Medicinal Foods as Potential Therapies for Type-2 Diabetes and Associated Diseases: The Chemical and Pharmacological Basis of their Action

Cover......Page 1
MEDICINAL FOODS
AS POTENTIAL
THERAPIES FOR
TYPE-2 DIABETES
AND ASSOCIATED
DISEASES:
The Chemical and Pharmacological
Basis of their Action
......Page 3
Copyright......Page 4
About the Author......Page 5
Preface......Page 6
Acknowledgements......Page 10
Section A: Type-2 diabetes: Prevalence and significance
......Page 11
Diabetes......Page 12
Classification of diabetes......Page 13
Diagnosis criteria: Diabetic and prediabetic conditions......Page 14
Global prevalence of diabetes......Page 16
The social and economic impact of diabetes......Page 18
Further reading......Page 19
Section B: Normal physiological control of carbohydrate and lipid metabolism and some common antidiabetic therapeutic targets
......Page 20
Introduction......Page 21
Carbohydrate digestion......Page 22
Mechanisms of glucose uptake and transport......Page 24
Glycogenesis......Page 26
Glycogenolysis......Page 28
Gluconeogenesis......Page 30
Hormonal regulation of glucose metabolism......Page 34
Production and release......Page 36
Mechanism of insulin action......Page 39
Glucagon and related peptides......Page 41
Incretins......Page 43
The AMP-activated protein kinase (AMPK) and cellular energy balance regulation......Page 45
References......Page 46
Overview of lipids chemistry......Page 48
Triacylglycerols or triglycerides (TGs)......Page 49
Cholesterol and steroids......Page 51
Lipid digestion......Page 56
Lipid uptake from the intestine and transport system......Page 58
Utilization of lipids as an energy source......Page 62
De novo fatty acid synthesis......Page 67
Hormonal control of lipid metabolism......Page 69
Summary of energy homeostasis and hormonal control......Page 71
References......Page 72
Section C: Pathophysiology of type 2 diabetes and therapeutic options
......Page 73
Acute emergencies......Page 74
Microvascular or microangiopathic damage of the capillaries......Page 75
Diabetic neuropathy......Page 78
Diabetic nephropathy......Page 79
The diabetic foot ulcer and amputation......Page 80
T2D and advanced glycated end products (AGEs)......Page 81
Oxidative stress in T2D pathology......Page 84
The NAD(P)H oxidase system in T2D......Page 85
The mitochondrial respiratory system......Page 86
Antioxidant defences......Page 87
Low-grade inflammation as a link between obesity and T2D......Page 89
References......Page 92
Type 2 diabetes diagnosis and management by lifestyle change......Page 94
Pharmacological management approach for T2D......Page 95
Biguanides......Page 97
GLP-1 receptor agonists and DPP-4 inhibitors......Page 100
Exenatide......Page 101
Dipeptidyl peptidase-4 (DPP-4) inhibitors......Page 102
The sodium-glucose cotransporter-2 (SGL2) inhibitors......Page 103
Sulfonylureas......Page 104
Thiazolidinedione (TZD) or glitazones......Page 106
Insulin......Page 109
Other antidiabetic drugs of choice......Page 110
Further readings......Page 111
The what and why of secondary plant metabolites......Page 113
General overview of secondary metabolites biosynthesis......Page 114
The terpenoids biosynthesis pathway......Page 115
The shikimate biosynthesis pathway......Page 123
The flavonoids (mixed shikimate and acetate) biosynthesis pathway......Page 128
Alkaloids......Page 131
Pharmacological principles of drugs action-How do plant food metabolites act?......Page 132
References......Page 135
Section D: Potential modulators of type-2 diabetes and associated diseases: Super fruits
......Page 137
Botanical and taxonomic perspectives......Page 138
Common usage and production......Page 140
Anthocyanins and anthocyanidins......Page 141
Other polyphenol constituents of bilberries and blueberries......Page 147
Bioavailability and pharmacokinetic profile......Page 149
Data from in vitro studies......Page 150
Antidiabetic and antiobesity potential assessments in animal models......Page 155
Human trials......Page 158
Bilberries/blueberries and diabetes retinopathy......Page 162
Antioxidant effect......Page 164
Anti-inflammatory effects......Page 166
Modulation of the insulin signal transduction pathways......Page 167
Conclusion......Page 168
References......Page 169
Further reading......Page 177
8
The chemical and pharmacological basis of bitter melon (Momordica charantia L.) as a potential therapy for typ .........Page 179
Introduction to the plant-Bitter melon......Page 180
Taxonomic and botanical considerations......Page 182
The chemistry of bitter melon......Page 183
Macro- and micronutrients......Page 184
Carotenoids and fatty acids......Page 185
Phenolic constituents......Page 189
Essential oils......Page 191
Cucurubitane-type triterpenes......Page 192
Oleane-type and other triterpenes......Page 210
Alkaloids......Page 213
Antidiabetic, antiobesity and lipid lowering effects of bitter melon......Page 214
Potentially active antidiabetic and/or antiobesity principles of bitter melon......Page 218
Effect on insulin secretion and signalling pathways......Page 220
Carbohydrate digestion and/or absorption......Page 229
Glucose metabolism in the liver......Page 230
Anti-inflammatory mechanisms......Page 231
Antioxidant effects......Page 234
Organ protection......Page 236
Other mechanisms and further active constituents......Page 237
Clinical trials......Page 238
Potential toxic and other undesirable effects......Page 240
References......Page 241
Further reading......Page 251
9
The chemical and pharmacological basis of guava (Psidium guajava L.) as potential therapy for type 2 diabetes  .........Page 252
Botanical description and taxonomy......Page 253
Guava utilization as food and medicine......Page 254
Nutritional perspective......Page 255
Phenolic acids and related compounds......Page 257
Flavonoids......Page 258
Unusual phenolics and tannins......Page 265
Essential oils and other non-phenolic components......Page 268
Triterpenes......Page 272
The pharmacology of guava fruits in diabetes and associated diseases......Page 277
The pharmacology of guava leaves in diabetes and associated diseases......Page 283
Modulation of insulin and other signaling molecules related to glycaemic and lipid control......Page 285
Antioxidant mechanism......Page 289
Anti-inflammatory mechanisms......Page 290
Effects on carbohydrate digestion or absorption......Page 291
Other mechanisms......Page 293
Cardiovascular effects: Cardiac hypertrophy and hypertension......Page 294
Wound healing effects......Page 296
Overview of the guava antidiabetic principles......Page 297
Clinical studies......Page 298
References......Page 299
Further reading......Page 306
Introduction to Abelmoschus esculentus (L.) Moench......Page 307
Botanical and taxonomic considerations......Page 308
Economic significance......Page 311
Seed oil......Page 313
Non-oil components......Page 315
Polysaccharide components......Page 318
Effects of okra extracts and purified compounds on diabetes and associated diseases......Page 319
Organoprotective and other effects......Page 327
Toxicity......Page 328
References......Page 329
Further reading......Page 332
11
The chemical and pharmacological basis of papaya (Carica papaya L.) as potential therapy for type-2 diabetes......Page 333
Botanical and taxonomic considerations......Page 334
Extent of papaya fruits production/utilisation......Page 337
Uses as food and medicine......Page 340
Nutritional composition......Page 341
Phenolic acids and flavonoids derivatives......Page 342
Isothiocyanates and related compounds......Page 344
Alkaloids......Page 345
Enzymes and protein components......Page 346
In vitro studies......Page 347
Antidiabetic and lipid lowering effects in animal models......Page 349
Papaya and wound healing......Page 352
Antihypertensive effect......Page 355
Evidence of efficacy from human trials......Page 356
Conclusion......Page 358
References......Page 359
Further reading......Page 363
12
The chemical and pharmacological basis of pomegranate (Punica grantum L.) as potential therapy for type-2&sp......Page 364
Botany and taxonomy......Page 365
Uses as food and medicine......Page 369
The chemistry of pomegranate......Page 371
Phenolic acids and related compounds......Page 372
Flavonoids......Page 375
Tannins......Page 381
Lignans......Page 389
Seed oil......Page 390
Other compounds......Page 392
Evidence of efficacy from in vitro and in vivo studies......Page 393
General anti-inflammatory effects......Page 401
Fruits......Page 404
Flowers......Page 408
Seed oil and punicic acid......Page 411
Leaves......Page 413
Evidence of efficacy from clinical studies......Page 414
Pharmacokinetics and toxicological perspectives......Page 418
General summary and conclusion......Page 419
References......Page 421
Further reading......Page 431
13
The chemical and pharmacological basis of prickly pear cactus (Opuntia species) as potential therapy for type .........Page 433
Taxonomic and botanical perspectives......Page 434
Food production......Page 439
The chemistry of cactus pears......Page 441
Betalains......Page 442
Polyphenols......Page 443
Seeds oil......Page 447
Polysaccharides components......Page 448
Antidiabetic effect demonstrated through animal studies......Page 449
Antiobesity and lipid lowering potential......Page 451
Antioxidant effects......Page 453
Anti-inflammatory mechanisms......Page 455
Polysaccharides......Page 456
Antioxidant effects of indicaxanthin and betanin......Page 457
Antidiabetic effects of cactus pear pigments......Page 459
Other compounds......Page 460
Diuretic effects......Page 461
Human studies on prickly pears......Page 462
General summary and conclusions......Page 463
References......Page 464
Further reading......Page 470
Introduction......Page 471
Botanical and taxonomic perspectives......Page 473
Ornamental, food, and medicinal values......Page 475
Antidiabetic effects in animals models......Page 477
Chemical components of C. pepo......Page 478
Polyphenols......Page 479
Terpenoids......Page 480
Tocopherols......Page 482
Polysaccharides......Page 484
Antidiabetic effect of C. moschata......Page 485
Antidiabetic effects of C. ficifolia......Page 491
Antidiabetic effect of C. maxima......Page 493
Conclusions......Page 495
References......Page 496
Further reading......Page 500
Section E: Potential modulators of type-2 diabetes and associated diseases: Spices
......Page 501
14
The chemical and pharmacological basis of cinnamon (Cinnamomum species) as potential therapy for type-2&spi1......Page 502
Introduction......Page 503
Taxonomic and botanical descriptions......Page 504
Medicinal uses......Page 507
The chemistry of the cinnamon bark......Page 508
Volatile components......Page 509
Non-volatile components......Page 511
General pharmacology......Page 516
Evidence of efficacy from studies on animal models: Cinnamon powder and crude extracts......Page 518
Glucose production......Page 520
Gene and protein expression/activation......Page 521
Antioxidant and antiglycation effects......Page 523
Cinnamaldehyde......Page 525
Cinnamaldehyde and glycaemic control......Page 526
Antiobesity and lipid lowering effects......Page 527
Polar and phenolic components as active principles......Page 529
Evidence of efficacy from human trials......Page 531
Other pharmacological effect of cinnamon relevant to T2D......Page 534
Toxicological profile......Page 535
Overview of pharmacokinetics profile......Page 536
General summary and conclusions......Page 537
References......Page 539
Further reading......Page 547
16
The chemical and pharmacological basis of cloves (Syzygium aromaticum (L.) Merr. M.Perry) as potent......Page 548
Botanical and taxonomic perspectives......Page 549
Culinary and medicinal uses of clove......Page 552
Essential oils......Page 553
Flavonoids......Page 555
Phenolic acids and derivatives......Page 556
Tannins......Page 557
Terpenoids......Page 558
Antidiabetic effects-Crude extract and preparations......Page 562
Antidiabetic effects-Active principles of cloves......Page 564
Antiobesity and antihyperlipidaemic effects......Page 568
General summary and conclusion......Page 569
References......Page 571
Further reading......Page 575
17
The chemical and pharmacological basis of fenugreek (Trigonella foenum-graecum L.) as potential therapy for t .........Page 576
Botanical and taxonomic perspectives......Page 577
Uses as food and medicine......Page 580
The chemistry of fenugreek......Page 581
Oil components of fenugreek seeds......Page 582
Saponins......Page 584
Alkaloids......Page 590
Flavonoids......Page 592
Other shikimic acid-derived compounds of fenugreek seeds......Page 595
Carbohydrates and gums......Page 597
Unusual amino acid: 4-Hydroxyisoleucine......Page 599
Glycaemic control in various animal and in vitro models......Page 601
Hypolipidaemic and antiobesity effects in various animal and in vitro models......Page 603
Antihyperglycaemic effects......Page 606
Antihyperlipidaemic effects......Page 607
4-Hydroxyisoleucine......Page 608
Saponins......Page 611
Dietary fibre and carbohydrate fractions......Page 613
Fenugreek in other diabetes-related pathologies......Page 616
Antioxidant and organoprotective effects of fenugreek......Page 617
Anti-inflammatory effects......Page 620
Adverse effect......Page 622
Conclusions......Page 623
References......Page 624
Further reading......Page 633
18
The chemical and pharmacological basis of ginger (Zingiber officinale Roscoe) as potential therapy for diabet .........Page 635
Taxonomic and botanical perspectives......Page 636
Utilization of ginger as food and medicine......Page 639
Less-volatile components......Page 642
Essential oils......Page 645
Quality control measures......Page 646
Evidence of efficacy from animal experiments......Page 647
Evidence of efficacy from human studies......Page 648
Mechanisms of improvement of insulin signalling and glucose homeostasis by ginger products......Page 649
Evidence of efficacy from animal studies......Page 651
Mechanisms of antiobesity and antihyperlipidaemic effect of ginger......Page 652
Atherosclerosis......Page 655
Crude extract preparations......Page 656
Effects of the isolated compounds......Page 657
Platelet function......Page 660
Antioxidant effects as mechanisms for the diverse effects of ginger in diabetes and associated diseases......Page 661
Anti-inflammatory mechanisms......Page 663
Ginger in diabetic retinopathy......Page 667
Ginger in diabetic nephropathy......Page 668
Overview of pharmacokinetics profile......Page 669
Conclusions......Page 671
References......Page 672
Further readings......Page 682
19
The chemical and pharmacological basis of garlic (Allium sativum L.) as potential therapy for type 2 diabetes .........Page 684
Taxonomy and origin......Page 685
Garlic utilization as food and medicine......Page 686
Organosulphur compounds in fresh garlic preparations......Page 693
Aged garlic preparations......Page 695
Aged black garlic......Page 697
Phenolic composition of garlic......Page 698
Chemical variability of garlic products......Page 701
Evidence of efficacy from animal experiments......Page 702
Evidence of efficacy from human studies......Page 705
Evidence of efficacy from animal studies......Page 706
Evidence of efficacy from human studies......Page 707
Evidence of efficacy from animal studies......Page 708
Evidence of efficacy from human studies......Page 710
Improvement of insulin signalling and glucose homeostasis by garlic products......Page 711
Lipid lowering, antiobesity and anti-adipogenic effects of garlic......Page 712
Mechanisms of cardiovascular protection by garlic......Page 716
Mechanisms related to hydrogen sulphide (H2S)......Page 717
Mechanisms related to angiotensin converting enzyme (ACE)......Page 719
Mechanisms related to nitric oxide and other signalling pathways......Page 720
Mechanisms related to platelet function......Page 722
Antioxidant effects as mechanisms for the diverse effect of garlic in diabetes and associated diseases......Page 723
Anti-inflammatory mechanisms......Page 726
Garlic in diabetic nephropathy......Page 727
Overview of pharmacokinetics profile......Page 728
Toxicity remarks......Page 729
References......Page 730
Further reading......Page 743
20
The chemical and pharmacological basis of turmeric (Curcuma longa L.) as potential therapy for type 2 diabete .........Page 745
The chemistry of turmeric......Page 746
Antidiabetic effects in animal models......Page 752
Antidiabetic effects in human subjects......Page 753
Effects on animal models......Page 754
Effects on human subjects......Page 755
Neuropathy......Page 756
Endothelial dysfunction......Page 757
Nephropathy......Page 758
Retinopathy......Page 759
Wound healing......Page 761
Insulin signalling and glucose homeostasis......Page 762
Lipid lowering and anti-adipogenic effects......Page 764
Antioxidant mechanisms......Page 767
Anti-inflammatory mechanisms......Page 769
β-Cell protection......Page 771
Toxicology and pharmacokinetic profile......Page 772
General summary and conclusions......Page 773
References......Page 775
Further reading......Page 782
Section F: Potential modulators of type 2 diabetes and associated diseases: Beverages, other foods, and herbal supplements
......Page 784
21
Chemical and pharmacological evidences for coffee as a modulator of type 2 diabetes and metabolic syndrome......Page 785
Introduction......Page 786
Economic significance......Page 788
Taxonomy and botany......Page 792
The chemistry of coffee relevant to potential effect on metabolic syndrome......Page 795
The inverse association between coffee drinking and risk for T2D-Epidemiological evidences......Page 798
General antidiabetic effect......Page 801
Caffeine as an adenosine receptor antagonist......Page 803
Caffeine as a phosphodiesterase inhibitor......Page 805
Coffee as a modulator of glycaemic control and insulin sensitivity......Page 806
Antiobesity and lipid lowering verses hyperlipidaemic effects of coffee......Page 811
Antioxidant and anti-inflammatory mechanisms of coffee......Page 814
Coffee and hypertension......Page 817
Comments on bioavailability and toxicity......Page 818
Conclusions......Page 819
References......Page 820
Further reading......Page 830
22
The chemical and pharmacological basis of tea (Camellia sinensis (L.) Kuntze) as potential therapy for type 2 .........Page 831
The global tea industry......Page 832
Botany and taxonomy......Page 835
Chemistry......Page 838
General antidiabetic, antiobesity and lipid lowering effects in experimental animals......Page 843
General antioxidant effects......Page 859
Anti-inflammatory effects......Page 861
Effects on carbohydrate digestion and glucose absorption in the gut......Page 863
Effects on lipid digestion and faecal fat excretion......Page 864
Effects on insulin signalling and molecular targets in glycaemic control and fat metabolism......Page 865
Effects on endothelial dysfunction and cardiovascular system......Page 871
Overview of pharmacokinetics......Page 872
Epidemiology related to tea and T2D risks......Page 873
Inverse correlation between tea intake and cardiovascular risks in humans......Page 874
Glycaemic control in human subject......Page 876
Antiobesity and lipid lowering effect in human subjects......Page 877
Antihypertensive effect in human subjects......Page 882
Antioxidant effect of tea in human subjects......Page 883
Toxicity considerations......Page 884
References......Page 885
Further reading......Page 898
23
The chemical and pharmacological basis of rooibos (Aspalathus linearis (Burm. F.) R. Dahlgren) as potential t .........Page 899
Introduction......Page 900
Chemical components relevant to the pharmacology of rooibos......Page 903
The pharmacological basis of rooibos for diabetes and metabolic syndrome: In vitro and in vivo evidence......Page 909
Antioxidant activity......Page 916
Anti-inflammatory mechanisms......Page 917
Glucose and lipid metabolism......Page 919
Pancreatic β-cell protection and insulin release......Page 921
Antiobesity and anti-adipogenesis effects and lipid lowering effects......Page 922
Cardiovascular effect......Page 923
Overview of bioavailability and pharmacokinetics profile of rooibos......Page 926
References......Page 927
Further reading......Page 933
24
The chemical and pharmacological basis of yerba maté (Ilex paraguariensis A.St.-Hil.) as potential therapy......Page 934
Introduction......Page 935
Botanical and taxonomic perspectives......Page 936
Polyphenols......Page 937
Triterpenes and/or saponins......Page 943
Alkaloids......Page 945
Perspectives on variability of active components in mate extracts......Page 946
Evidences of efficacy of yerba mate for metabolic syndrome......Page 947
General antioxidant effects and mechanisms......Page 951
Anti-inflammatory mechanism......Page 953
Antihyperglycaemic and other effects on glucose homeostasis......Page 954
Antiobesity effect......Page 956
Pancreatic lipase and choleretic effects as antiobesity and lipid lowering mechanisms......Page 961
Cardiovascular effects......Page 962
Clinical trials and toxicological perspectives......Page 963
Conclusions......Page 966
References......Page 967
Further reading......Page 974
25
Other common and exotic foods with growing importance as antidiabetic agents......Page 975
Introduction......Page 976
The chemistry of cocoa active principles......Page 977
Antidiabetic and antiobesity effects of cocoa......Page 979
Human studies......Page 982
Introduction......Page 983
The chemistry of coconut......Page 984
Therapeutic potential of coconut for diabetes and associated diseases......Page 985
Introduction......Page 988
General antidiabetic effect of F. carica L. fruits......Page 989
Chemical components of F. carica fruits......Page 990
Antidiabetic effects of the active components......Page 992
Introduction......Page 993
M. oleifera as antidiabetic agent......Page 994
The active pharmacological components of M. oleifera and M. stenopetala......Page 997
Introduction......Page 1001
Soybean chemistry......Page 1002
Antidiabetic and related pharmacology in experimental models......Page 1003
Antidiabetic and related effects in human subjects......Page 1005
Introduction to sweet potato......Page 1006
Phytochemical components of sweet potato......Page 1008
Effects of sweet potato on diabetes and associated diseases......Page 1012
Introduction to walnuts......Page 1014
The chemistry and pharmacology of walnut (Juglans regia L.) seeds related to diabetes and associated diseases......Page 1015
The chemistry and pharmacology of walnut (Juglans regia L.) leaves related to diabetes and associated diseases......Page 1020
References......Page 1022
Further reading......Page 1037
26
Antidiabetic herbal medicines rebranded as dietary supplements......Page 1038
Overview of herbal medicines rebranding as supplements......Page 1039
Aloe vera as antidiabetic agent......Page 1041
Andrographis paniculata (Burm. F.) Wall. Ex Nees as antidiabetic agent......Page 1044
Experimental evidences for Banaba as antidiabetic agent......Page 1047
Overview of the genus and chemical profiles......Page 1053
Cassia auriculata-Now reclassified as Senna auriculata (L.) Roxb......Page 1054
Other Senna and Cassia species of interest......Page 1057
Ginkgo biloba L.......Page 1058
Overview of the genus Panax......Page 1064
Chemical composition of ginseng......Page 1065
Antidiabetic and antiobesity effects......Page 1068
Cardioprotective effects of ginsenosides......Page 1070
Perspectives from human studies on ginseng......Page 1071
The active pharmacological principles......Page 1072
General antidiabetic, antiobesity, and lipid lowering effects......Page 1075
Effects on the cardiovascular system......Page 1077
Perspectives from human studies......Page 1078
Overview of the plant......Page 1079
Potential active principles......Page 1080
General antidiabetic, antiobesity, and lipid lowering effects......Page 1084
Comparative assessments and mechanism of action for the active principles......Page 1085
Human study......Page 1087
Significance of olive leaves as food and medicine......Page 1088
Chemistry of the potential active principles......Page 1089
Antidiabetic effects of olive leaves......Page 1091
The pharmacology of olive leaf active principles related to diabetes and associated diseases......Page 1092
Effect of olive leaf extract on human subjects......Page 1093
Significance of Scutellaria baicalensis Georgi......Page 1094
Chemistry of Scutellaria baicalensis Georgi......Page 1095
Effects related to diabetes and/or metabolic syndrome......Page 1096
Significance of St John's wort-Hypericum perforatum L.......Page 1098
Standardized extracts and active principles......Page 1100
Potential therapy for diabetes and associated diseases......Page 1101
References......Page 1103
Further reading......Page 1122
A......Page 1124
B......Page 1127
C......Page 1128
D......Page 1130
E......Page 1131
F......Page 1132
G......Page 1133
H......Page 1136
I......Page 1137
L......Page 1138
M......Page 1139
O......Page 1140
P......Page 1141
R......Page 1143
S......Page 1144
T......Page 1145
W......Page 1147
Z......Page 1148
Back Cover......Page 1149