报 告 人：李水盛（台湾大学药学研究所教授）
报告题目：Exploration of α-glucosidase inhibitors from Machilus philippineses and Syagrus romanzoffiana（两种植物中a-葡萄糖酶抑制剂的研究）
报告摘要：Several strategies to monitor the blood glucose for type II diabetes mellitus have been approached. One of them is to inhibit or reduce the production of glucose from the small intestine. Thus, the inhibitors of α-glucosidase, which exists in the small intestine brush border, will interfere the digestion of carbohydrates, leading to better glycemic control and beneficial to the therapy of type II diabetes. During past seven years, we had screened the extracts of the higher plants against α-glucosidase type IV from Bacillus stearothermophilus. Several extracts were found to be active (>50% inhibition) at 100 μg/ml level. Among them, the CH2Cl2- soluble fraction of the leaves of 菲律賓楠Machilus philippinensis Merr. (Lauraceae) (93.7% inhibition) and the n-BuOH soluble fraction of the seeds of 皇后葵Syagrus romanzoffiana (Cham.) Glassman (Arecaceae) (73% inhibition) were chosen for further clarification of their active constituents.
Following the bioassay guided approach, two active compounds with the IC50 values of 6.1 and 1.0 μM, respectively, were isolated from M. philippinensis by general chromatographic methods. The active constituents in some subfractions were relatively complicated, as observed from HPLC analysis, and couldn’t be separated neatly by common methods. Thus, we applied the high performance liquid chromatography- solid phase extraction- nuclear magnetic resonance (HPLC-SPE-NMR) hyphenated technique to solve the problems encountered in separation and structural elucidation. Such approach resulted in the identification of eight additional compounds, seven of which are 3-O-(coumaroyl-rhamnopyranosyl)-flavonols whose structures are interchangeable through trans-esterification mechanism during longer exposure in the delivery system. Four of the compounds identified are new natural products.
Using similar approaches, fourteen active compounds were isolated from the seeds of S. romanzoffiana. Five of ten stilbenoids isolated are new and are potent against the title enzyme. Application of LC-SPE-NMR led to the identification of two additional new stilbenoids besides the known scirpusin B. The in vivo assay on normal Wistar rats using oral sucrose challenge was undertaken for the abundant compounds and found 3,3’,4,5,5’-pentahydroxy-trans-stilbene and kompasinol to be active in reducing the postprandial blood glucose level.
In this occasion, the details of the study design, approaches including sample handling for HPLC-SPE-NMR analysis, and structural characterization will be presented.