Domínguez-Mendoza Elix Alberto, Cornejo-Garrido Jorge, Burgueño-Tapia Eleuterio, Ordaz-Pichardo Cynthia
Laboratorio de Biología Celular y Productos Naturales, Edificio de Posgrado, Primer Piso, Escuela Nacional de Medicina y Homeopatía (ENMH), Instituto Politécnico Nacional, Guillermo Massieu Helguera 239, Col. La Escalera Del. Gustavo A. Madero, 07320 CDMX, Mexico.
Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas (ENCB), Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala s/n, Col. Santo Tomás, 11340 CDMX, Mexico.
Bioorg Med Chem Lett. 2016 Aug 15;26(16):4086-91. doi: 10.1016/j.bmcl.2016.06.071. Epub 2016 Jun 25.
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 15mg/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) >2000mg/kg and, at this dose, no signs of toxicity or death were reported after 14days 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.
吡喃香豆素是一类具有重要药理特性的化合物，如抗炎、抗氧化、细胞毒性、抗病毒、抗菌和降血糖作用。这些分子作为次生代谢产物广泛存在于用于治疗糖尿病（DM）的药用植物中。本研究的目的是评估3',4'-二-O-乙酰基-顺式凯刺酮（DOAcK）对链脲佐菌素（STZ）诱导的糖尿病大鼠的抗糖尿病活性、抗氧化作用及其潜在毒性。我们通过化学合成获得了对映体过量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，DOAcK治疗组在15mg/kg剂量下血糖降低了60.9%（p<0.05），并且体重增加具有统计学意义（DOAcK治疗组为45.7±9.7，糖尿病组为-23.0±33.1）。在生化指标方面，DOAcK未改变脂质代谢，也未对肾脏造成损害。给予DOAcK可使过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）和超氧化物歧化酶（SOD）的活性增加至接近健康组的水平。组织病理学分析显示其形态与健康组和DOAcK治疗组相似。DOAcK对鼠伤寒沙门氏菌TA98、TA100或TA102菌株的Ames试验无致突变性，微核试验也无遗传毒性；半数致死剂量（LD50）>2000mg/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的抗氧化活性增加所致。此外，在本研究测试中DOAcK无毒。
