Nachar Abir, Saleem Ammar, Arnason John T, Haddad Pierre S
Natural Health Products and Metabolic Diseases Laboratory, Dept. of Pharmacology, Université de Montréal, Montreal, QC, Canada; Canadian Institutes of Health Research Team in Aboriginal Antidiabetic Medicines and Montreal Diabetes Research Center, Canada.
Canadian Institutes of Health Research Team in Aboriginal Antidiabetic Medicines and Montreal Diabetes Research Center, Canada; Laboratory for the Analysis of Natural and Synthetic Environmental Toxins, University of Ottawa, Ottawa, ON, Canada.
Phytochemistry. 2015 Sep;117:373-379. doi: 10.1016/j.phytochem.2015.07.001. Epub 2015 Jul 8.
In our previous study, Abies balsamea (L.) Mill., a plant used in Cree traditional medicine, had a strong effect on the regulation of glucose homeostasis in liver cells. This study aimed to isolate and identify its active constituents using a bioassay-guided fractionation approach as well as to elucidate their mechanism(s) of action. The effect of the crude extract and its constituents was evaluated on the activity of Glucose-6-Phosphatase (G6Pase) and Glycogen Synthase (GS) and phosphorylation of three kinases, AMP-activated protein kinase (AMPK), Akt and Glycogen Synthase Kinase-3 (GSK-3). Three compounds, abietic acid, dehydroabietic acid and squalene, were isolated from the most active fraction in the bioassays (hexane). The compounds were able to decrease the activity of G6Pase and to stimulate GS. Their effect on G6Pase activity involved both Akt and AMPK phosphorylation with significant correlations between insulin-dependent and -independent pathways and the bioassay. In addition, the compounds were able to stimulate GS through GSK-3 phosphorylation with a significant correlation between the signaling pathway and the bioassay. Dehydroabietic acid stood out for its strongest effect in all the experiments close to that of the crude extract. These compounds may have potential applications in the treatment of type 2 diabetes and insulin resistance.
在我们之前的研究中，加拿大香脂冷杉（Abies balsamea (L.) Mill.），一种克里族传统医学中使用的植物，对肝细胞葡萄糖稳态的调节有很强的作用。本研究旨在采用生物活性导向分离法分离和鉴定其活性成分，并阐明其作用机制。评估了粗提物及其成分对葡萄糖-6-磷酸酶（G6Pase）和糖原合酶（GS）活性以及三种激酶，即AMP活化蛋白激酶（AMPK）、Akt和糖原合酶激酶-3（GSK-3）磷酸化的影响。从生物测定中活性最高的部分（己烷）分离出三种化合物，即枞酸、脱氢枞酸和角鲨烯。这些化合物能够降低G6Pase的活性并刺激GS。它们对G6Pase活性的影响涉及Akt和AMPK的磷酸化，胰岛素依赖性和非依赖性途径与生物测定之间存在显著相关性。此外，这些化合物能够通过GSK-3磷酸化刺激GS，信号通路与生物测定之间存在显著相关性。脱氢枞酸在所有实验中表现出最强的作用，其效果与粗提物相近。这些化合物在2型糖尿病和胰岛素抵抗的治疗中可能具有潜在应用。
