Govorko Dmitry, Logendra Sithes, Wang Yanxin, Esposito Debora, Komarnytsky Slavko, Ribnicky David, Poulev Alexander, Wang Zhong, Cefalu William T, Raskin Ilya
Rutgers University, Biotech Center, 59 Dudley Road, New Brunswick, NJ 08901, USA.
Am J Physiol Endocrinol Metab. 2007 Dec;293(6):E1503-10. doi: 10.1152/ajpendo.00420.2007. Epub 2007 Sep 11.
An ethanolic extract of Russian tarragon, Artemisia dracunculus L., with antihyperglycemic activity in animal models was reported to decrease phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression in STZ-induced diabetic rats. A quantitative polymerase chain reaction (qPCR) assay was developed for the bioactivity-guided purification of the compounds within the extract that decrease PEPCK expression. The assay was based on the inhibition of dexamethasone-stimulated PEPCK upregulation in an H4IIE hepatoma cell line. Two polyphenolic compounds that inhibited PEPCK mRNA levels were isolated and identified as 6-demethoxycapillarisin and 2',4'-dihydroxy-4-methoxydihydrochalcone with IC(50) values of 43 and 61 muM, respectively. The phosphoinositide-3 kinase (PI3K) inhibitor LY-294002 showed that 6-demethoxycapillarisin exerts its effect through the activation of the PI3K pathway, similarly to insulin. The effect of 2',4'-dihydroxy-4-methoxydihydrochalcone is not regulated by PI3K and dependent on activation of AMPK pathway. These results indicate that the isolated compounds may be responsible for much of the glucose-lowering activity of the Artemisia dracunculus extract.
据报道，俄罗斯龙蒿（Artemisia dracunculus L.）的乙醇提取物在动物模型中具有降血糖活性，可降低链脲佐菌素诱导的糖尿病大鼠中磷酸烯醇丙酮酸羧激酶（PEPCK）的mRNA表达。开发了一种定量聚合酶链反应（qPCR）检测方法，用于对提取物中降低PEPCK表达的化合物进行生物活性导向纯化。该检测基于对H4IIE肝癌细胞系中地塞米松刺激的PEPCK上调的抑制作用。分离并鉴定出两种抑制PEPCK mRNA水平的多酚化合物，分别为6-去甲氧基毛蒿素和2',4'-二羟基-4-甲氧基二氢查耳酮，其IC(50)值分别为43和61 μM。磷酸肌醇-3激酶（PI3K）抑制剂LY-294002表明，6-去甲氧基毛蒿素与胰岛素类似，通过激活PI3K途径发挥作用。2',4'-二羟基-4-甲氧基二氢查耳酮的作用不受PI3K调节，且依赖于AMPK途径的激活。这些结果表明，分离出的化合物可能是龙蒿提取物大部分降糖活性的原因。
