Title Page
Contents
CHAPTER 1. A Literature Review 15
1.1. Coffee 15
1.1.1. Bioactive Components in Coffee 18
1.1.2. Changes in coffee constituents during roasting 28
1.2. Management of Diabetes 31
1.2.1. Mechanism of action of antihyperglycemic agents 33
1.2.2. Adverse events 35
1.2.3. Complications of Diabetes Mellitus 35
1.2.4. Management of postprandial hyperglycemia in type 2 diabetes 36
1.3. Objective of the study 41
CHAPTER 2. Comparisons of Anti-hyperglycemic Effects of 3 Different Coffee Varieties in-vitro and in-vivo animal Model 45
Abstract 46
2.1. Introduction 48
2.2. Material and methods 51
2.2.1. Extraction 51
2.2.2. Total Phenolic Content Analysis 51
2.2.3. Rat α-glucosidase Inhibition Assay 52
2.2.4. Porcine α-amylase Inhibition Assay 53
2.2.5. Sucrose, Maltase and Glucoamylase Inhibition Assay 53
2.2.6. In-vivo Animal Model 54
2.2.7. Blood Analysis 55
2.2.8. Statistical analysis 55
2.3. Results and Discussions 56
2.3.1. Total phenolic contents and HPLC analysis of the extracts in roasted coffee extracts 56
2.3.2. α-Glucosidase Inhibitory Activity 58
2.3.3. α-Amylase Inhibition assay 64
2.3.4. Sucrase, Maltase, and Glucoamylase Inhibition Assay 64
2.3.5. Blood glucose-lowering effect of coffee extracts in vivo 73
2.3.6. Pharmacodynamics Parameters 79
2.4. Conclusions 82
CHAPTER 3. Antihyperglycemic and Antioxidant Effects of Coffee Roasting Degree on In-vitro and In-vivo Animal Models 83
Abstract 84
3.1. Introduction 87
3.2. Materials and Methods 90
3.2.1. Extraction 90
3.2.2. Total Phenolic Content Analysis 91
3.2.3. Rat α-glucosidase Inhibition Assay 92
3.2.3. Porcine α-amylase Inhibition Assay 93
3.2.4. Sucrose, Maltase and Glucoamylase Inhibition Assay 94
3.2.5. In-vivo Animal Model 95
3.2.6. Blood Analysis 95
3.2.7. Statistical analysis 96
3.3. Result and Discussion 97
3.3.1. Total phenolic contents (TPC) 97
3.3.2. In vitro antioxidant capacity by ORAC system 101
3.3.3. α-glucosidase Inhibitory activities 103
3.3.4. α-amylase inhibition assay 106
3.3.5. Sucrase, Maltase and Glucoamylase Inhibitory Activities 108
3.3.6. Sucrose loading test in SD Rat and db/db mice model 114
3.4. Conclusions 121
CHAPTER 4. α-Glucosidases and α-Amylase Inhibitory Effects of Caffeic of Caffeic Acid and In-Chlorogenic Acid In-vivo and In-vitro animal models 122
Abstract 123
4.1. Introduction 125
4.2. Material and Methods 129
4.2.1. Chemicals 129
4.2.2. High Performance Liquid Chromatography (HPLC) Analysis of CGA and Caffeic acid 129
4.2.3. Total Phenolic Content Analysis 130
4.2.4. Rat α-glucosidase Inhibition Assay 131
4.2.5. Porcine α-amylase Inhibition Assay 132
4.2.6. Sucrose, Maltase and Glucoamylase Inhibition Assay 133
4.2.7. In-vivo Animal Model 134
4.2.8. Blood Analysis 134
4.2.9. Statistical analysis 135
4.3. Results and Discussions 136
4.3.1. α-glucosidase inhibitory activities of caffeic acid and CGA 136
4.3.2. α-amylase inhibitory activities of caffeic acid and CGA 138
4.3.3. Sucrase, Maltase and Glucoamylase inhibitory activities 140
4.3.4. Comparison of the amounts of chlorogenic acid, caffeic acid in roasted coffee extracts 145
4.3.5. In vivo blood glucose lowering experiment 147
4.4. Conclusions 153
REFERENCES 154
ABSTRACT 171
Table 1. Chemical composition of green Coffea arabica and Coffea canephora seeds. 27
Table 2. Roasting Degrees of Coffee Beans 30
Table 3. The half-maximal inhibitory concentration (IC50) values for rat intestinal α-glucosidase by water extracted coffee types 59
Table 4. The half-maximal inhibitory concentration (IC50) values for rat intestinal α-glucosidase by ethyl alcohol extracted coffee types[이미지참조] 60
Table 5. Half maximal inhibitory concentration (IC50) of coffee water (DW) extract and ethyl alcohol extract on rat small intestinal sucrase,... 72
Table 6. Changes in pharmacodynamics (PD) parameters of control and after administration of GWE, EWE, SWE, and acarbose with sucrose or... 80
Table 7. Changes in pharmacodynamics (PD) parameters of control and after administration of GEE, EEE, SEE and acarbose with sucrose or... 81
Table 8. Total phenolic content of roasted coffee extracts 100
Table 9. Comparison of inhibitory activities (IC50) of caffeic acid (mg/mL) and CGA (mg/mL) against α-glucosidase, α-amylase, sucrase,...[이미지참조] 144
Table 10. Comparison of the amounts of chlorogenic acid, caffeic acid 146
Figure 1. Layers in a coffee fruit 17
Figure 2. The main chlorogenic acids in coffee beans. 22
Figure 3. Chemical structure of chlorogenic acid and caffeic acid 26
Figure 4. Age standardized prevalence of type 2 diabetes and impaired glucose tolerance 32
Figure 5. Mechanism of action of α-glucosidase inhibitors 34
Figure 6. chemical structure of synthetic α-glucosidase inhibitors 39
Figure 7. Acarbose mechanism of action: competitive inhibition of the intestinal enzymatic hydrolysis of oligosaccharides 40
Figure 8. Total phenolic content (mg GAE/g sample) 57
Figure 9. Dose dependent changes in rat intestinal α-glucosidase inhibitory activity (%inhibition) of water extracted coffee types (p 〈 0.05... 61
Figure 10. Dose dependent changes in rat intestinal α-glucosidase inhibitory activity (%inhibition) of ethyl alcohol extracted coffee types at... 63
Figure 11. Dose dependent changes in rat intestinal sucrase of water extracted coffee... 65
Figure 12. Dose dependent changes in rat intestinal sucrase of ethyl alcohol extracted coffee... 66
Figure 13. Dose dependent changes in rat intestinal maltase of water extracted coffee... 67
Figure 14. Dose dependent changes in rat intestinal maltase of ethyl alcohol extracted coffee... 68
Figure 15. Dose dependent changes in rat intestinal glucoamylase of water extracted coffee... 69
Figure 16. Dose dependent changes in rat intestinal glucoamylase of ethyl alcohol extracted coffee... 70
Figure 17. Effect of coffee of water extracts on sucrose loading test After fasting for 24 hours, 4-week-old, male SD rats were orally... 75
Figure 18. Effect of coffee of ethyl alcohol extracts on sucrose loading test... 76
Figure 19. Effect of coffee of water extracts on starch loading test After fasting for 24 hours, 4-week-old, male SD rats were orally... 77
Figure 20. Effect of coffee of ethyl alcohol extracts on starch loading test After fasting for 24 hours, 4-week-old, male SD rats were orally... 78
Figure 21. Total phenolic content of roasted coffee extracts. 99
Figure 22. Antioxidant activities of coffee extracts based on ORAC assay 102
Figure 23. Dose dependent changes in rat intestinal α-glucosidase inhibitory activity (% inhibition) of roasting coffee extracts.... 105
Figure 24. Dose dependent changes in rat intestinal α-amylase inhibitory activity (% inhibition) of Roasting coffee extracts. 107
Figure 25. Dose dependent changes in rat intestinal sucrase inhibitory activity (% inhibition) of roasted coffee extracts.... 110
Figure 26. Dose dependent changes in rat intestinal Maltase inhibitory activity (% inhibition) of roasted coffee extracts.... 111
Figure 27. Dose dependent changes in rat intestinal glucoamylase inhibitory activity (% inhibition) of roasted coffee extracts. p 〈 0.05 by... 113
Figure 28. Effect of roasted coffee extracts on sucrose loading test. After fasting for 24 h, 5-week-old, male SD rats were orally administered... 116
Figure 29. Effect of roasted coffee extracts on sucrose loading test. After fasting for 24 h, 5-week-old, male SD rats were orally administered... 117
Figure 30. Effect of roasted coffee extracts on starch loading test. After fasting for 24 h, 5-week-old, male SD rats were orally administered... 119
Figure 31. Effect of roasted coffee extracts on starch loading test. After fasting for 24 h, 5-week-old, male SD rats were orally administered... 120
Figure 32. Dose dependent changes in rat intestinal α-glucosidase inhibitory activity (% inhibition) of caffeic and chlorogenic acids.... 137
Figure 33. Dose dependent changes in rat intestinal α-amylase inhibitory activity (% inhibition) of caffeic acid and chlorogenic acid.... 139
Figure 34. Dose dependent changes in rat intestinal sucrase inhibitory activity (% inhibition) of caffeic and chlorogenic acids. 141
Figure 35. Dose dependent changes in rat intestinal Maltase inhibitory activity (% inhibition) of caffeic and chlorogenic acids... 142
Figure 36. Dose dependent changes in rat intestinal Glucoamylase inhibitory activity (% inhibition) of caffeic and chlorogenic acids... 143
Figure 37. Blood glucose lowering effect of chlorogenic acid in sucrose loading test.... 148
Figure 38. Blood glucose lowering effect of caffeic acid on sucrose loading test.... 150
Figure 39. Blood glucose lowering effect of chlorogenic acid in starch loading test.... 151
Figure 40. Blood glucose lowering effect of caffeic acid in starch loading test.... 152