CAT, GPx and SOD. In addition, DOAcK is not toxic in the studies tested. (C) 2016 Elsevier Ltd. All rights reserved.
机译：吡喃香豆素是具有重要药理特性的化合物，例如抗炎，抗氧化剂，细胞毒性，抗病毒，抗菌和降血糖作用。这些分子作为用于治疗糖尿病（DM）的药用植物中的次生代谢产物而广泛存在。这项工作的目的是评估在链脲佐菌素（STZ）诱导的糖尿病大鼠中的抗糖尿病活性以及3'，4'-Di-O-乙酰基-顺式-甲壳酮（DOAcK）的抗氧化作用及其毒性潜力。通过化学合成，我们获得了对映体过量70％的DOAcK。我们的结果表明，该化合物具有重要的抗糖尿病作用：与糖尿病对照组相比，在以15 mg / kg的剂量进行DOAcK治疗的组中，血糖降低了60.9％（p <0.05），并且证明了体重的统计学显着增加增益（DOAcK治疗组为45.7 +/- 9.7，而糖尿病组为-23.0 +/- 33.1）。在生化特征中，DOAcK不会改变脂质代谢，也不会在肾脏水平引起损害。 DOAcK的施用将过氧化氢酶（CAT），谷胱甘肽过氧化物酶（GPx）和超氧化物歧化酶（SOD）的活性提高至接近健康组的水平。组织病理学分析显示出与健康组和DOAcK治疗组相似的形态。 DOAcK通过鼠伤寒沙门氏菌TA98，TA100或TA102的Ames试验没有致突变性，并且通过微核试验没有遗传毒性。中位数致死剂量（LD50）> 2000 mg / kg，在该剂量下，观察14天后未报告毒性或死亡迹象。这些结果表明DOAcK可以改善葡萄糖代谢，这可能是由于CAT，GPx和SOD的抗氧化活性增加。此外，DOAcK在所测试的研究中无毒。 （C）2016 Elsevier Ltd.保留所有权利。

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