Chi Tzong-Cherng, Lee Shoei-Sheng, Su Ming-Jai
Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Planta Med. 2006 Oct;72(13):1175-80. doi: 10.1055/s-2006-947199. Epub 2006 Aug 21.
The antihyperglycemic actions of some aporphines and their derivatives in normal Wistar, streptozotocin (STZ)-induced diabetic (IDDM) and nicotinamide-STZ induced diabetic (NIDDM) rats were investigated in this study. These compounds included thaliporphine, glaucine, boldine, N-methyllaurotetanine, and predicentrine and the derivatives, N-[2-(2-methoxyphenoxy)ethyl]norglaucine and diacetyl- N-allylsecoboldine. Bolus intravenous injection of these compounds decreased the plasma glucose levels in a dose-dependent manner in both normal and diabetic rats. Among them, thaliporphine was found to have the most potent antihyperglycemic effect in both NIDDM and IDDM diabetic rats. It was found that thaliporphine could stimulate the release of insulin in both normal and diabetic rats, and a dose of 1 mg per kg thaliporphine could significantly attenuate the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. Similar treatment with thaliporphine significantly increased the skeletal muscle glycogen synthesis in both normal and diabetic rats. Hence, the hypoglycemic effect of thaliporphine in diabetic rats could be attributed to the stimulation of insulin release and the increase of glucose utilization.
本研究考察了某些阿朴啡及其衍生物对正常Wistar大鼠、链脲佐菌素（STZ）诱导的糖尿病（IDDM）大鼠和烟酰胺-链脲佐菌素诱导的糖尿病（NIDDM）大鼠的降血糖作用。这些化合物包括去甲紫堇碱、青藤碱、波尔定碱、N-甲基劳丹碱、前胡碱及其衍生物N-[2-(2-甲氧基苯氧基)乙基]去甲青藤碱和二乙酰-N-烯丙基去甲波尔定碱。静脉推注这些化合物可使正常大鼠和糖尿病大鼠的血糖水平呈剂量依赖性降低。其中，去甲紫堇碱在NIDDM和IDDM糖尿病大鼠中均具有最强的降血糖作用。研究发现，去甲紫堇碱可刺激正常大鼠和糖尿病大鼠胰岛素的释放，每千克体重1毫克的去甲紫堇碱剂量可显著减轻正常大鼠静脉葡萄糖耐量试验诱导的血糖升高。用去甲紫堇碱进行类似处理可显著增加正常大鼠和糖尿病大鼠骨骼肌糖原的合成。因此，去甲紫堇碱对糖尿病大鼠的降血糖作用可能归因于刺激胰岛素释放和增加葡萄糖利用。
