α-Glucosidase Inhibitory Constituents from Terminalia chebula Fruits ; 가자나무 열매에서 분리한 알파 글루코시데이즈 억제 성분

학위논문 (박사)-- 서울대학교 대학원 : 약학과, 2017. 2. 성상현. ; Type 2 diabetes mellitus (T2DM), known as non-insulin-independent diabetes, is a chronic metabolic disorder which is due to insulin-resistance in the tissues. As a result, insulin resistance leads to elevated blood glucose levels, which can damage many of the organs. One of the therapeutic approaches for treating T2DM is to alleviate postprandial hyperglycemia. This is achieved by suppressing the glucose absorption from the gut by inhibiting intestinal carbohydrate digesting enzymes such as α-glucosidase. In this study, to isolate new α-glucosidase inhibitory compounds efficiently, an HPLC-based activity profiling with dereplication was carried out. HPLC-based activity profiling of an extract from Terminalia chebula fruits enabled the isolation and identification of thirteen compounds including four new ones (3 and 11-13). Among the thirteen compounds, compounds 4-13 obtained from the active microfractions exhibited potent inhibitory activities against Bakers yeast α-glucosidase. These results confirm that HPLC-based activity profiling is an effective method for isolating new bioactive compounds. Moreover, to investigate the constituents of T. chebula fruits, further isolation was carried out. As a result, fifty-three compounds including thirty-six hydrolysable tannins and seventeen polyhydroxytriterpenes were further isolated from a methanolic extract of T. chebula fruits. A total of sixty-six compounds, including nine new hydrolysable tannins (3, 11-13, 18, 20, 21, 23, and 24) and three new polyhydroxytriterpene derivatives (51, 52, and 66), were finally isolated and identified. The inhibitory activities of all the isolated compounds against Bakers yeast α-glucosidase were tested, and as a result, twenty-four compounds (4-13, 16-18, 22, 25, 43-49, 60, and 61) exhibited inhibitory activities. Among these compounds, compounds 8, 11, and 12 showed significant inhibitory activity (IC50 8.3, 6.4, and 2.9 μM, respectively). Furthermore, all the compounds were tested for ...