Anaya-Eugenio Gerardo D, Rivero-Cruz Isabel, Rivera-Chávez José, Mata Rachel
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
J Ethnopharmacol. 2014 Aug 8;155(1):416-25. doi: 10.1016/j.jep.2014.05.051. Epub 2014 Jun 2.
Artemisia ludoviciana, commonly known as "estafiate", plays an important role in contemporary Mexico for treating several diseases including diabetes. To establish the preclinical efficacy of Artemisia ludoviciana as hypoglycemic and/or antihyperglycemic agent using well-known animal models.
Acute hypoglycemic as well as oral glucose (OGTT) and sucrose (OSTT) tolerance tests were used to demonstrate the value of the plant for treating diabetes. An essential oil (EO), an organic extract (OE) and an infusion (AE) were assayed in normal and NA-STZ-treated mice. The acute toxicity of the three preparations was analyzed by the Lorke method. The infusion was subjected to conventional phytochemical study using chromatographic conventional procedures. Some of the isolates were evaluated using the same pharmacological assays as well as an enzymatic test. The latter was employed to assess their potential inhibitory effect on yeast α-glucosidase.
Oral administration of OE to normal mice significantly decreased blood glucose level only at the dose of 100 mg/kg; in NA-STZ-mice the hypoglycemic effect was observed at the three doses tested (31.6, 100, and 316 mg/kg). The infusion reduced significantly, blood sugar levels only in diabetic mice; the best effect was observed at the dose of 316 mg/kg. The EO was inactive when evaluated in normal mice. Regarding to the antihyperglycemic effect, the best effect was observed with the OE, during the OGTT and OSTT in diabetic mice. The infusion (AE) showed better effects during the OGTT in both normal and diabetic animals at the dose of 100 mg/kg. Finally, the EO was inactive during an OGTT at the three doses tested (31.6, 100, and 316 mg/kg) in diabetic mice. In addition, the results of AE on the enzymatic test using yeast α-glucosidase revealed an inhibition of 45%; this finding was consistent with the results obtained with the same preparation in vivo during an OSTT. Conventional phytochemical analysis of the active AE led to the isolation and characterization of eupatilin (1), jaceosidin (2), arglanin (3), salvinine (4), and 3,5-dicaffeoylquinic acid (5). Biological testing of 1 and 3 revealed their hypoglycemic effect. The hypoglycemic effect of arglanin (3) was attenuated in the presence of nicorandil, which suggested that the lactone behaved as an ATP-K+-channel blocker as glibenclamide. Salvinine (4) turned out to be a mixed α-glucosidase inhibitor, while 3 was inactive.
Artemisia ludoviciana preparations showed hypoglycemic and antihyperglycemic effects, which could explain its effectiveness for treating diabetes in contemporary Mexico. Some of the active principles of the plant included compounds 1-5. These compounds seem to be acting synergistically on different molecular targets which involved glucose absorption and insulin liberation.
墨西哥艾菊,俗称“estafiate”,在当代墨西哥治疗包括糖尿病在内的多种疾病中发挥着重要作用。本研究旨在使用著名的动物模型确定墨西哥艾菊作为降血糖和/或抗高血糖药物的临床前疗效。
采用急性低血糖试验以及口服葡萄糖(OGTT)和蔗糖(OSTT)耐量试验来证明该植物治疗糖尿病的价值。对正常小鼠和链脲佐菌素(NA-STZ)处理的小鼠分别测定了精油(EO)、有机提取物(OE)和浸剂(AE)。采用洛克方法分析了这三种制剂的急性毒性。浸剂采用常规色谱法进行常规植物化学研究。部分分离物采用相同的药理试验以及酶试验进行评估。后者用于评估它们对酵母α-葡萄糖苷酶的潜在抑制作用。
给正常小鼠口服OE仅在100mg/kg剂量时显著降低血糖水平;在NA-STZ处理的小鼠中,在测试的三个剂量(31.6、100和316mg/kg)下均观察到降血糖作用。浸剂仅在糖尿病小鼠中显著降低血糖水平;在316mg/kg剂量时观察到最佳效果。在正常小鼠中评估时,EO无活性。关于抗高血糖作用,在糖尿病小鼠的OGTT和OSTT期间,OE观察到最佳效果。浸剂(AE)在100mg/kg剂量时,在正常和糖尿病动物的OGTT期间均显示出更好的效果。最后,在糖尿病小鼠中,EO在测试的三个剂量(31.6、100和316mg/kg)的OGTT期间均无活性。此外,AE对酵母α-葡萄糖苷酶的酶试验结果显示抑制率为45%;这一发现与在OSTT期间在体内用相同制剂获得的结果一致。对活性AE进行常规植物化学分析,分离并鉴定了灯盏乙素(1)、香叶木素(2)、紫菀苷(3)、鼠尾草酸(4)和3,5-二咖啡酰奎宁酸(5)。对1和3的生物学测试显示了它们的降血糖作用。在尼可地尔存在的情况下,紫菀苷(3)的降血糖作用减弱,这表明该内酯的作用类似于格列本脲,是一种ATP-K +通道阻滞剂。鼠尾草酸(4)原来是一种混合α-葡萄糖苷酶抑制剂,而3无活性。
墨西哥艾菊制剂显示出降血糖和抗高血糖作用,这可以解释其在当代墨西哥治疗糖尿病的有效性。该植物的一些活性成分包括化合物1-5。这些化合物似乎在涉及葡萄糖吸收和胰岛素释放的不同分子靶点上协同作用。