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DPP-IV, An Important Target for Antidiabetic Functional Food Design

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Abstract

Type 2 diabetes mellitus is a chronic metabolic disease that is characterized by hyperglycemia, which results from the body’s ineffective use of insulin (a gradual decline in insulin sensitivity and/or insulin secretion). It has been reported that between 347 and 371 million people worldwide currently have diabetes and that approximately 90 % have type 2 diabetes mellitus. It is forecasted that the number of diabetes deaths will double between 2005 and 2030, which will make diabetes the seventh leading cause of death in 2030.

In the USA, there are now ten different drug classes available to manage hyperglycemia in type 2 diabetic patients. However, not all of the drugs show the same level of safety (particularly cardiovascular safety). One of the most recent treatments for type 2 diabetes mellitus is the use of dipeptidyl peptidase-IV (DPP-IV) inhibitors. In addition to regulating postprandial glycemia, these drugs improve several cardiovascular risk factors. Thus, DPP-IV is a very interesting target for finding natural compounds that inhibit it and that can be used as bioactive compounds in functional food that prevents the development of type 2 diabetes mellitus.

This chapter (a) focuses on the importance of DPP-IV inhibition for type 2 diabetes prevention and treatment, (b) summarizes which natural products are known to inhibit DPP-IV, and (c) suggests how to use drug-discovery tools to improve the search for new DPP-IV inhibitors of natural origin.

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References

  1. International Diabetes Federation (2013) IDF Diabetes Atlas, 6th edn. Brussels, Belgium: International Diabetes Federation, http://www.idf.org/diabetesatlas

    Google Scholar 

  2. Daousi C, Casson IF, Gill GV, MacFarlane IA, Wilding JPH, Pinkney JH (2006) Prevalence of obesity in type 2 diabetes in secondary care: association with cardiovascular risk factors. Postgrad Med J 82:280–284

    CAS  Google Scholar 

  3. UK Prospective Diabetes Study (UKPDS) Group (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352:837–853

    Google Scholar 

  4. Kahn SE, Haffner SM, Heise MA et al (2006) Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 355:2427–2443

    CAS  Google Scholar 

  5. Ross SA, Dzida G, Vora J, Khunti K, Kaiser M, Ligthelm RJ (2011) Impact of weight gain on outcomes in type 2 diabetes. Curr Med Res Opin 27:1431–1438

    Google Scholar 

  6. Jacobson AM (2004) Impact of improved glycemic control on quality of life in patients with diabetes. Endocr Pract 10:502–508

    Google Scholar 

  7. International Diabetes Federation. IDF diabetes atlas. http://www.idf.org/diabetesatlas. Accessed 15 Aug 2013

  8. World Health Organization. Diabetes programme. http://www.who.int/diabetes/en/. Accessed 15 Aug 2013

  9. Morrish NJ, Wang SL, Stevens LK, Fuller JH, Keen H (2001) Mortality and causes of death in the WHO multinational study of vascular disease in diabetes. Diabetologia 44(Suppl 2):S14–S21

    Google Scholar 

  10. World Health Organization (2011). Global status report on noncommunicable diseases 2010. http://www.who.int/nmh/publications/ncd_report2010/en/. Accessed 15 Aug 2013

  11. Roglic G, Unwin N, Bennett PH, Mathers C, Tuomilehto J, Nag S, Connolly V, King H (2005) The burden of mortality attributable to diabetes: realistic estimates for the year 2000. Diabetes Care 28:2130–2135

    Google Scholar 

  12. World Health Organization (2011). Prevention of blindness and visual impairment. Action plan for the prevention of avoidable blindness. Global data on visual impairment 2010. http://www.who.int/entity/blindness/GLOBALDATAFINALforweb.pdf. Accessed 15 Aug 2013

  13. Guthrie RM (2012) Evolving therapeutic options for type 2 diabetes mellitus: an overview. Postgrad Med 124:82–89

    Google Scholar 

  14. US Food and Drug Administration (2008). Guidance for industry. Diabetes mellitus—evaluating cardiovascular risk in new anti-diabetic therapies to treat type 2 diabetes. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid-ances/ucm071627.pdf. Accessed 15 Aug 2013

  15. Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B (2009) Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 32:193–203

    CAS  Google Scholar 

  16. Hopsu-Havu VK, Sarimo SR (1967) Purification and characterization of an aminopeptidase hydrolyzing glycyl-proline-naphthylamide. Hoppe Seylers Z Physiol Chem 348:1540–1550

    CAS  Google Scholar 

  17. Rawlings ND, Tolle DP, Barrett AJ (2004) MEROPS: the peptidase database. Nucleic Acids Res 32:D160–D164

    CAS  Google Scholar 

  18. Power O, Nongonierma AB, Jakeman P, Fitzgerald RJ (2013) Food protein hydrolysates as a source of dipeptidyl peptidase IV inhibitory peptides for the management of type 2 diabetes. Proc Nutr Soc 73:34–46

    Google Scholar 

  19. Mendieta L, Tarrago T, Giralt E (2011) Recent patents of dipeptidyl peptidase IV inhibitors. Expert Opin Ther Pat 21:1693–1741

    CAS  Google Scholar 

  20. Gorrell MD (2005) Dipeptidyl peptidase IV and related enzymes in cell biology and liver disorders. Clin Sci (Lond) 108:277–292

    CAS  Google Scholar 

  21. Juillerat-Jeanneret L (2014) Dipeptidyl peptidase IV and its inhibitors: therapeutics for type 2 diabetes and what else? J Med Chem 57:2197–2212

    CAS  Google Scholar 

  22. Mentlein R (1999) Dipeptidyl-peptidase IV (CD26)–role in the inactivation of regulatory peptides. Regul Pept 85:9–24

    CAS  Google Scholar 

  23. Nabeno M, Akahoshi F, Kishida H, Miyaguchi I, Tanaka Y, Ishii S, Kadowaki T (2013) A comparative study of the binding modes of recently launched dipeptidyl peptidase IV inhibitors in the active site. Biochem Biophys Res Commun 434:191–196

    CAS  Google Scholar 

  24. Thoma R, Löffler B, Stihle M, Huber W, Ruf A, Hennig M (2003) Structural basis of proline-specific exopeptidase activity as observed in human dipeptidyl peptidase-IV. Structure 11:947–959

    CAS  Google Scholar 

  25. Doherty AM, Bock MG, Desai MC, Overington J, Plattner JJ, Stamford A, Wustrow D, Young H, Gwaltney SL, Stafford JA (2005) Inhibitors of dipeptidyl peptidase 4. Annu Rep Med Chem 40:149–165

    Google Scholar 

  26. Chien C-H, Huang L-H, Chou C-Y, Chen Y-S, Han Y-S, Chang G-G, Liang P-H, Chen X (2004) One site mutation disrupts dimer formation in human DPP-IV proteins. J Biol Chem 279:52338–52345

    CAS  Google Scholar 

  27. Engel M, Hoffmann T, Wagner L, Wermann M, Heiser U, Kiefersauer R, Huber R, Bode W, Demuth H-U, Brandstetter H (2003) The crystal structure of dipeptidyl peptidase IV (CD26) reveals its functional regulation and enzymatic mechanism. Proc Natl Acad Sci U S A 100:5063–5068

    CAS  Google Scholar 

  28. Pederson RA, White HA, Schlenzig D, Pauly RP, McIntosh CH, Demuth HU (1998) Improved glucose tolerance in Zucker fatty rats by oral administration of the dipeptidyl peptidase IV inhibitor isoleucine thiazolidide. Diabetes 47:1253–1258

    CAS  Google Scholar 

  29. Pospisilik JA, Stafford SG, Demuth H-U, McIntosh CHS, Pederson RA (2002) Long-term treatment with dipeptidyl peptidase IV inhibitor improves hepatic and peripheral insulin sensitivity in the VDF Zucker rat: a euglycemic-hyperinsulinemic clamp study. Diabetes 51:2677–2683

    CAS  Google Scholar 

  30. Cheng JD, Dunbrack RL, Valianou M, Rogatko A, Alpaugh RK, Weiner LM (2002) Promotion of tumor growth by murine fibroblast activation protein, a serine protease, in an animal model. Cancer Res 62:4767–4772

    CAS  Google Scholar 

  31. Kajiyama H, Kikkawa F, Suzuki T, Shibata K, Ino K, Mizutani S (2002) Prolonged survival and decreased invasive activity attributable to dipeptidyl peptidase IV overexpression in ovarian carcinoma. Cancer Res 62:2753–2757

    CAS  Google Scholar 

  32. Ho L, Aytac U, Stephens LC et al (2001) In vitro and in vivo antitumor effect of the anti-CD26 monoclonal antibody 1F7 on human CD30+ anaplastic large cell T-cell lymphoma Karpas 299. Clin Cancer Res 7:2031–2040

    CAS  Google Scholar 

  33. Ussher JR, Sutendra G, Jaswal JS (2012) The impact of current and novel anti-diabetic therapies on cardiovascular risk. Future Cardiol 8:895–912

    CAS  Google Scholar 

  34. Zhong J, Rao X, Rajagopalan S (2013) An emerging role of dipeptidyl peptidase 4 (DPP4) beyond glucose control: potential implications in cardiovascular disease. Atherosclerosis 226:305–314

    CAS  Google Scholar 

  35. Patil HR, Al Badarin FJ, Al Shami HA, Bhatti SK, Lavie CJ, Bell DSH, O’Keefe JH (2012) Meta-analysis of effect of dipeptidyl peptidase-4 inhibitors on cardiovascular risk in type 2 diabetes mellitus. Am J Cardiol 110:826–833

    CAS  Google Scholar 

  36. Frederich R, Alexander JH, Fiedorek FT, Donovan M, Berglind N, Harris S, Chen R, Wolf R, Mahaffey KW (2010) A systematic assessment of cardiovascular outcomes in the saxagliptin drug development program for type 2 diabetes. Postgrad Med 122:16–27

    Google Scholar 

  37. Scheen AJ (2013) Cardiovascular effects of gliptins. Nat Rev Cardiol 10:73–84

    CAS  Google Scholar 

  38. Simsek S, de Galan BE (2012) Cardiovascular protective properties of incretin-based therapies in type 2 diabetes. Curr Opin Lipidol 23:540–547

    CAS  Google Scholar 

  39. Dai Y, Dai D, Mercanti F, Ding Z, Wang X, Mehta JL (2013) Dipeptidyl peptidase-4 inhibitors in cardioprotection: a promising therapeutic approach. Acta Diabetol 50:827–835

    CAS  Google Scholar 

  40. Scheen AJ (2013) Cardiovascular effects of dipeptidyl peptidase-4 inhibitors: from risk factors to clinical outcomes. Postgrad Med 125:7–20

    Google Scholar 

  41. Yousefzadeh P, Wang X (2013) The effects of dipeptidyl peptidase-4 inhibitors on cardiovascular disease risks in type 2 diabetes mellitus. J Diabetes Res 2013:459821

    Google Scholar 

  42. Balakumar P, Dhanaraj SA (2013) Cardiovascular pleiotropic actions of DPP-4 inhibitors: a step at the cutting edge in understanding their additional therapeutic potentials. Cell Signal 25:1799–1803

    CAS  Google Scholar 

  43. Wang XM, Yao T-W, Nadvi NA, Osborne B, McCaughan GW, Gorrell MD (2008) Fibroblast activation protein and chronic liver disease. Front Biosci 13:3168–3180

    CAS  Google Scholar 

  44. Kirby M, Yu DMT, O’Connor S, Gorrell MD (2010) Inhibitor selectivity in the clinical application of dipeptidyl peptidase-4 inhibition. Clin Sci (Lond) 118:31–41

    CAS  Google Scholar 

  45. Lankas GR, Leiting B, Roy RS et al (2005) Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: potential importance of selectivity over dipeptidyl peptidases 8 and 9. Diabetes 54:2988–2994

    CAS  Google Scholar 

  46. Deacon CF, Ahrén B (2011) Physiology of incretins in health and disease. Rev Diabet Stud 8:293–306

    Google Scholar 

  47. Tortosa F, Dotta F (2013) Incretin hormones and beta-cell mass expansion: what we know and what is missing? Arch Physiol Biochem 119:161–169

    CAS  Google Scholar 

  48. Ahrén B (2013) Incretin dysfunction in type 2 diabetes: clinical impact and future perspectives. Diabetes Metab 39:195–201

    Google Scholar 

  49. Opinto G, Natalicchio A, Marchetti P (2013) Physiology of incretins and loss of incretin effect in type 2 diabetes and obesity. Arch Physiol Biochem 119:170–178

    CAS  Google Scholar 

  50. Brunton S (2013) Integrating incretin-based therapy into type 2 diabetes management. Vital Signs 62:S1–S8

    Google Scholar 

  51. Papamargaritis D, Miras AD, le Roux CW (2013) Influence of diabetes surgery on gut hormones and incretins. Nutr Hosp 28(Suppl 2):95–103

    CAS  Google Scholar 

  52. Meier JJ, Nauck MA, Schmidt WE, Gallwitz B (2002) Gastric inhibitory polypeptide: the neglected incretin revisited. Regul Pept 107:1–13

    CAS  Google Scholar 

  53. Green BD, Flatt PR, Bailey CJ (2006) Inhibition of dipeptidylpeptidase IV activity as a therapy of type 2 diabetes. Expert Opin Emerg Drugs 11:525–539

    CAS  Google Scholar 

  54. Lindgren O, Mari A, Deacon CF, Carr RD, Winzell MS, Vikman J, Ahrén B (2009) Differential islet and incretin hormone responses in morning versus afternoon after standardized meal in healthy men. J Clin Endocrinol Metab 94:2887–2892

    CAS  Google Scholar 

  55. Ahrén B, Carr RD, Deacon CF (2010) Incretin hormone secretion over the day. Vitam Horm 84:203–220

    Google Scholar 

  56. Zettl H, Schubert-Zsilavecz M, Steinhilber D (2010) Medicinal chemistry of incretin mimetics and DPP-4 inhibitors. ChemMedChem 5:179–185

    CAS  Google Scholar 

  57. Drucker DJ, Nauck MA (2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368:1696–1705

    CAS  Google Scholar 

  58. Holst JJ, Vilsbøll T, Deacon CF (2009) The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol 297:127–136

    CAS  Google Scholar 

  59. Holst JJ, Deacon CF (2004) Glucagon-like peptide 1 and inhibitors of dipeptidyl peptidase IV in the treatment of type 2 diabetes mellitus. Curr Opin Pharmacol 4:589–596

    CAS  Google Scholar 

  60. Baggio LL, Drucker DJ (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132:2131–2157

    CAS  Google Scholar 

  61. Drucker DJ (2003) Therapeutic potential of dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes. Expert Opin Investig Drugs 12:87–100

    CAS  Google Scholar 

  62. Højberg PV, Vilsbøll T, Rabøl R, Knop FK, Bache M, Krarup T, Holst JJ, Madsbad S (2009) Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. Diabetologia 52:199–207

    Google Scholar 

  63. Hansen KB, Vilsbøll T, Bagger JI, Holst JJ, Knop FK (2012) Impaired incretin-induced amplification of insulin secretion after glucose homeostatic dysregulation in healthy subjects. J Clin Endocrinol Metab 97:1363–1370

    CAS  Google Scholar 

  64. Demuth H-U, McIntosh CHS, Pederson RA (2005) Type 2 diabetes–therapy with dipeptidyl peptidase IV inhibitors. Biochim Biophys Acta 1751:33–44

    CAS  Google Scholar 

  65. Kim S-H, Lee S-H, Yim H-J (2013) Gemigliptin, a novel dipeptidyl peptidase 4 inhibitor: first new anti-diabetic drug in the history of Korean pharmaceutical industry. Arch Pharm Res 36:1185–1188

    CAS  Google Scholar 

  66. US National Library of Medicine. National Institutes of Health. MedlinePlus (2014). Sitagliptin. http://www.nlm.nih.gov/medlineplus/druginfo/meds/a606023.html. Accessed 21 Nov 2013

  67. US National Library of Medicine. National Institutes of Health. MedlinePlus (2014). Saxagliptin. http://www.nlm.nih.gov/medlineplus/druginfo/meds/a610003.html. Accessed 21 Nov 2013

  68. US National Library of Medicine. National Institutes of Health. MedlinePlus (2014). Linagliptin. http://www.nlm.nih.gov/medlineplus/druginfo/meds/a611036.html. Accessed 21 Nov 2013

  69. Noel RA, Braun DK, Patterson RE, Bloomgren GL (2009) Increased risk of acute pancreatitis and biliary disease observed in patients with type 2 diabetes: a retrospective cohort study. Diabetes Care 32:834–838

    Google Scholar 

  70. Engel SS, Williams-Herman DE, Golm GT, Clay RJ, Machotka S V, Kaufman KD, Goldstein BJ (2010) Sitagliptin: review of preclinical and clinical data regarding incidence of pancreatitis. Int J Clin Pract 64:984–990

    CAS  Google Scholar 

  71. Williams-Herman D, Engel SS, Round E, Johnson J, Golm GT, Guo H, Musser BJ, Davies MJ, Kaufman KD, Goldstein BJ (2010) Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes. BMC Endocr Disord 10:7

    Google Scholar 

  72. Engel SS, Round E, Golm GT, Kaufman KD, Goldstein BJ (2013) Safety and tolerability of sitagliptin in type 2 diabetes: pooled analysis of 25 clinical studies. Diabetes Ther 4:119–145

    Google Scholar 

  73. Monami M, Dicembrini I, Mannucci E (2014) Dipeptidyl peptidase-4 inhibitors and pancreatitis risk: a meta-analysis of randomized clinical trials. Diabetes Obes Metab 16:48–56

    CAS  Google Scholar 

  74. Scheen A (2013) Gliptins (dipeptidyl peptidase-4 inhibitors) and risk of acute pancreatitis. Expert Opin Drug Saf 12:545–557

    CAS  Google Scholar 

  75. Deacon CF, Holst JJ (2013) Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes: comparison, efficacy and safety. Expert Opin Pharmacother 14:2047–2058

    CAS  Google Scholar 

  76. Zanchi A, Lehmann R, Philippe J (2012) Anti-diabetic drugs and kidney disease–recommendations of the Swiss Society for Endocrinology and Diabetology. Swiss Med Wkly 142:w13629

    Google Scholar 

  77. Ramirez G, Morrison AD, Bittle PA (2013) Clinical practice considerations and review of the literature for the use of DPP-4 inhibitors in patients with type 2 diabetes and chronic kidney disease. Endocr Pract 19:1025–1034

    Google Scholar 

  78. Kuhn B, Hennig M, Mattei P (2007) Molecular recognition of ligands in dipeptidyl peptidase IV. Curr Top Med Chem 7:609–619

    CAS  Google Scholar 

  79. Engel M, Hoffmann T, Manhart S, Heiser U, Chambre S, Huber R, Demuth H-U, Bode W (2006) Rigidity and flexibility of dipeptidyl peptidase IV: crystal structures of and docking experiments with DPIV. J Mol Biol 355:768–783

    CAS  Google Scholar 

  80. Li C, Shen J, Li W, Lu C (2011) Possible ligand release pathway of dipeptidyl peptidase IV investigated by molecular dynamics simulations. Proteins Struct Funct Bioinforma 79:1800–1809

    CAS  Google Scholar 

  81. Schechter I, Berger A (2012) On the size of the active site in proteases. I. Papain. 1967. Biochem Biophys Res Commun 425:497–502

    CAS  Google Scholar 

  82. Weber AE (2004) Dipeptidyl peptidase IV inhibitors for the treatment of diabetes. J Med Chem 47:4135–4141

    CAS  Google Scholar 

  83. Wallace MB, Feng J, Zhang Z, Skene RJ, Shi L, Caster CL, Kassel DB, Xu R, Gwaltney SL (2008) Structure-based design and synthesis of benzimidazole derivatives as dipeptidyl peptidase IV inhibitors. Bioorg Med Chem Lett 18:2362–2367

    CAS  Google Scholar 

  84. Patel B, Ghate M (2013) Computational studies on structurally diverse dipeptidyl peptidase IV inhibitors: an approach for new anti-diabetic drug development. Med Chem Res 22:4505–4521

    CAS  Google Scholar 

  85. Al-Masri IM, Mohammad MK, Taha MO (2008) Discovery of DPP IV inhibitors by pharmacophore modeling and QSAR analysis followed by in silico screening. ChemMedChem 3:1763–1779

    CAS  Google Scholar 

  86. Aertgeerts K, Ye S, Tennant MG, Kraus ML, Rogers J, Sang B-C, Skene RJ, Webb DR, Prasad GS (2004) Crystal structure of human dipeptidyl peptidase IV in complex with a decapeptide reveals details on substrate specificity and tetrahedral intermediate formation. Protein Sci 13:412–421

    CAS  Google Scholar 

  87. Bjelke JR, Christensen J, Branner S, Wagtmann N, Olsen C, Kanstrup AB, Rasmussen HB (2004) Tyrosine 547 constitutes an essential part of the catalytic mechanism of dipeptidyl peptidase IV. J Biol Chem 279:34691–34697

    CAS  Google Scholar 

  88. Yoshida T, Akahoshi F, Sakashita H, et al (2012) Discovery and preclinical profile of teneligliptin (3-[(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl]thiazolidine): a highly potent, selective, long-lasting and orally active dipeptidyl peptidase IV inhibitor for t. Bioorg Med Chem 20:5705–5719

    CAS  Google Scholar 

  89. Yoshida T, Akahoshi F, Sakashita H, Sonda S, Takeuchi M, Tanaka Y, Nabeno M, Kishida H, Miyaguchi I, Hayashi Y (2012) Fused bicyclic heteroarylpiperazine-substituted L-prolylthiazolidines as highly potent DPP-4 inhibitors lacking the electrophilic nitrile group. Bioorg Med Chem 20:5033–5041

    CAS  Google Scholar 

  90. Edmondson SD, Mastracchio A, Cox JM et al (2009) Aminopiperidine-fused imidazoles as dipeptidyl peptidase-IV inhibitors. Bioorg Med Chem Lett 19:4097–4101

    CAS  Google Scholar 

  91. Edmondson SD, Mastracchio A, Mathvink RJ et al (2006) (2S,3S)-3-Amino-4-(3,3-difluoropyrrolidin-1-yl)-N, N-dimethyl-4-oxo-2-(4-[1,2,4]triazolo[1,5-a]-pyridin-6-ylphenyl)butanamide: a selective alpha-amino amide dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem 49:3614–3627

    CAS  Google Scholar 

  92. Edmondson SD, Wei L, Xu J et al (2008) Fluoroolefins as amide bond mimics in dipeptidyl peptidase IV inhibitors. Bioorg Med Chem Lett 18:2409–2413

    CAS  Google Scholar 

  93. Biftu T, Scapin G, Singh S et al (2007) Rational design of a novel, potent, and orally bioavailable cyclohexylamine DPP-4 inhibitor by application of molecular modeling and X-ray crystallography of sitagliptin. Bioorg Med Chem Lett 17:3384–3387

    CAS  Google Scholar 

  94. Eckhardt M, Langkopf E, Mark M et al (2007) 8-(3-®-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. J Med Chem 50:6450–6453

    CAS  Google Scholar 

  95. Kaelin DE, Smenton AL, Eiermann GJ et al (2007) 4-arylcyclohexylalanine analogs as potent, selective, and orally active inhibitors of dipeptidyl peptidase IV. Bioorg Med Chem Lett 17:5806–5811

    CAS  Google Scholar 

  96. Nordhoff S, Cerezo-Gálvez S, Deppe H, Hill O, López-Canet M, Rummey C, Thiemann M, Matassa VG, Edwards PJ, Feurer A (2009) Discovery of beta-homophenylalanine based pyrrolidin-2-ylmethyl amides and sulfonamides as highly potent and selective inhibitors of dipeptidyl peptidase IV. Bioorg Med Chem Lett 19:4201–4203

    CAS  Google Scholar 

  97. Salam NK, Nuti R, Sherman W (2009) Novel method for generating structure-based pharmacophores using energetic analysis. J Chem Inf Model 49:2356–2368

    CAS  Google Scholar 

  98. Loving K, Salam NK, Sherman W (2009) Energetic analysis of fragment docking and application to structure-based pharmacophore hypothesis generation. J Comput Aided Mol Des 23:541–554

    CAS  Google Scholar 

  99. Guasch L, Ojeda MJ, González-Abuín N et al (2012) Identification of novel human dipeptidyl peptidase-IV inhibitors of natural origin (part I): virtual screening and activity assays. PLoS One 7:e44971

    CAS  Google Scholar 

  100. Rummey C, Metz G (2007) Homology models of dipeptidyl peptidases 8 and 9 with a focus on loop predictions near the active site. Proteins 66:160–171

    CAS  Google Scholar 

  101. Janardhan S, Reddy YP (2011) Homology modeling and molecular docking studies of human DPP8 and DPP9. Int J Pharma Res Dev 2:131–146

    Google Scholar 

  102. Pitman MR, Menz RI, Abbott CA (2006) Prediction of dipeptidyl peptidase (DP) 8 structure by homology modelling. Adv Exp Med Biol 575:33–42

    CAS  Google Scholar 

  103. Tanwar O, Deora GS, Tanwar L, Kumar G, Janardhan S, Alam MM, Shaquiquzzaman M, Akhter M (2014) Novel hydrazine derivatives as selective DPP-IV inhibitors: findings from virtual screening and validation through molecular dynamics simulations. J Mol Model 20:2118

    Google Scholar 

  104. Kang NS, Ahn JH, Kim SS, Chae CH, Yoo S-E (2007) Docking-based 3D-QSAR study for selectivity of DPP4, DPP8, and DPP9 inhibitors. Bioorg Med Chem Lett 17:3716–3721

    CAS  Google Scholar 

  105. Patel BD, Ghate MD (2014) Recent approaches to medicinal chemistry and therapeutic potential of dipeptidyl peptidase-4 (DPP-4) inhibitors. Eur J Med Chem 74:574–605

    CAS  Google Scholar 

  106. Ghate M, Jain SV (2013) Structure based lead optimization approach in discovery of selective DPP4 inhibitors. Mini Rev Med Chem 13:888–914

    CAS  Google Scholar 

  107. Fukuda-Tsuru S, Anabuki J, Abe Y, Yoshida K, Ishii S (2012) A novel, potent, and long-lasting dipeptidyl peptidase-4 inhibitor, teneligliptin, improves postprandial hyperglycemia and dyslipidemia after single and repeated administrations. Eur J Pharmacol 696:194–202

    CAS  Google Scholar 

  108. Ghate M, Jain S (2014) Fragment based HQSAR modeling and docking analysis of conformationally rigid 3-azabicyclo hexane derivatives to design selective DPP-4 inhibitors. Lett Drug Des Discov 11:184–198

    CAS  Google Scholar 

  109. American Diabetes Association (2014) Standards of medical care in diabetes–2014. Diabetes Care 37(Suppl 1):S14–S80

    Google Scholar 

  110. Rollinger JM, Stuppner H, Langer T (2008) Virtual screening for the discovery of bioactive natural products. Prog drug Res 65:211, 213–249

    Google Scholar 

  111. Schuster D, Wolber G (2010) Identification of bioactive natural products by pharmacophore-based virtual screening. Curr Pharm Des 16:1666–1681

    CAS  Google Scholar 

  112. Martinez-Mayorga K, Medina-Franco JL (2009) Chemoinformatics-applications in food chemistry. Adv Food Nutr Res 58:33–56

    CAS  Google Scholar 

  113. Ferguson LLR (2009) Nutrigenomics approaches to functional foods. J Am Diet Assoc 109:452–458

    CAS  Google Scholar 

  114. Pascual I, Lopéz A, Gómez H, Chappé M, Saroyán A, González Y, Cisneros M, Charli JL, Chávez MDLA (2007) Screening of inhibitors of porcine dipeptidyl peptidase IV activity in aqueous extracts from marine organisms. Enzyme Microb Technol 40:414–419

    CAS  Google Scholar 

  115. Al-masri IM, Mohammad MK, Tahaa MO (2009) Inhibition of dipeptidyl peptidase IV (DPP IV) is one of the mechanisms explaining the hypoglycemic effect of berberine. J Enzyme Inhib Med Chem 24:1061–1066

    CAS  Google Scholar 

  116. Hamden K, Bengara A, Amri Z, Elfeki A (2013) Experimental diabetes treated with trigonelline: effect on key enzymes related to diabetes and hypertension, β-cell and liver function. Mol Cell Biochem 381:85–94

    CAS  Google Scholar 

  117. Antonyan A, De A, Vitali L, Pettinari R, Marchetti F, Gigliobianco MR, Pettinari C, Camaioni E, Lupidi G (2014) Evaluation of (arene)Ru(II) complexes of curcumin as inhibitors of dipeptidyl peptidase IV. Biochimie 99:146–152

    CAS  Google Scholar 

  118. González-Abuín N, Martínez-Micaelo N, Blay M, Pujadas G, Garcia-Vallvé S, Pinent M, Ardévol A (2012) Grape seed-derived procyanidins decrease dipeptidyl-peptidase 4 activity and expression. J Agric Food Chem 60:9055–9061

    Google Scholar 

  119. Zhang S, Lu W, Liu X, Diao Y, Bai F, Wang L, Shan L, Huang J, Li H, Zhang W (2011) Fast and effective identification of the bioactive compounds and their targets from medicinal plants via computational chemical biology approach. MedChemComm 2:471

    CAS  Google Scholar 

  120. Guasch L, Sala E, Ojeda MJ, Valls C, Bladé C, Mulero M, Blay M, Ardévol A, Garcia-Vallvé S, Pujadas G (2012) Identification of novel human dipeptidyl peptidase-IV inhibitors of natural origin (part II): in silico prediction in anti-diabetic extracts. PLoS One 7:e44972

    CAS  Google Scholar 

  121. Fan J, Johnson MH, Lila MA, Yousef G, de Mejia EG (2013) Berry and citrus phenolic compounds inhibit dipeptidyl peptidase IV: implications in diabetes management. Evid Based Complement Alternat Med 2013:479505

    Google Scholar 

  122. Parmar HS, Jain P, Chauhan DS et al (2012) DPP-IV inhibitory potential of naringin: an in silico, in vitro and in vivo study. Diabetes Res Clin Pract 97:105–111

    CAS  Google Scholar 

  123. Geng Y, Lu Z-M, Huang W, Xu H-Y, Shi J-S, Xu Z-H (2013) Bioassay-guided isolation of DPP-4 inhibitory fractions from extracts of submerged cultured of Inonotus obliquus. Molecules 18:1150–1161

    CAS  Google Scholar 

  124. Bharti SK, Krishnan S, Kumar A, Rajak KK, Murari K, Bharti BK, Gupta AK (2012) Antihyperglycemic activity with DPP-IV inhibition of alkaloids from seed extract of Castanospermum australe: investigation by experimental validation and molecular docking. Phytomedicine 20:24–31

    CAS  Google Scholar 

  125. Bellé LP, Bitencourt PER, Abdalla FH, Bona KS de, Peres A, Maders LDK, Moretto MB (2013) Aqueous seed extract of Syzygium cumini inhibits the dipeptidyl peptidase IV and adenosine deaminase activities, but it does not change the CD26 expression in lymphocytes in vitro. J Physiol Biochem 69:119–124

    Google Scholar 

  126. Lacroix IME, Li-Chan ECY (2012) Evaluation of the potential of dietary proteins as precursors of dipeptidyl peptidase (DPP)-IV inhibitors by an in silico approach. J Funct Foods 4:403–422

    CAS  Google Scholar 

  127. Nongonierma AB, Fitzgerald RJ (2014) Susceptibility of milk protein-derived peptides to dipeptidyl peptidase IV (DPP-IV) hydrolysis. Food Chem 145:845–852

    CAS  Google Scholar 

  128. Rahfeld J, Schierhorn M, Hartrodt B, Neubert K, Heins J (1991) Are diprotin A (Ile-Pro-Ile) and diprotin B (Val-Pro-Leu) inhibitors or substrates of dipeptidyl peptidase IV? Biochim Biophys Acta 1076:314–316

    CAS  Google Scholar 

  129. Tulipano G, Sibilia V, Caroli AM, Cocchi D (2011) Whey proteins as source of dipeptidyl dipeptidase IV (dipeptidyl peptidase-4) inhibitors. Peptides 32:835–838

    CAS  Google Scholar 

  130. Nongonierma AB, FitzGerald RJ (2013) Dipeptidyl peptidase IV inhibitory and antioxidative properties of milk protein-derived dipeptides and hydrolysates. Peptides 39:157–163

    CAS  Google Scholar 

  131. Silveira ST, Martínez-Maqueda D, Recio I, Hernández-Ledesma B (2013) Dipeptidyl peptidase-IV inhibitory peptides generated by tryptic hydrolysis of a whey protein concentrate rich in β-lactoglobulin. Food Chem 141:1072–1077

    CAS  Google Scholar 

  132. Hatanaka T, Inoue Y, Arima J, Kumagai Y, Usuki H, Kawakami K, Kimura M, Mukaihara T (2012) Production of dipeptidyl peptidase IV inhibitory peptides from defatted rice bran. Food Chem 134:797–802

    CAS  Google Scholar 

  133. Huang S-L, Jao C-L, Ho K-P, Hsu K-C (2012) Dipeptidyl-peptidase IV inhibitory activity of peptides derived from tuna cooking juice hydrolysates. Peptides 35:114–121

    CAS  Google Scholar 

  134. Gallego M, Aristoy M-C, Toldrá F (2013) Dipeptidyl peptidase IV inhibitory peptides generated in Spanish dry-cured ham. Meat Sci 96:757–761

    Google Scholar 

  135. Lacroix IME, Li-Chan ECY (2012) Dipeptidyl peptidase-IV inhibitory activity of dairy protein hydrolysates. Int Dairy J 25:97–102

    CAS  Google Scholar 

  136. Velarde-Salcedo AJ, Barrera-Pacheco A, Lara-González S, Montero-Morán GM, Díaz-Gois A, González de Mejia E, Barba de la Rosa AP (2013) In vitro inhibition of dipeptidyl peptidase IV by peptides derived from the hydrolysis of amaranth (Amaranthus hypochondriacus L.) proteins. Food Chem 136:758–764

    CAS  Google Scholar 

  137. Nongonierma AB, Mooney C, Shields DC, Fitzgerald RJ (2013) Inhibition of dipeptidyl peptidase IV and xanthine oxidase by amino acids and dipeptides. Food Chem 141:644–653

    CAS  Google Scholar 

  138. Li-Chan ECY, Hunag S-L, Jao C-L, Ho K-P, Hsu K-C (2012) Peptides derived from atlantic salmon skin gelatin as dipeptidyl-peptidase IV inhibitors. J Agric Food Chem 60:973–978

    CAS  Google Scholar 

  139. Uenishi H, Kabuki T, Seto Y, Serizawa A, Nakajima H (2012) Isolation and identification of casein-derived dipeptidyl-peptidase 4 (DPP-4)-inhibitory peptide LPQNIPPL from gouda-type cheese and its effect on plasma glucose in rats. Int Dairy J 22:24–30

    CAS  Google Scholar 

  140. Uchida M, Ohshiba Y, Mogami O (2011) Novel dipeptidyl peptidase-4-inhibiting peptide derived from β-lactoglobulin. J Pharmacol Sci 117:63–66

    CAS  Google Scholar 

  141. Dziuba M, Dziuba B, Iwaniak A (2009) Milk proteins as precursors of bioactive peptides. Acta Sci Pol Technol Aliment 8(1):71–90 (http://www.food.actapol.net/volume8/issue1/abstract-7.html)

    CAS  Google Scholar 

  142. Minkiewicz P, Dziuba J, Michalska J (2011) Bovine meat proteins as potential precursors of biologically active peptides—a computational study based on the BIOPEP database. Food Sci Technol Int 17:39–45

    CAS  Google Scholar 

  143. Abe M, Akiyama T, Umezawa Y, Yamamoto K, Nagai M, Yamazaki H, Ichikawa Y-I, Muraoka Y (2005) Synthesis and biological activity of sulphostin analogues, novel dipeptidyl peptidase IV inhibitors. Bioorg Med Chem 13:785–797

    CAS  Google Scholar 

  144. Akiyama T, Abe M, Harada S et al (2001) Sulphostin, a potent inhibitor for dipeptidyl peptidase IV from Streptomyces sp. MK251–43F3. J Antibiot (Tokyo) 54:744–746

    CAS  Google Scholar 

  145. Umezawa H, Aoyagi T, Ogawa K, Naganawa H, Hamada M, Takeuchi T (1984) Diprotins A and B, inhibitors of dipeptidyl aminopeptidase IV, produced by bacteria. J Antibiot (Tokyo) 37:422–425

    CAS  Google Scholar 

  146. Trellet M, Melquiond A, Bonvin A (2013) A unified conformational selection and induced fit approach to protein-peptide docking. PLoS One 8:e58769

    CAS  Google Scholar 

  147. Albericio F, Kruger HG (2012) Therapeutic peptides. Future Med Chem 4:1527–1531

    CAS  Google Scholar 

  148. Yan TR, Ho SC, Hou CL (1992) Catalytic properties of X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis subsp. cremoris nTR. Biosci Biotechnol Biochem 56:704–707

    CAS  Google Scholar 

  149. Lorey S, Stöckel-Maschek A, Faust J et al (2003) Different modes of dipeptidyl peptidase IV (CD26) inhibition by oligopeptides derived from the N-terminus of HIV-1 Tat indicate at least two inhibitor binding sites. Eur J Biochem 270:2147–2156

    CAS  Google Scholar 

  150. Valli M, dos Santos RN, Figueira LD, Nakajima CH, Castro-Gamboa I, Andricopulo AD, Bolzani VS (2013) Development of a natural products database from the biodiversity of Brazil. J Nat Prod 76:439–444

    CAS  Google Scholar 

  151. Chen CY-C (2011) TCM database@Taiwan: the world’s largest traditional Chinese medicine database for drug screening in silico. PLoS One 6:e15939

    CAS  Google Scholar 

  152. Elsevier Reaxys chemistry workflow solution. http://www.reaxys.com. Accessed 20 Jan 2014

  153. Parasuraman S (2012) Protein data bank. J Pharmacol Pharmacother 3:351–352

    CAS  Google Scholar 

  154. Irwin JJ, Sterling T, Mysinger MM, Bolstad ES, Coleman RG (2012) ZINC: a free tool to discover chemistry for biology. J Chem Inf Model 52:1757–1768

    CAS  Google Scholar 

  155. Black OF, Kelly JW (1927) Pseudo ephedrine from Ephedra alata. Am J Pharm 99:748–751

    CAS  Google Scholar 

  156. Shabana MM, Mirhom YW, Genenah AA, Aboutabl EA, Amer HA (1990) Study into wild Egyptian plants of potential medicinal activity. Ninth communication: hypoglycaemic activity of some selected plants in normal fasting and alloxanised rats. Arch Exp Veterinarmed 44:389–394

    CAS  Google Scholar 

  157. Konno C, Mizuno T, Hikino H (1985) Isolation and hypoglycemic activity of ephedrans A, B, C, D and E, glycans of Ephedra distachya herbs. Planta Med 51:162–163

    Google Scholar 

  158. Grue-Sorensen G, Spenser ID (1989) The biosynthesis of ephedrine. Can J Chem 67:998–1009

    Google Scholar 

  159. Ito K, Haruna M, Furukawa H (1975) Studies on the erythrina alkaloids. X. Alkaloids of several Erythrina plants from Singapore (author’s transl). Yakugaku Zasshi 95:358–362

    CAS  Google Scholar 

  160. Kumar A, Lingadurai S, Shrivastava TP, Bhattacharya S, Haldar PK (2011) Hypoglycemic activity of Erythrina variegata leaf in streptozotocin-induced diabetic rats. Pharm Biol 49:577–582

    Google Scholar 

  161. Oh WK, Lee C-H, Seo JH, Chung MY, Cui L, Fomum ZT, Kang JS, Lee HS (2009) Diacylglycerol acyltransferase-inhibitory compounds from Erythrina senegalensis. Arch Pharm Res 32:43–47

    CAS  Google Scholar 

  162. Na M, Jang J, Njamen D, Mbafor JT, Fomum ZT, Kim BY, Oh WK, Ahn JS (2006) Protein tyrosine phosphatase-1B inhibitory activity of isoprenylated flavonoids isolated from Erythrina mildbraedii. J Nat Prod 69:1572–1576

    CAS  Google Scholar 

  163. Bae EY, Na M, Njamen D, Mbafor JT, Fomum ZT, Cui L, Choung DH, Kim BY, Oh WK, Ahn JS (2006) Inhibition of protein tyrosine phosphatase 1B by prenylated isoflavonoids isolated from the stem bark of Erythrina addisoniae. Planta Med 72:945–948

    CAS  Google Scholar 

  164. Benn MH, Shustov G, Shustova L, Majak W, Bai Y, Fairey NA (1996) Isolation and characterization of two guanidines from Galega orientalis Lam. Cv. Gale (fodder galega). J Agric Food Chem 44:2779–2781

    CAS  Google Scholar 

  165. Vuksan V, Sievenpiper JL (2005) Herbal remedies in the management of diabetes: lessons learned from the study of ginseng. Nutr Metab Cardiovasc Dis 15:149–160

    Google Scholar 

  166. Michel KH, Sandberg F, Haglid F, Norin T (1967) Alkaloids of Haloxylon salicornicum (Moq.-Tand.) Boiss. Acta Pharm Suec 4:97–116

    CAS  Google Scholar 

  167. Brack A (1962) Verlauf der Alkaloidbildung durch den Clavicepsstamm von Pennisetum typhoideum Rich. in saprophytischer Kultur. 54. Mitteilung über Mutterkornalkaloide. Arch Pharm (Weinheim) 295:510–515

    CAS  Google Scholar 

  168. Shukla K, Narain JP, Puri P, Gupta A, Bijlani RL, Mahapatra SC, Karmarkar MG (1991) Glycaemic response to maize, bajra and barley. Indian J Physiol Pharmacol 35:249–254

    CAS  Google Scholar 

  169. Sheludko Y, Gerasimenko I, Kolshorn H, Stöckigt J (2002) New alkaloids of the sarpagine group from Rauvolfia serpentina hairy root culture. J Nat Prod 65:1006–1010

    CAS  Google Scholar 

  170. Benzi G, Villa RF, Dossena M, Vercesi L, Gorini A, Pastoris O (1984) Cerebral and cerebellar metabolic changes induced by drugs during the recovery period after profound hypoglycemia. Farmaco Sci 39:44–56

    CAS  Google Scholar 

  171. Ronchetti F, Russo G, Bombardelli E, Bonati A (1971) A new alkaloid from Rauwolfia vomitoria. Phytochemistry 10:1385–1388

    Google Scholar 

  172. Campbell JIA, Mortensen A, Mølgaard P (2006) Tissue lipid lowering-effect of a traditional Nigerian anti-diabetic infusion of Rauwolfia vomitoria foilage and Citrus aurantium fruit. J Ethnopharmacol 104:379–386

    Google Scholar 

  173. Phan MG, Phan TS, Matsunami K, Otsuka H (2006) Chemical and biological evaluation on scopadulane-type diterpenoids from Scoparia dulcis of Vietnamese origin. Chem Pharm Bull (Tokyo) 54:546–549

    CAS  Google Scholar 

  174. Latha M, Pari L, Sitasawad S, Bhonde R (2004) Scoparia dulcis, a traditional anti-diabetic plant, protects against streptozotocin induced oxidative stress and apoptosis in vitro and in vivo. J Biochem Mol Toxicol 18:261–272

    CAS  Google Scholar 

  175. Ly TT, Hewitt J, Davey RJ, Lim EM, Davis EA, Jones TW (2011) Improving epinephrine responses in hypoglycemia unawareness with real-time continuous glucose monitoring in adolescents with type 1 diabetes. Diabetes Care 34:50–52

    Google Scholar 

  176. Andrews KM, Beebe D a, Benbow JW et al (2011) 1-((3S,4S)-4-amino-1-(4-substituted-1,3,5-triazin-2-yl) pyrrolidin-3-yl)-5,5-difluoropiperidin-2-one inhibitors of DPP-4 for the treatment of type 2 diabetes. Bioorg Med Chem Lett 21:1810–1814

    Google Scholar 

  177. Aguilar-Santamaría L, Ramírez G, Nicasio P, Alegría-Reyes C, Herrera-Arellano A (2009) Anti-diabetic activities of Tecoma stans (L.) Juss. ex Kunth. J Ethnopharmacol 124:284–288

    Google Scholar 

  178. Hammouda Y, Rashid A-K, Amer MS (1964) Hypoglycaemic properties of tecomine and tecostanine. J Pharm Pharmacol 16:833–834

    CAS  Google Scholar 

  179. Van de Venter M, Roux S, Bungu LC et al (2008) Anti-diabetic screening and scoring of 11 plants traditionally used in South Africa. J Ethnopharmacol 119:81–86

    Google Scholar 

  180. Torres JL, Bobet R (2001) New flavanol derivatives from grape (Vitis vinifera) byproducts. Antioxidant aminoethylthio–flavan-3-ol conjugates from a polymeric waste fraction used as a source of flavanols. J Agric Food Chem 49:4627–4634

    CAS  Google Scholar 

  181. Pinent M, Blay M, Bladé MC, Salvadó MJ, Arola L, Ardévol A (2004) Grape seed-derived procyanidins have an antihyperglycemic effect in streptozotocin-induced diabetic rats and insulinomimetic activity in insulin-sensitive cell lines. Endocrinology 145:4985–4990

    CAS  Google Scholar 

  182. Song E-K, Hur H, Han M-K (2003) Epigallocatechin gallate prevents autoimmune diabetes induced by multiple low doses of streptozotocin in mice. Arch Pharm Res 26:559–563

    CAS  Google Scholar 

  183. Takayama H, Okazaki T, Yamaguchi K, Aimi N, Haginiwa J et al (1988) Structure of two new diterpene alkaloids, 3-epi-ignavinol and 2,3-dehydrodelcosine. Chem Pharm Bull (Tokyo) 36(8):3210–3212

    CAS  Google Scholar 

  184. Konno C, Murayama M, Sugiyama K, Arai M, Murakami M, Takahashi M, Hikino H (1985) Isolation and hypoglycemic activity of aconitans A, B, C and D, glycans of Aconitum carmichaeli roots. Planta Med 51:160–161

    Google Scholar 

  185. Howes M, Simmonds M (2005) Plants used in the treatment of diabetes. In: Soumyanath A (ed) Traditional medicines for modern times. CRC, Boca Raton.

    Google Scholar 

  186. Zhang H, Wang X-N, Lin L-P, Ding J, Yue J-M (2007) Indole alkaloids from three species of the Ervatamia genus: E. officinalis, E. divaricata, and E. divaricata Gouyahua. J Nat Prod 70:54–59

    CAS  Google Scholar 

  187. Fujii M, Takei I, Umezawa K (2009) Anti-diabetic effect of orally administered conophylline-containing plant extract on streptozotocin-treated and Goto-Kakizaki rats. Biomed Pharmacother 63:710–716

    CAS  Google Scholar 

  188. Usubillaga A (1988) Solanudine, a steroidal alkaloid from Solanum nudum. Phytochemistry 27:3031–3032

    CAS  Google Scholar 

  189. Yoshikawa M, Nakamura S, Ozaki K, Kumahara A, Morikawa T, Matsuda H (2007) Structures of steroidal alkaloid oligoglycosides, robeneosides A and B, and antidiabetogenic constituents from the Brazilian medicinal plant Solanum lycocarpum. J Nat Prod 70:210–214

    CAS  Google Scholar 

  190. Villaseñor IM, Lamadrid MRA (2006) Comparative anti-hyperglycemic potentials of medicinal plants. J Ethnopharmacol 104:129–131

    Google Scholar 

  191. El Sayed KA, Hamann MT, Abd El-Rahman HA, Zaghloul AM (1998) New pyrrole alkaloids from Solanum sodomaeum. J Nat Prod 61:848–850

    CAS  Google Scholar 

  192. Kar DM, Maharana L, Pattnaik S, Dash GK (2006) Studies on hypoglycaemic activity of Solanum xanthocarpum Schrad. & Wendl. fruit extract in rats. J Ethnopharmacol 108:251–256

    CAS  Google Scholar 

  193. Kashiwaba N, Morooka S, Ono M, Toda J, Suzuki H et al (1997) Alkaloidal constituents of the leaves of Stephania cepharantha cultivated in Japan: structure of cephasugine, a new morphinane alkaloid. Chem Pharm Bull (Tokyo) 45(3):545–548

    CAS  Google Scholar 

  194. Mosihuzzaman M, Nahar N, Ali L, Rokeya B, Khan AK et al (1994) Hypoglycemic effects of three plants from eastern himalayan belt. Diabetes Res 26(3):127–138

    CAS  Google Scholar 

  195. Semwal DK, Rawat U, Semwal R, Singh R, Singh GJP (2010) Anti-hyperglycemic effect of 11-hydroxypalmatine, a palmatine derivative from Stephania glabra tubers. J Asian Nat Prod Res 12:99–105

    CAS  Google Scholar 

  196. Tsutsumi T, Kobayashi S, Liu YY, Kontani H (2003) Anti-hyperglycemic effect of fangchinoline Isolated from Stephania tetrandra radix in streptozotocin-diabetic mice. Biol Pharm Bull 26:313–317

    CAS  Google Scholar 

  197. Beek TAV, Verpoorte R, Svendsen AB (1984) Alkaloids of Tabernaemontana eglandulosa. Tetrahedron 40(4):737

    Google Scholar 

  198. Ma D-L, Chan DS-H, Leung C-H (2013) Drug repositioning by structure-based virtual screening. Chem Soc Rev 42:2130–2141

    CAS  Google Scholar 

  199. Meslamani J, Bhajun R, Martz F, Rognan D (2013) Computational profiling of bioactive compounds using a target-dependent composite workflow. J Chem Inf Model 53:2322–2333 doi:10.1021/ci400303n

    CAS  Google Scholar 

  200. Peng S, Lin X, Guo Z, Huang N (2012) Identifying multiple-target ligands via computational chemogenomics approaches. Curr Top Med Chem 12:1363–1375

    CAS  Google Scholar 

  201. Swamidass SJ, Lu Z, Agarwal P, Butte AJ (2014) Computational approaches to drug repurposing and pharmacolog- session introduction. Pac Symp Biocomput 19:110–113

    Google Scholar 

  202. Peters J-U (2013) Polypharmacology—foe or friend? J Med Chem 56:8955–8971

    CAS  Google Scholar 

  203. Santiago DN, Pevzner Y, Durand AA, Tran M, Scheerer RR, Daniel K, Sung S-S, Woodcock HL, Guida WC, Brooks WH (2012) Virtual target screening: validation using kinase inhibitors. J Chem Inf Model 52:2192–2203

    CAS  Google Scholar 

  204. Yue R, Shan L, Yang X, Zhang W (2012) Approaches to target profiling of natural products. Curr Med Chem 19:3841–3855

    CAS  Google Scholar 

  205. Gao Z, Li H, Zhang H, Liu X, Kang L, Luo X, Zhu W, Chen K, Wang X, Jiang H (2008) PDTD: a web-accessible protein database for drug target identification. BMC Bioinformatics 9:104

    Google Scholar 

  206. Li H, Gao Z, Kang L et al (2006) TarFisDock: a web server for identifying drug targets with docking approach. Nucleic Acids Res 34:W219–W224

    CAS  Google Scholar 

  207. Laskowski RA, Swindells MB (2011) LigPlot+: multiple ligand-protein interaction diagrams for drug discovery. J Chem Inf Model 51:2778–2786

    CAS  Google Scholar 

  208. Sayle RA, Milner-White EJ (1995) RASMOL: biomolecular graphics for all. Trends Biochem Sci 20:374

    CAS  Google Scholar 

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Ojeda, M., Cereto-Massagué, A., Valls, C., Pujadas, G., Pujadas, G. (2014). DPP-IV, An Important Target for Antidiabetic Functional Food Design. In: Martinez-Mayorga, K., Medina-Franco, J. (eds) Foodinformatics. Springer, Cham. https://doi.org/10.1007/978-3-319-10226-9_7

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