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

DC FieldValueLanguage
dc.contributor.advisor성상현-
dc.contributor.authorDong Young Lee-
dc.date.accessioned2017-07-13T16:40:51Z-
dc.date.available2017-07-13T16:40:51Z-
dc.date.issued2017-
dc.identifier.other000000142390-
dc.identifier.urihttp://hdl.handle.net/10371/120168-
dc.description학위논문 (박사)-- 서울대학교 대학원 : 약학과, 2017. 2. 성상현.-
dc.description.abstractType 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 Baker’s 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 Baker’s 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 their inhibitory activity against rat intestinal α-glucosidase, porcine pancreatic α-amylase, and PTP-1B. In the case of rat intestinal α-glucosidase and porcine pancreatic α-amylase, compound 8 showed the potent inhibitory activity (IC50 17.3 and 13.4 μM, respectively) which was comparable to the positive control, acarbose. In the case of PTP-1B, compounds 8 and 60 exhibitied the most significant inhibitory activities (IC50 2.0 and 10.3 μM, respectively) among the hydrolysable tannins and polyhydroxytriterpene derivatives, respectively.-
dc.description.tableofcontentsI. Introduction 1 II. Materials and Methods 14 1. Materials 14 1.1. Plant material 14 1.2. Reagents for isolation and purification 15 1.3. Reagents for in vitro enzyme assay 15 1.4. Equipments 15 2. Methods 18 2.1. Extraction and fractionation of T. chebula 18 2.2. HPLC-based activity profiling of T. chebula 19 2.3. Targeted Isolation of Bakers yeast α-glucosidase inhibitory compounds from B2 and B3 fraction of T. chebula 20 2.4. Further isolation of constituents of T. chebula 35 2.5. General partial hydrolysis and acid hydrolysis 93 2.6. Determination of absolute configuration of sugar 94 2.7. Evaluation of Bakers yeast α-glucosidase inhibitory activity 95 2.8. Evaluation of rat intestinal α-glucosidase inhibitory activity 95 2.9. Evaluation of porcine pancreatic α-amylase inhibitory activity 96 2.10. Evaluation of protein-tyrosine phosphatase 1B (PTP-1B) inhibitory activity 97 III. Result and discussion 98 1. Tracking α-glucosidase inhibitory constituents from T. chebula fruits with HPLC-based activity profiling 98 2. Elucidation of chemical structures of isolated compounds from T. chebula with HPLC-based activity profiling. 104 2.1. Compound 1 104 2.2. Compound 2 105 2.3. Compound 3 106 2.4. Compound 4 110 2.5. Compounds 5 and 6 111 2.6. Compound 7 113 2.7. Compound 8 115 2.8. Compounds 9-11 116 2.9. Compounds 12 and 13 121 3. Elucidation of chemical structures of further isolated compounds from T. chebula. 129 3.1. Compounds 14 and 15 129 3.2. Compounds 16 and 17 130 3.3. Compound 18 132 3.4. Compounds 19-21 136 3.5. Compounds 22-24 142 3.6. Compound 25 149 3.7. Compound 26 150 3.8. Compounds 27 and 28 151 3.9. Compounds 29 and 30 153 3.10. Compounds 31-33 154 3.11. Compounds 34-37 157 3.12. Compounds 38a and 38b 161 3.13. Compound 39 162 3.14. Compound 40 163 3.15. Compound 41 164 3.16. Compounds 42 and 43 165 3.17. Compounds 44 and 45 167 3.18. Compounds 46 and 47 169 3.19. Compounds 48 and 49 171 3.20. Compounds 50-55 173 3.21. Compounds 56 and 57 184 3.22. Compounds 58-61 186 3.23. Compounds 62 and 63 191 3.24. Compound 64 192 3.25. Compounds 65 and 66 194 4. Inhibitory activities of compounds from T. chebula against Bakers yeast α-glucosidase, rat intestinal α-glucosidase, porcine pancreatic α-amylase, and PTP-1B. 200 IV. Conclusion 209 V. References 211 국문초록 226-
dc.formatapplication/pdf-
dc.format.extent10380351 bytes-
dc.format.mediumapplication/pdf-
dc.languageeng-
dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subjectTerminalia chebula-
dc.subjectCombretaceae-
dc.subjecthydrolysable tannin-
dc.subjectpolyhydroxytriterpene-
dc.subjectHPLC-based activity profiling-
dc.subject.ddc615-
dc.titleα-Glucosidase Inhibitory Constituents from Terminalia chebula Fruits-
dc.title.alternative가자나무 열매에서 분리한 알파 글루코시데이즈 억제 성분-
dc.typeThesis-
dc.contributor.AlternativeAuthor이동영-
dc.description.degreeDoctor-
dc.citation.pagesxv, 230-
dc.contributor.affiliation약학대학 약학과-
dc.date.awarded2017. 2-
Appears in Collections:
College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Theses (Ph.D. / Sc.D._약학과)
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