Molecular & Cellular Toxicology

, Volume 13, Issue 1, pp 1–20 | Cite as

Anti-diabetic effects of natural products an overview of therapeutic strategies

Review Paper

Abstract

Diabetes mellitus, a large part of metabolic disorder, is characterized by persistent hyperglycemia. The number of people suffering from diabetes is rapidly increasing worldwide, and the disease is often accompanied by severe complications such as heart disease, diabetic kidney failure, and retinal disease due to the high blood glucose levels over a long period of time. Comprehensive diabetic management is important, including efforts to lower the blood glucose level and body weight as well as to prevent insulin resistance. Although various prescriptions for diabetes have been used as therapeutic medicines, many researchers have long studied this disease in an effort to find new effective substances derived from natural products without side effects or toxicity. In the research on natural product, plants can have toxic or insufficient effects and unexplained outcomes, but the possibilities are unlimited. Here, we explain medicinal plants with anti-diabetic effects in a comprehensive manner, focusing on hormonal regulation and metabolic regulation, and describe active components and natural products based on the vast amount of research and on clinical trials. This review suggests that medicinal plants can used to treat diabetic mellitus through hormonal regulation and metabolic regulation as a therapeutic medication.

Keywords

Diabetes mellitus Anti-diabetes Natural product Therapeutic agent 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Shaw, J. E., Sicree, R. A. & Zimmet, P. Z. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 87:4–14 (2010).PubMedCrossRefGoogle Scholar
  2. 2.
    McNaughton, D. ‘Diabesity’ down under: overweight and obesity as cultural signifiers for type 2 diabetes mellitus. Critical Public Health 23:274–288 (2013).PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Schuit, F. C., Huypens, P., Heimberg, H. & Pipeleers, D. G. Glucose sensing in pancreatic beta-cells: a model for the study of other glucose-regulated cells in gut, pancreas, and hypothalamus. Diabetes 50:1–11 (2001).PubMedCrossRefGoogle Scholar
  4. 4.
    Leturque, A., Brot-Laroche, E. & Le Gall, M. GLUT2 mutations, translocation, and receptor function in diet sugar managing. Am J Physiol Endocrinol Metab 296:E985–992 (2009).PubMedCrossRefGoogle Scholar
  5. 5.
    MacDonald, P. E., Joseph, J. W. & Rorsman, P. Glucosesensing mechanisms in pancreatic beta-cells. Philos Trans R Soc Lond B Biol Sci 360:2211–2225 (2005).PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Drucker, D. J. et al. Incretin-based therapies for the treatment of type 2 diabetes: evaluation of the risks and benefits. Diabetes Care 33:428–433 (2010).PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Bailey, C. J. & Day, C. Metformin: its botanical background. Practical Diabetes Int 21:115–117 (2004).CrossRefGoogle Scholar
  8. 8.
    Patel, S. S. & Udayabanu, M. Effect of natural products on diabetes associated neurological disorders. Rev Neurosci, doi:10.1515/revneuro-2016–0038 (2016).Google Scholar
  9. 9.
    Dastagir, G. & Rizvi, M. A. Review - Glycyrrhiza glabra L. (Liquorice). Pak J Pharm Sci 29:1727–1733 (2016).PubMedGoogle Scholar
  10. 10.
    Arulselvan, P. et al. Antidiabetic therapeutics from natural source: A systematic review. Biomed Prev Nutr 4:607–617 (2014).CrossRefGoogle Scholar
  11. 11.
    Baggio, L. L. & Drucker, D. J. Biology of incretins: GLP-1 and GIP. Gastroenterology 132:2131–2157 (2007).PubMedCrossRefGoogle Scholar
  12. 12.
    Wu, T., Rayner, C. K., Jones, K. & Horowitz, M. Dietary effects on incretin hormone secretion. Vitam Horm 84:81–110 (2010).PubMedCrossRefGoogle Scholar
  13. 13.
    Kim, W. & Egan, J. M. The role of incretins in glucose homeostasis and diabetes treatment. Pharmacol Rev 60:470–512 (2008).PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Joo, E. et al. Inhibition of Gastric Inhibitory Polypeptide Receptor Signaling in Adipose Tissue Reduces Insulin Resistance and Hepatic Steatosis in High Fat Diet-Fed Mice. Diabetes, db160758 (2017).Google Scholar
  15. 15.
    Kim, K.-H. & Jang, H.-J. Development of GLP-1 secretagogue using microarray in enteroendocrine L cells. BioChip J, 10:272–276.Google Scholar
  16. 16.
    Kim, K. S. & Jang, H. J. Medicinal Plants Qua Glucagon-Like Peptide-1 Secretagogue via Intestinal Nutrient Sensors. eCAM 2015:71742 (2015).Google Scholar
  17. 17.
    Wang, X., Liu, H., Chen, J., Li, Y. & Qu, S. Multiple Factors Related to the Secretion of Glucagon-Like Peptide-1. Int J Endocrinol 2015:651757 (2015).PubMedPubMedCentralGoogle Scholar
  18. 18.
    Jang, H. J. et al. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A 104:15069–15074 (2007).PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Kokrashvili, Z., Mosinger, B. & Margolskee, R. F. Taste signaling elements expressed in gut enteroendocrine cells regulate nutrient-responsive secretion of gut hormones. Am J Clin Nutr 90:822s–825s (2009).PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Kokrashvili, Z. et al. Endocrine taste cells. Br J Nutr 111 Suppl 1:S23–29 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Ohtsu, Y. et al. Diverse signaling systems activated by the sweet taste receptor in human GLP-1-secreting cells. Mol Cell Endocrinol 394:70–79 (2014).PubMedCrossRefGoogle Scholar
  22. 22.
    Phuwamongkolwiwat, P., Hira, T. & Hara, H. A nondigestible saccharide, fructooligosaccharide, increases the promotive effect of a flavonoid, alpha-glucosyl-isoquercitrin, on glucagon-like peptide 1 (GLP-1) secretion in rat intestine and enteroendocrine cells. Molecular Nutrition & Food Research 58:1581–1584 (2014).CrossRefGoogle Scholar
  23. 23.
    Cho, C.-W. et al. Chemical composition characteristics of Korean straight ginseng products. Journal of Ethnic Foods 1:24–28 (2014).CrossRefGoogle Scholar
  24. 24.
    Luo, J. Z. & Luo, L. Ginseng on hyperglycemia: effects and mechanisms. eCAM 6:423–427 (2009).PubMedGoogle Scholar
  25. 25.
    Lee, S. M. et al. Characterization of Korean Red Ginseng (Panax ginseng Meyer): History, preparation method, and chemical composition. J Ginseng Res 39:384–391 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Liu, C. et al. Increased glucagon-like peptide-1 secretion may be involved in antidiabetic effects of ginsenosides. The Journal of Endocrinology 217:185–196 (2013).PubMedCrossRefGoogle Scholar
  27. 27.
    Kim, K. S. et al. The aglycone of ginsenoside Rg3 enables glucagon-like peptide-1 secretion in enteroendocrine cells and alleviates hyperglycemia in type 2 diabetic mice. Sci Rep 5:18325 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Sakamoto, E. et al. Ingestion of a moderate high-sucrose diet results in glucose intolerance with reduced liver glucokinase activity and impaired glucagon-like peptide-1 secretion. J Diabetes Investig 3:432–440 (2012).PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Jaggupilli, A., Howard, R., Upadhyaya, J. D., Bhullar, R. P. & Chelikani, P. Bitter taste receptors: Novel insights into the biochemistry and pharmacology. Int J Biochem Cell Biol 77:184–196 (2016).PubMedCrossRefGoogle Scholar
  30. 30.
    Shaik, F. A. et al. Bitter taste receptors: Extraoral roles in pathophysiology. Int J Biochem Cell Biol 77:197–204 (2016).PubMedCrossRefGoogle Scholar
  31. 31.
    Pydi, S. P., Bhullar, R. P. & Chelikani, P. Constitutive activity of bitter taste receptors (T2Rs). Adv Pharmacol 70:303–326 (2014).PubMedCrossRefGoogle Scholar
  32. 32.
    Chandrashekar, J. et al. T2Rs function as bitter taste receptors. Cell 100:703–711 (2000).PubMedCrossRefGoogle Scholar
  33. 33.
    Wu, S. V. et al. Expression of bitter taste receptors of the T2R family in the gastrointestinal tract and enteroendocrine STC-1 cells. Proc Natl Acad Sci U S A 99:2392–2397 (2002).PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Kim, K. S., Egan, J. M. & Jang, H. J. Denatonium induces secretion of glucagon-like peptide-1 through activation of bitter taste receptor pathways. Diabetologia 57:2117–2125 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Rozengurt, N. et al. Colocalization of the alpha-subunit of gustducin with PYY and GLP-1 in L cells of human colon. American Journal of Physiology. Gastrointestinal and Liver Physiology 291:G792–802 (2006).PubMedCrossRefGoogle Scholar
  36. 36.
    Clark, A. A., Liggett, S. B. & Munger, S. D. Extraoral bitter taste receptors as mediators of off-target drug effects. Faseb J 26:4827–4831 (2012).PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Deshpande, D. A. et al. Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. Nat Med 16:1299–1304 (2010).PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Liggett, S. B. Bitter taste receptors on airway smooth muscle as targets for novel bronchodilators. Expert Opin Ther Targets 17:721–731 (2013).PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Park, J. et al. GLP-1 secretion is stimulated by 1,10-phenanthroline via colocalized T2R5 signal transduction in human enteroendocrine L cell. Biochemical and Biophysical Research Communications 468:306–311 (2015).PubMedCrossRefGoogle Scholar
  40. 40.
    Dandawate, P. R., Subramaniam, D., Padhye, S. B. & Anant, S. Bitter melon: a panacea for inflammation and cancer. Chinese Journal of Natural Medicines 14:81–100 (2016).PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Hussan, F., Teoh, S. L., Muhamad, N., Mazlan, M. & Latiff, A. A. Momordica charantia ointment accelerates diabetic wound healing and enhances transforming growth factor-beta expression. J Wound Care 23:400, 402, 404–407 (2014).CrossRefGoogle Scholar
  42. 42.
    Raina, K., Kumar, D. & Agarwal, R. Promise of bitter melon (Momordica charantia) bioactives in cancer prevention and therapy. Semin Cancer Biol 40–41:116–129 (2016).PubMedCrossRefGoogle Scholar
  43. 43.
    Huang, T. N., Lu, K. N., Pai, Y. P., Chin, H. & Huang, C. J. Role of GLP-1 in the Hypoglycemic Effects of Wild Bitter Gourd. eCAM 2013:625892 (2013).PubMedPubMedCentralGoogle Scholar
  44. 44.
    Shin, M. H. et al. Hexane Fractions of Bupleurum falcatum L. Stimulates Glucagon-Like Peptide-1 Secretion through G beta gamma-Mediated Pathway. eCAM 2014:982165 (2014).PubMedPubMedCentralGoogle Scholar
  45. 45.
    Suh, H. W. et al. A bitter herbal medicine Gentiana scabra root extract stimulates glucagon-like peptide-1 secretion and regulates blood glucose in db/db mouse. Journal of Ethnopharmacology 172:219–226 (2015).PubMedCrossRefGoogle Scholar
  46. 46.
    Mennella, I. et al. Microencapsulated bitter compounds (from Gentiana lutea) reduce daily energy intakes in humans. Br J Nutr 1–10 (2016).Google Scholar
  47. 47.
    Abd El-Wahab, A. E., Ghareeb, D. A., Sarhan, E. E., Abu-Serie, M. M. & El Demellawy, M. A. In vitro biological assessment of Berberis vulgaris and its active constituent, berberine: antioxidants, anti-acetylcholinesterase, anti-diabetic and anticancer effects. BMC Complement Altern Med 13:218 (2013).PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Pang, B. et al. Application of berberine on treating type 2 diabetes mellitus. International Journal of Endocrinology 2015:905749 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Chang, W., Chen, L. & Hatch, G. M. Berberine as a therapy for type 2 diabetes and its complications: From mechanism of action to clinical studies. Biochem Cell Biol 93:479–486 (2015).PubMedCrossRefGoogle Scholar
  50. 50.
    Cui, G. et al. Berberine differentially modulates the activities of ERK, p38 MAPK, and JNK to suppress Th17 and Th1 T cell differentiation in type 1 diabetic mice. J Biol Chem 284:28420–28429 (2009).PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Zhang, X. et al. Protective Effects of Berberine on Renal Injury in Streptozotocin (STZ)-Induced Diabetic Mice. Int J Mol Sci 17:1327 (2016).PubMedCentralCrossRefGoogle Scholar
  52. 52.
    Imenshahidi, M. & Hosseinzadeh, H. Berberis Vulgaris and Berberine: An Update Review. Phytother Res 30:1745–1764 (2016).PubMedCrossRefGoogle Scholar
  53. 53.
    Yu, Y. et al. Berberine induces GLP-1 secretion through activation of bitter taste receptor pathways. Biochem Pharmacol 97:173–177 (2015).PubMedCrossRefGoogle Scholar
  54. 54.
    Yu, Y. et al. Modulation of glucagon-like peptide-1 release by berberine: in vivo and in vitro studies. Biochem Pharmacol 79:1000–1006 (2010).PubMedCrossRefGoogle Scholar
  55. 55.
    Kim, K.-H. et al. Aqueous extracts of Anemarrhena asphodeloides stimulate glucagon-like pepetide-1 secretion in enteroendocrine NCI-H716 cells. BioChip J 7:188–193 (2013).CrossRefGoogle Scholar
  56. 56.
    Kim, K.-S. et al. Transcriptomic analysis of the bitter taste receptor-mediated glucagon-like peptide-1 stimulation effect of quinine. BioChip J 7:386–392 (2013).CrossRefGoogle Scholar
  57. 57.
    Choi, E.-K. et al. Hexane fraction of Citrus aurantium L. stimulates glucagon-like peptide-1 (GLP-1) secretion via membrane depolarization in NCI-H716 cells. BioChip J 6:41–47 (2012).CrossRefGoogle Scholar
  58. 58.
    Lauffer, L. M., Iakoubov, R. & Brubaker, P. L. GPR119 is essential for oleoylethanolamide-induced glucagonlike peptide-1 secretion from the intestinal enteroendocrine L-cell. Diabetes 58:1058–1066 (2009).PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Park, E. Y. et al. Angelica dahurica Extracts Improve Glucose Tolerance through the Activation of GPR119. PloS One 11:e0158796 (2016).PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Fujii, Y., Osaki, N., Hase, T. & Shimotoyodome, A. Ingestion of coffee polyphenols increases postprandial release of the active glucagon-like peptide-1 (GLP-1(7–36)) amide in C57BL/6J mice. J Nutr Sci 4:e9 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Kim, K., Park, M., Lee, Y. M., Rhyu, M. R. & Kim, H. Y. Ginsenoside metabolite compound K stimulates glucagon-like peptide-1 secretion in NCI-H716 cells via bile acid receptor activation. Arch Pharm Res 37:1193–1200 (2014).PubMedCrossRefGoogle Scholar
  62. 62.
    Stenblom, E. L., Egecioglu, E., Landin-Olsson, M. & Erlanson-Albertsson, C. Consumption of thylakoidrich spinach extract reduces hunger, increases satiety and reduces cravings for palatable food in overweight women. Appetite 91:209–219 (2015).PubMedCrossRefGoogle Scholar
  63. 63.
    Stenblom, E. L. et al. Supplementation by thylakoids to a high carbohydrate meal decreases feelings of hunger, elevates CCK levels and prevents postprandial hypoglycaemia in overweight women. Appetite 68:118–123 (2013).PubMedCrossRefGoogle Scholar
  64. 64.
    Kohnke, R. et al. Thylakoids promote release of the satiety hormone cholecystokinin while reducing insulin in healthy humans. Scandinavian Journal of Gastroenterology 44:712–719 (2009).PubMedCrossRefGoogle Scholar
  65. 65.
    Nagamine, R. et al. Dietary sweet potato (Ipomoea batatas L.) leaf extract attenuates hyperglycaemia by enhancing the secretion of glucagon-like peptide-1 (GLP-1). Food Funct 5:2309–2316 (2014).PubMedCrossRefGoogle Scholar
  66. 66.
    Liu, Y. X. et al. Effects and molecular mechanisms of the antidiabetic fraction of Acorus calamus L. on GLP-1 expression and secretion in vivo and in vitro. J Ethnopharmacol 166:168–175 (2015).PubMedCrossRefGoogle Scholar
  67. 67.
    Liu, S. H., Chang, Y. H. & Chiang, M. T. Chitosan reduces gluconeogenesis and increases glucose uptake in skeletal muscle in streptozotocin-induced diabetic rats. J Agric Food Chem 58:5795–5800 (2010).PubMedCrossRefGoogle Scholar
  68. 68.
    Liu, S. H., Huang, Y. W., Wu, C. T., Chiu, C. Y. & Chiang, M. T. Low molecular weight chitosan accelerates glucagon-like peptide-1 secretion in human intestinal endocrine cells via a p38-dependent pathway. J Agric Food Chem 61:4855–4861 (2013).PubMedCrossRefGoogle Scholar
  69. 69.
    Kim, K.-S. et al. The effects of complex herbal medicine composed of Cornus fructus, Dioscoreae rhizoma, Aurantii fructus, and Mori folium in obese type-2 diabetes mice model. Orent Pharm Exp Med 13:69–75 (2013).CrossRefGoogle Scholar
  70. 70.
    Lee, I. S. et al. Antihyperglycemic and Antiobesity Effects of JAL2 on db/db Mice. eCAM 2016:6828514 (2016).PubMedPubMedCentralGoogle Scholar
  71. 71.
    Fu, Z., Gilbert, E. R. & Liu, D. Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Curr Diabetes Rev 9:25–53 (2013).PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Kojima, I. & Nakagawa, Y. The Role of the Sweet Taste Receptor in Enteroendocrine Cells and Pancreatic beta-Cells. Diabetes Metab J 35:451–457 (2011).PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Nakagawa, Y. et al. Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion. PloS One 4:e5106 (2009).PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Lemaire, K. & Schuit, F. Integrating insulin secretion and ER stress in pancreatic beta-cells. Nat Cell Biol 14:979–981 (2012).PubMedCrossRefGoogle Scholar
  75. 75.
    Laffitte, A., Neiers, F. & Briand, L. Functional roles of the sweet taste receptor in oral and extraoral tissues. Curr Opin Clin Nutr Metab Care 17:379–385 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Nakagawa, Y. et al. Multimodal function of the sweet taste receptor expressed in pancreatic beta-cells: generation of diverse patterns of intracellular signals by sweet agonists. Endocr J 60:1191–1206 (2013).PubMedCrossRefGoogle Scholar
  77. 77.
    Cui, J. et al. Insulin-secretagogue activity of eleven plant extracts and twelve pure compounds isolated from Aralia taibaiensis. Life Sci 92:131–136 (2013).PubMedCrossRefGoogle Scholar
  78. 78.
    Cui, J. et al. Insulinotropic effect of Chikusetsu saponin IVa in diabetic rats and pancreatic beta-cells. J Ethnopharmacol 164:334–339 (2015).PubMedCrossRefGoogle Scholar
  79. 79.
    Huang, C. F. et al. Extract of lotus leaf (Nelumbo nucifera) and its active constituent catechin with insulin secretagogue activity. J Agric Food Chem 59:1087–1094 (2011).PubMedCrossRefGoogle Scholar
  80. 80.
    Zheng, J. et al. Corydalis edulis Maxim. Promotes Insulin Secretion via the Activation of Protein Kinase Cs (PKCs) in Mice and Pancreatic beta Cells. Scientific Reports 7:40454 (2017).PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Schmidt, S. et al. Extracts from Leonurus sibiricus L. increase insulin secretion and proliferation of rat INS-1E insulinoma cells. J Ethnopharmacol 150:85–94 (2013).PubMedCrossRefGoogle Scholar
  82. 82.
    Vaidya, H. B., Ahmed, A. A., Goyal, R. K. & Cheema, S. K. Glycogen phosphorylase-a is a common target for anti-diabetic effect of iridoid and secoiridoid glycosides. J Pharm Pharm Sci 16:530–540 (2013).PubMedCrossRefGoogle Scholar
  83. 83.
    Pitschmann, A. et al. Quantitation of phenylpropanoids and iridoids in insulin-sensitising extracts of Leonurus sibiricus L. (Lamiaceae). Phytochem Anal 27:23–31 (2016).PubMedCrossRefGoogle Scholar
  84. 84.
    Kittl, M. et al. Quercetin Stimulates Insulin Secretion and Reduces the Viability of Rat INS-1 Beta-Cells. Cell Physiol Biochem 39:278–293 (2016).PubMedCrossRefGoogle Scholar
  85. 85.
    Latha, M., Pari, L., Sitasawad, S. & Bhonde, R. Insulin-secretagogue activity and cytoprotective role of the traditional antidiabetic plant Scoparia dulcis (Sweet Broomweed). Life Sci 75:2003–2014 (2004).PubMedCrossRefGoogle Scholar
  86. 86.
    Ramadan, B. K., Schaalan, M. F. & Tolba, A. M. Hypoglycemic and pancreatic protective effects of Portulaca oleracea extract in alloxan induced diabetic rats. BMC Complement Altern Med 17:37 (2017).PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Aljohi, A., Matou-Nasri, S. & Ahmed, N. Antiglycation and Antioxidant Properties of Momordica charantia. PloS One 11:e0159985 (2016).PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Sitasawad, S. L., Shewade, Y. & Bhonde, R. Role of bittergourd fruit juice in stz-induced diabetic state in vivo and in vitro. J Ethnopharmacol 73:71–79 (2000).PubMedCrossRefGoogle Scholar
  89. 89.
    Rathi, S. S., Grover, J. K., Vikrant, V. & Biswas, N. R. Prevention of experimental diabetic cataract by Indian Ayurvedic plant extracts. Phytother Res 16:774–777 (2002).PubMedCrossRefGoogle Scholar
  90. 90.
    El Awdan, S. A. et al. Hypoglycemic activity of Gleditsia caspica extract and its saponin-containing fraction in streptozotocin-induced diabetic rats. Z Naturforsch C 71:253–260 (2016).PubMedCrossRefGoogle Scholar
  91. 91.
    Keller, A. C. et al. Saponins from the traditional medicinal plant Momordica charantia stimulate insulin secretion in vitro. Phytomedicine 19:32–37 (2011).PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Xiang, L., Huang, X., Chen, L., Rao, P. & Ke, L. The reparative effects of Momordica Charantia Linn. extract on HIT-T15 pancreatic beta-cells. Asia Pac J Clin Nutr 16 Suppl 1:249–252 (2007).PubMedGoogle Scholar
  93. 93.
    Yousaf, S., Hussain, A., Rehman, S., Aslam, M. S. & Abbas, Z. Hypoglycemic and hypolipidemic effects of Lactobacillus fermentum, fruit extracts of Syzygium cumini and Momordica charantia on diabetes induced mice. Pak J Pharm Sci 29:1535–1540 (2016).PubMedGoogle Scholar
  94. 94.
    Harinantenaina, L. et al. Momordica charantia constituents and antidiabetic screening of the isolated major compounds. Chem Pharm Bull (Tokyo) 54:1017–1021 (2006).CrossRefGoogle Scholar
  95. 95.
    Raman, A. & Lau, C. Anti-diabetic properties and phytochemistry of Momordica charantia L. (Cucurbitaceae). Phytomedicine 2:349–362 (1996).PubMedCrossRefGoogle Scholar
  96. 96.
    Krawinkel, M. B. & Keding, G. B. Bitter gourd (Momordica Charantia): A dietary approach to hyperglycemia. Nutr Rev 64:331–337 (2006).PubMedCrossRefGoogle Scholar
  97. 97.
    Patel, R. et al. Analgesic and antipyretic activities of Momordica charantia Linn. fruits. J Adv Pharm Technol Res 1:415–418 (2010).PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Hazarika, R., Parida, P., Neog, B. & Yadav, R. N. Binding Energy calculation of GSK-3 protein of Human against some anti-diabetic compounds of Momordica charantia linn (Bitter melon). Bioinformation 8:251–254 (2012).PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Wang, H. Y. et al. Differential anti-diabetic effects and mechanism of action of charantin-rich extract of Taiwanese Momordica charantia between type 1 and type 2 diabetic mice. Food Chem Toxicol 69:347–356 (2014).PubMedCrossRefGoogle Scholar
  100. 100.
    Miura, T. et al. Impairment of insulin-stimulated GLUT4 translocation in skeletal muscle and adipose tissue in the Tsumura Suzuki obese diabetic mouse: a new genetic animal model of type 2 diabetes. Eur J Endocrinol 145:785–790 (2001).PubMedCrossRefGoogle Scholar
  101. 101.
    Kim, J. H., Pan, J. H., Cho, H. T. & Kim, Y. J. Black Ginseng Extract Counteracts Streptozotocin-Induced Diabetes in Mice. PloS One 11:e0146843 (2016).PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Seo, Y. S. et al. Black ginseng extract exerts anti-hyperglycemic effect via modulation of glucose metabolism in liver and muscle. J Ethnopharmacol 190:231–240 (2016).PubMedCrossRefGoogle Scholar
  103. 103.
    Luo, J. Z. & Luo, L. American ginseng stimulates insulin production and prevents apoptosis through regulation of uncoupling protein-2 in cultured beta cells. eCAM 3:365–372 (2006).PubMedPubMedCentralGoogle Scholar
  104. 104.
    Yoo, K. M., Lee, C., Lo, Y. M. & Moon, B. The hypoglycemic effects of American red ginseng (Panax quinquefolius L.) on a diabetic mouse model. J Food Sci 77:H147–152 (2012).PubMedCrossRefGoogle Scholar
  105. 105.
    Oshima, Y., Sato, K. & Hikino, H. Isolation and hypoglycemic activity of quinquefolans A, B, and C, glycans of Panax quinquefolium roots. J Nat Prod 50:188–190 (1987).PubMedCrossRefGoogle Scholar
  106. 106.
    Yang, H. J. et al. Anti-Diabetic Activities of Gastrodia elata Blume Water Extracts Are Mediated Mainly by Potentiating Glucose-Stimulated Insulin Secretion and Increasing beta-Cell Mass in Non-Obese Type 2 Diabetic Animals. Nutrients 8:161 (2016).PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Tanaka, S., Kanazawa, I., Notsu, M. & Sugimoto, T. Visceral fat obesity increases serum DPP-4 levels in men with type 2 diabetes mellitus. Diabetes Res Clin Pract 116:1–6 (2016).PubMedCrossRefGoogle Scholar
  108. 108.
    Aso, Y. et al. Serum level of soluble CD26/dipeptidyl peptidase-4 (DPP-4) predicts the response to sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes controlled inadequately by metformin and/or sulfonylurea. Transl Res 159:25–31 (2012).PubMedCrossRefGoogle Scholar
  109. 109.
    Lee, S. A. et al. CD26/DPP4 levels in peripheral blood and T cells in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 98:2553–2561 (2013).PubMedCrossRefGoogle Scholar
  110. 110.
    Wu, S., Hopper, I., Skiba, M. & Krum, H. Dipeptidyl peptidase-4 inhibitors and cardiovascular outcomes: meta-analysis of randomized clinical trials with 55,141 participants. Cardiovasc Ther 32:147–158 (2014).PubMedCrossRefGoogle Scholar
  111. 111.
    Elgendy, I. Y. et al. Cardiovascular Safety of Dipeptidyl-Peptidase IV Inhibitors: A Meta-Analysis of Placebo-Controlled Randomized Trials. Am J Cardiovasc Drugs, doi:10.1007/s40256–016-0208-x (2016).Google Scholar
  112. 112.
    Ou, H. T., Chang, K. C., Li, C. Y. & Wu, J. S. Comparative cardiovascular risks of dipeptidyl peptidase-4 inhibitors with other 2nd and 3rd line antidiabetic drugs in patients with type 2 diabetes. Br J Clin Pharmacol, doi:10.1111/bcp.13241 (2017).Google Scholar
  113. 113.
    El-Ouaghlidi, A. et al. The dipeptidyl peptidase 4 inhibitor vildagliptin does not accentuate glibenclamideinduced hypoglycemia but reduces glucose-induced glucagon-like peptide 1 and gastric inhibitory polypeptide secretion. J Clin Endocrinol Metab 92:4165–4171 (2007).PubMedCrossRefGoogle Scholar
  114. 114.
    Shi, S., Koya, D. & Kanasaki, K. Dipeptidyl peptidase-4 and kidney fibrosis in diabetes. Fibrogenesis Tissue Repair 9:1 (2016).PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Alam, M. A., Chowdhury, M. R., Jain, P., Sagor, M. A. & Reza, H. M. DPP-4 inhibitor sitagliptin prevents inflammation and oxidative stress of heart and kidney in two kidney and one clip (2K1C) rats. Diabetol Metab Syndr 7:107 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Bansal, P. et al. Antidiabetic, antihyperlipidemic and antioxidant effects of the flavonoid rich fraction of Pilea microphylla (L.) in high fat diet/streptozotocin-induced diabetes in mice. Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft fur Toxikologische Pathologie 64:651–658 (2012).CrossRefGoogle Scholar
  117. 117.
    Kozuka, M. et al. Identification and characterization of a dipeptidyl peptidase IV inhibitor from aronia juice. Biochem Biophys Res Commun 465:433–436 (2015).PubMedCrossRefGoogle Scholar
  118. 118.
    Kosaraju, J. et al. A molecular connection of Pterocarpus marsupium, Eugenia jambolana and Gymnema sylvestre with dipeptidyl peptidase-4 in the treatment of diabetes. Pharm Biol 52:268–271 (2014).PubMedCrossRefGoogle Scholar
  119. 119.
    Belle, L. P. et al. 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 (2013).PubMedCrossRefGoogle Scholar
  120. 120.
    Purnomo, Y., Soeatmadji, D. W., Sumitro, S. B. & Widodo, M. A. Anti-diabetic potential of Urena lobata leaf extract through inhibition of dipeptidyl peptidase IV activity. Asian Pac J Trop Biomed 5:645–649 (2015).CrossRefGoogle Scholar
  121. 121.
    Gonzalez-Abuin, N. et al. Grape seed-derived procyanidins decrease dipeptidyl-peptidase 4 activity and expression. J Agric Food Chem 60:9055–9061 (2012).PubMedCrossRefGoogle Scholar
  122. 122.
    Saleem, S. et al. Plants Fagonia cretica L. and Hedera nepalensis K. Koch contain natural compounds with potent dipeptidyl peptidase-4 (DPP-4) inhibitory activity. J Ethnopharmacol 156:26–32 (2014).PubMedCrossRefGoogle Scholar
  123. 123.
    Sharma, B. R. & Rhyu, D. Y. Anti-diabetic effects of Caulerpa lentillifera: stimulation of insulin secretion in pancreatic beta-cells and enhancement of glucose uptake in adipocytes. Asian Pac J Trop Biomed 4:575–580 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Sharma, B. R., Kim, H. J. & Rhyu, D. Y. Caulerpa lentillifera extract ameliorates insulin resistance and regulates glucose metabolism in C57BL/KsJ-db/db mice via PI3K/AKT signaling pathway in myocytes. J Transl Med 13:62 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Gu, L. H. et al. A thin-layer chromatography-bioautographic method for detecting dipeptidyl peptidase IV inhibitors in plants. J Chromatogr A 1411:116–122 (2015).PubMedCrossRefGoogle Scholar
  126. 126.
    Permatasari, Y. I. Antidiabetic Activity and Phytochemical Screening of Extracts from Indonesian Plants by Inhibition of Alpha Amylase, Alpha Glucosidase and Dipeptidyl Peptidase IV. PJBS 18:279–284 (2015).Google Scholar
  127. 127.
    Bower, A. M., Real Hernandez, L. M., Berhow, M. A. & de Mejia, E. G. Bioactive compounds from culinary herbs inhibit a molecular target for type 2 diabetes management, dipeptidyl peptidase IV. J Agric Food Chem 62:6147–6158 (2014).PubMedCrossRefGoogle Scholar
  128. 128.
    Cicero, A. F. & Tartagni, E. Antidiabetic properties of berberine: from cellular pharmacology to clinical effects. Hosp Pract (1995) 40:56–63 (2012).CrossRefGoogle Scholar
  129. 129.
    Wang, J., Dai, G. & Li, W. [Berberine regulates glycemia via local inhibition of intestinal dipeptidyl peptidase-]. Zhejiang Da Xue Xue Bao Yi Xue Ban 45:486–492 (2016).PubMedGoogle Scholar
  130. 130.
    Al-masri, I. M., Mohammad, M. K. & Tahaa, M. O. 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 (2009).PubMedCrossRefGoogle Scholar
  131. 131.
    Peng, C. H. et al. Hibiscus sabdariffa polyphenols alleviate insulin resistance and renal epithelial to mesenchymal transition: a novel action mechanism mediated by type 4 dipeptidyl peptidase. J Agric Food Chem 62:9736–9743 (2014).PubMedCrossRefGoogle Scholar
  132. 132.
    Huang, C. N., Wang, C. J., Yang, Y. S., Lin, C. L. & Peng, C. H. Hibiscus sabdariffa polyphenols prevent palmitate-induced renal epithelial mesenchymal transition by alleviating dipeptidyl peptidase-4-mediated insulin resistance. Food Funct 7:475–482 (2016).PubMedCrossRefGoogle Scholar
  133. 133.
    Wang, Z. S. et al. Astragaloside IV attenuates proteinuria in streptozotocin-induced diabetic nephropathy via the inhibition of endoplasmic reticulum stress. BMC Nephrol 16:44 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Shahzad, M. et al. Protection against oxidative stressinduced apoptosis in kidney epithelium by Angelica and Astragalus. J Ethnopharmacol 179:412–419 (2016).PubMedCrossRefGoogle Scholar
  135. 135.
    Tangvarasittichai, S. Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World J Diabetes 6:456–480 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Bestermann, W. et al. Addressing the global cardiovascular risk of hypertension, dyslipidemia, diabetes mellitus, and the metabolic syndrome in the southeastern United States, part II: treatment recommendations for management of the global cardiovascular risk of hypertension, dyslipidemia, diabetes mellitus, and the metabolic syndrome. Am J Med Sci 329:292–305 (2005).PubMedCrossRefGoogle Scholar
  137. 137.
    Eckel, R. H. et al. Obesity and type 2 diabetes: what can be unified and what needs to be individualized? Diabetes Care 34:1424–1430 (2011).PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Weyer, C. et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930–1935 (2001).PubMedCrossRefGoogle Scholar
  139. 139.
    Hajer, G. R., van Haeften, T. W. & Visseren, F. L. Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J 29:2959–2971 (2008).PubMedCrossRefGoogle Scholar
  140. 140.
    Boden, G. & Shulman, G. Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and β-cell dysfunction. Eur J Clin Invest 32:14–23 (2002).PubMedCrossRefGoogle Scholar
  141. 141.
    Kahn, S. E., Hull, R. L. & Utzschneider, K. M. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444:840–846 (2006).PubMedCrossRefGoogle Scholar
  142. 142.
    Lowell, B. B. & Shulman, G. I. Mitochondrial dysfunction and type 2 diabetes. Science 307:384–387 (2005).PubMedCrossRefGoogle Scholar
  143. 143.
    Zhou, G. et al. Role of AMP-activated protein kinase in mechanism of metformin action. Eur J Clin Invest 108:1167–1174 (2001).CrossRefGoogle Scholar
  144. 144.
    Mazzotti, A., Caletti, M. T., Marchignoli, F., Forlani, G. & Marchesini, G. Which treatment for type 2 diabetes associated with non-alcoholic fatty liver disease? Dig Liver Dis 491:235–240 (2016).Google Scholar
  145. 145.
    Fujita, Y. & Inagaki, N. Metformin: New Preparations and Nonglycemic Benefits. Curr Diab Rep 17:5 (2017).PubMedCrossRefGoogle Scholar
  146. 146.
    Evans, J. M., Donnelly, L. A., Emslie-Smith, A. M., Alessi, D. R. & Morris, A. D. Metformin and reduced risk of cancer in diabetic patients. Bmj 330:1304–1305 (2005).PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Hermann, L. Metformin: a review of its pharmacological properties and therapeutic use. Diabetes Metab 5:233–245 (1979).Google Scholar
  148. 148.
    Aleman-Gonzalez-Duhart, D., Tamay-Cach, F., Alvarez-Almazan, S. & Mendieta-Wejebe, J. E. Current Advances in the Biochemical and Physiological Aspects of the Treatment of Type 2 Diabetes Mellitus with Thiazolidinediones. PPAR Res 2016:7614270 (2016).PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Lewis, J. D. et al. Pioglitazone use and risk of bladder cancer and other common cancers in persons with diabetes. Jama 314:265–277 (2015).PubMedCrossRefGoogle Scholar
  150. 150.
    Leng, W. & Ouyang, X. The SGLT-2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE-/-Mice. Mediators Inflamm 2016:6305735 (2016).PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Rahman, A., Hitomi, H. & Nishiyama, A. Cardioprotective effects of SGLT2 inhibitors are possibly associated with normalization of the circadian rhythm of blood pressure. Hypertens Res, doi:10.1038/hr.2016. 193 (2017).Google Scholar
  152. 152.
    Mosley, J. F., 2nd, Smith, L., Everton, E. & Fellner, C. Sodium-Glucose Linked Transporter 2 (SGLT2) Inhibitors in the Management Of Type-2 Diabetes: A Drug Class Overview. P t 40:451–462 (2015).PubMedPubMedCentralGoogle Scholar
  153. 153.
    Choi, C. I. Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors from Natural Products: Discovery of Next-Generation Antihyperglycemic Agents. Molecules 21, doi:10.3390/molecules21091136 (2016).Google Scholar
  154. 154.
    Scheen, A. J. SGLT2 Inhibitors: Benefit/Risk Balance. Curr Diab Rep 16:92 (2016).PubMedCrossRefGoogle Scholar
  155. 155.
    Montane, J., Cadavez, L. & Novials, A. Stress and the inflammatory process: a major cause of pancreatic cell death in type 2 diabetes. Diabetes Metab Syndr Obes 7:25–34 (2014).PubMedPubMedCentralGoogle Scholar
  156. 156.
    Tomita, T. Apoptosis in pancreatic β-islet cells in Type 2 diabetes. Bosn J Basic Med Sci 16:162 (2016).PubMedPubMedCentralGoogle Scholar
  157. 157.
    Tomita, T. Immunocytochemical localisation of caspase-3 in pancreatic islets from type 2 diabetic subjects. Pathology 42:432–437 (2010).PubMedCrossRefGoogle Scholar
  158. 158.
    Sebai, H. et al. Lavender (Lavandula stoechas L.) essential oils attenuate hyperglycemia and protect against oxidative stress in alloxan-induced diabetic rats. Lipids Health Dis 12:189 (2013).PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Talpur, N., Echard, B., Ingram, C., Bagchi, D. & Preuss, H. Effects of a novel formulation of essential oils on glucose-insulin metabolism in diabetic and hypertensive rats: a pilot study. Diabetes Obes Metab 7:193–199 (2005).PubMedCrossRefGoogle Scholar
  160. 160.
    Duan, J. et al. Aralia taibaiensis Protects Cardiac Myocytes against High Glucose-Induced Oxidative Stress and Apoptosis. Am J Chin Med 43:1159–1175 (2015).PubMedCrossRefGoogle Scholar
  161. 161.
    Wang, Y. et al. Formononetin attenuates IL-1beta-induced apoptosis and NF-kappaB activation in INS-1 cells. Molecules 17:10052–10064 (2012).PubMedCrossRefGoogle Scholar
  162. 162.
    Li, R. J., Qiu, S. D., Chen, H. X., Tian, H. & Liu, G. Q. Effect of Astragalus polysaccharide on pancreatic cell mass in type 1 diabetic mice. Zhongguo Zhong Yao Za Zhi 32:2169–2173 (2007).PubMedGoogle Scholar
  163. 163.
    Saxena, A. & Vikram, N. K. Role of selected Indian plants in management of type 2 diabetes: a review. J Altern Complement Med 10:369–378 (2004).PubMedCrossRefGoogle Scholar
  164. 164.
    Abdollahi, M., Zuki, A. B., Goh, Y. M., Rezaeizadeh, A. & Noordin, M. M. Effects of Momordica charantia on pancreatic histopathological changes associated with streptozotocin-induced diabetes in neonatal rats. Histol Histopathol 26:13–21 (2011).PubMedGoogle Scholar
  165. 165.
    Halagappa, K., Girish, H. N. & Srinivasan, B. P. The study of aqueous extract of Pterocarpus marsupium Roxb. on cytokine TNF-alpha in type 2 diabetic rats. Indian J Pharmacol 42:392–396 (2010).PubMedPubMedCentralCrossRefGoogle Scholar
  166. 166.
    Liu, Y. W. et al. Ginsenoside Re attenuates diabetesassociated cognitive deficits in rats. Pharmacol Biochem Behav 101:93–98 (2012).PubMedCrossRefGoogle Scholar
  167. 167.
    Yuan, H. D., Kim, J. T., Kim, S. H. & Chung, S. H. Ginseng and diabetes: the evidences from in vitro, animal and human studies. J Ginseng Res 36:27–39 (2012).PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Sun, C. et al. Anti-hyperglycemic and anti-oxidative activities of ginseng polysaccharides in STZ-induced diabetic mice. Food Funct 5:845–848 (2014).PubMedCrossRefGoogle Scholar
  169. 169.
    Shih, C. C., Lin, C. H. & Lin, W. L. Effects of Momordica charantia on insulin resistance and visceral obesity in mice on high-fat diet. Diabetes Res Clin Pract 81:134–143 (2008).PubMedCrossRefGoogle Scholar
  170. 170.
    Bao, B. et al. Momordica charantia (Bitter Melon) reduces obesity-associated macrophage and mast cell infiltration as well as inflammatory cytokine expression in adipose tissues. PloS One 8:e84075 (2013).PubMedPubMedCentralCrossRefGoogle Scholar
  171. 171.
    Li, Z., Geng, Y.-N., Jiang, J.-D. & Kong, W.-J. Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus. eCAM 2014 (2014).Google Scholar
  172. 172.
    Komiyama, Y. et al. IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J Immunol 177:566–573 (2006).PubMedCrossRefGoogle Scholar
  173. 173.
    Raz, I., Eldor, R., Cernea, S. & Shafrir, E. Diabetes: insulin resistance and derangements in lipid metabolism. Cure through intervention in fat transport and storage. Diabetes Metab Res Rev 21:3–14 (2005).PubMedCrossRefGoogle Scholar
  174. 174.
    Yun, S. N., Moon, S. J., Ko, S. K., Im, B. O. & Chung, S. H. Wild ginseng prevents the onset of high-fat diet induced hyperglycemia and obesity in ICR mice. Arch Pharm Res 27:790–796 (2004).PubMedCrossRefGoogle Scholar
  175. 175.
    Hwang, J. T. et al. Anti-obesity effects of ginsenoside Rh2 are associated with the activation of AMPK signaling pathway in 3T3-L1 adipocyte. Biochem Biophys Res Commun 364:1002–1008 (2007).PubMedCrossRefGoogle Scholar
  176. 176.
    Quan, H. Y. et al. Ginsenoside Re lowers blood glucose and lipid levels via activation of AMP-activated protein kinase in HepG2 cells and high-fat diet fed mice. Int J Mol Med 29:73–80 (2012).PubMedGoogle Scholar
  177. 177.
    Cho, W. C. et al. Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats. Eur J Pharmacol 550:173–179 (2006).PubMedCrossRefGoogle Scholar
  178. 178.
    Gao, Y. et al. Ginsenoside Re reduces insulin resistance through activation of PPAR-gamma pathway and inhibition of TNF-alpha production. J Ethnopharmacol 147:509–516 (2013).PubMedCrossRefGoogle Scholar
  179. 179.
    Kiho, T. et al. Antidiabetic effect of an acidic polysaccharide (TAP) from Tremella aurantia and its degradation product (TAP-H). Biol Pharm Bull 24:1400–1403 (2001).PubMedCrossRefGoogle Scholar
  180. 180.
    Chen, Z. H. et al. Saponins isolated from the root of Panax notoginseng showed significant anti-diabetic effects in KK-Ay mice. Am J Chin Med 36:939–951 (2008).PubMedCrossRefGoogle Scholar
  181. 181.
    El Barky, A. R., Hussein, S. A., Alm-Eldeen, A. A., Hafez, Y. A. & Mohamed, T. M. Anti-diabetic activity of Holothuria thomasi saponin. Biomed Pharmacother 84:1472–1487 (2016).PubMedCrossRefGoogle Scholar
  182. 182.
    Shao, X. et al. Protective effect of compound K on diabetic rats. Nat Prod Commun 10:243–245 (2015).PubMedGoogle Scholar
  183. 183.
    Chung, M. J., Cho, S. Y., Bhuiyan, M. J., Kim, K. H. & Lee, S. J. Anti-diabetic effects of lemon balm (Melissa officinalis) essential oil on glucose-and lipid-regulating enzymes in type 2 diabetic mice. Br J Nutr 104:180–188 (2010).PubMedCrossRefGoogle Scholar
  184. 184.
    Yuan, L., Tu, D., Ye, X. & Wu, J. Hypoglycemic and hypocholesterolemic effects of Coptis chinensis franch inflorescence. Plant Foods Hum Nutr 61:139–144 (2006).PubMedCrossRefGoogle Scholar
  185. 185.
    Erejuwa, O. O., Sulaiman, S. A. & Wahab, M. S. Honey-a novel antidiabetic agent. Int J Biol Sci 8:913–934 (2012).PubMedPubMedCentralCrossRefGoogle Scholar
  186. 186.
    Bahrami, M. et al. Effects of natural honey consumption in diabetic patients: an 8-week randomized clinical trial. Int J Food Sci Nutr 60:618–626 (2009).PubMedCrossRefGoogle Scholar
  187. 187.
    Chang, W. C. et al. Beneficial effects of soluble dietary Jerusalem artichoke (Helianthus tuberosus) in the prevention of the onset of type 2 diabetes and non-alcoholic fatty liver disease in high-fructose diet-fed rats. Br J Nutr 112:709–717 (2014).PubMedCrossRefGoogle Scholar
  188. 188.
    Wilcox, G. Insulin and insulin resistance. Clin Biochem Rev 26:19–39 (2005).PubMedPubMedCentralGoogle Scholar
  189. 189.
    Zhen, Z. et al. Anti-diabetic effects of a Coptis chinensis containing new traditional Chinese medicine formula in type 2 diabetic rats. Am J Chin Med 39:53–63 (2011).PubMedCrossRefGoogle Scholar
  190. 190.
    Agyemang, K. et al. Recent Advances in Astragalus membranaceus Anti-Diabetic Research: Pharmacological Effects of Its Phytochemical Constituents. eCAM 2013:654643 (2013).PubMedPubMedCentralGoogle Scholar
  191. 191.
    Jiang, S. et al. Effects of compound K on hyperglycemia and insulin resistance in rats with type 2 diabetes mellitus. Fitoterapia 95:58–64 (2014).PubMedCrossRefGoogle Scholar
  192. 192.
    Wei, S. et al. Ginsenoside Compound K suppresses the hepatic gluconeogenesis via activating adenosine-5’monophosphate kinase: A study in vitro and in vivo. Life Sci 139:8–15 (2015).PubMedCrossRefGoogle Scholar
  193. 193.
    Attele, A. S. et al. Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component. Diabetes 51:1851–1858 (2002).PubMedCrossRefGoogle Scholar
  194. 194.
    Sil, R., Ray, D. & Chakraborti, A. S. Glycyrrhizin ameliorates insulin resistance, hyperglycemia, dyslipidemia and oxidative stress in fructose-induced metabolic syndrome-X in rat model. Indian J Exp Biol 51:129–138 (2013).PubMedGoogle Scholar
  195. 195.
    Sen, S., Roy, M. & Chakraborti, A. S. Ameliorative effects of glycyrrhizin on streptozotocin-induced diabetes in rats. J Pharm Pharmacol 63:287–296 (2011).PubMedCrossRefGoogle Scholar
  196. 196.
    Teng, H. & Choi, Y. H. Optimization of ultrasonicassisted extraction of bioactive alkaloid compounds from rhizoma coptidis (Coptis chinensis Franch.) using response surface methodology. Food Chem 142:299–305 (2014).PubMedCrossRefGoogle Scholar
  197. 197.
    Yang, T. C. et al. Alkaloids from Coptis chinensis root promote glucose uptake in C2C12 myotubes. Fitoterapia 93:239–244 (2014).PubMedCrossRefGoogle Scholar
  198. 198.
    Yang, F., Zhang, T., Zhang, R. & Ito, Y. Application of analytical and preparative high-speed counter-current chromatography for separation of alkaloids from Coptis chinensis Franch. J Chromatogr A 829:137–141 (1998).PubMedCrossRefGoogle Scholar
  199. 199.
    Grahame Hardie, D. Regulation of AMP-activated protein kinase by natural and synthetic activators. Acta Pharmaceutica Sinica. B 6:1–19 (2016).PubMedCrossRefGoogle Scholar
  200. 200.
    Gannon, N. P., Lambalot, E. L. & Vaughan, R. A. The effects of capsaicin and capsaicinoid analogs on metabolic molecular targets in highly energetic tissues and cell types. BioFactors (Oxford, England) 42:229–246 (2016).Google Scholar
  201. 201.
    Seufert, J. SGLT2 inhibitors-an insulin-independent therapeutic approach for treatment of type 2 diabetes: focus on canagliflozin. Diabetes Metab Syndr Obes 8:543 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  202. 202.
    Ehrenkranz, J. R., Lewis, N. G., Kahn, C. R. & Roth, J. Phlorizin: a review. Diabetes/Metabolism Research and Reviews 21:31–38 (2005).PubMedCrossRefGoogle Scholar
  203. 203.
    Nauck, M. A. Update on developments with SGLT2 inhibitors in the management of type 2 diabetes. Drug Des Devel Ther 8:1335–1380 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  204. 204.
    NAGAI, M., KUBO, M., FUJITA, M., INOUE, T. & MATSUO, M. Studies on the constituents of aceraceae plants. II. Structure of aceroside I, a glucoside of a novel cyclic diarylheptanoid from Acer nikoense Maxim. Chem Pharm Bull 26:2805–2810 (1978).CrossRefGoogle Scholar
  205. 205.
    Qu, Y. et al. Antidiabetic effect of Schisandrae Chinensis Fructus involves inhibition of the sodium glucose cotransporter. Drug Dev Res 76:1–8 (2015).PubMedCrossRefGoogle Scholar
  206. 206.
    Yang, J. et al. Sodium-glucose-linked transporter 2 inhibitors from Sophora flavescens. Med Chem Res 24:1265–1271 (2015).CrossRefGoogle Scholar
  207. 207.
    He, X., Fang, J., Huang, L., Wang, J. & Huang, X. Sophora flavescens Ait.: Traditional usage, phytochemistry and pharmacology of an important traditional Chinese medicine. Journal of Ethnopharmacology 172:10–29 (2015).PubMedCrossRefGoogle Scholar
  208. 208.
    Tadera, K., Minami, Y., Takamatsu, K. & Matsuoka, T. Inhibition of α-glucosidase and α-amylase by flavonoids. J Nutr Sci Bitaminol 52:149–153 (2006).CrossRefGoogle Scholar
  209. 209.
    Shobana, S., Sreerama, Y. & Malleshi, N. Composition and enzyme inhibitory properties of finger millet (Eleusine coracana L.) seed coat phenolics: Mode of inhibition of α-glucosidase and pancreatic amylase. Food Chemistry 115:1268–1273 (2009).CrossRefGoogle Scholar
  210. 210.
    Tundis, R., Loizzo, M. & Menichini, F. Natural products as α-amylase and α-glucosidase inhibitors and their hypoglycaemic potential in the treatment of diabetes: an update. Mini Rev Med Chem 10:315–331 (2010).PubMedCrossRefGoogle Scholar
  211. 211.
    Benalla, W., Bellahcen, S. & Bnouham, M. Antidiabetic medicinal plants as a source of alpha glucosidase inhibitors. Curr Diabetes Rev 6:247–254 (2010).PubMedCrossRefGoogle Scholar
  212. 212.
    Poovitha, S. & Parani, M. In vitro and in vivo alpha-amylase and alpha-glucosidase inhibiting activities of the protein extracts from two varieties of bitter gourd (Momordica charantia L.). BMC Complement Altern Med 16 Suppl 1:185 (2016).PubMedPubMedCentralCrossRefGoogle Scholar
  213. 213.
    Heo, S.-J. et al. Diphlorethohydroxycarmalol isolated from Ishige okamurae, a brown algae, a potent α-glucosidase and α-amylase inhibitor, alleviates post-prandial hyperglycemia in diabetic mice. Eur Heart J Cardiovasc Pharmacother 615:252–256 (2009).Google Scholar
  214. 214.
    Bhandari, M. R., Jong-Anurakkun, N., Hong, G. & Kawabata, J. α-Glucosidase and α-amylase inhibitory activities of Nepalese medicinal herb Pakhanbhed (Bergenia ciliata, Haw.). Food Chemistry 106:247–252 (2008).CrossRefGoogle Scholar
  215. 215.
    Lee, S.-H. et al. Dieckol isolated from Ecklonia cava inhibits α-glucosidase and α-amylase in vitro and alleviates postprandial hyperglycemia in streptozotocin-induced diabetic mice. Food Chem Toxicol 48:2633–2637 (2010).PubMedCrossRefGoogle Scholar
  216. 216.
    Kaur, P., Garg, V., Gulati, M. & Singh, S. K. Oral Delivery of Antidiabetic Polypeptide-k: Journey so far and the Road Ahead. Curr Drug Deliv 13:236–244 (2016).PubMedCrossRefGoogle Scholar
  217. 217.
    Ahmad, Z. et al. In vitro anti-diabetic activities and chemical analysis of polypeptide-k and oil isolated from seeds of Momordica charantia (bitter gourd). Molecules 17:9631–9640 (2012).PubMedCrossRefGoogle Scholar
  218. 218.
    Xu, D. et al. Inhibitory activities of caffeoylquinic acid derivatives from Ilex kudingcha C.J. Tseng on alpha-glucosidase from Saccharomyces cerevisiae. J Agric Food Chem 63:3694–3703 (2015).PubMedCrossRefGoogle Scholar
  219. 219.
    Ishikawa, A. et al. Characterization of inhibitors of postprandial hyperglycemia from the leaves of Nerium indicum. J Nutr Sci Vitaminol (Tokyo) 53:166–173 (2007).CrossRefGoogle Scholar
  220. 220.
    Esatbeyoglu, T. et al. Fractionation of Plant Bioactives from Black Carrots (Daucus carota subspecies sativus varietas atrorubens Alef.) by Adsorptive Membrane Chromatography and Analysis of Their Potential Anti-Diabetic Activity. J Agric Food Chem 64:5901–5908 (2016).PubMedCrossRefGoogle Scholar
  221. 221.
    Kwon, Y.-I. I., Vattem, D. A. & Shetty, K. Evaluation of clonal herbs of Lamiaceae species for management of diabetes and hypertension. Asia Pac J Clin Nutr 15:107–118 (2006).PubMedGoogle Scholar
  222. 222.
    Ademiluyi, A. O. & Oboh, G. Soybean phenolic-rich extracts inhibit key-enzymes linked to type 2 diabetes (α-amylase and α-glucosidase) and hypertension (angiotensin I converting enzyme) in vitro. Exp Toxicol Pathol 65:305–309 (2013).PubMedCrossRefGoogle Scholar
  223. 223.
    Striegel, L., Kang, B., Pilkenton, S. J., Rychlik, M. & Apostolidis, E. Effect of black tea and black tea pomace polyphenols on α-glucosidase and α-amylase inhibition, relevant to type 2 diabetes prevention. Front Nutr 2:3 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  224. 224.
    Sun, L., Warren, F. J., Netzel, G. & Gidley, M. J. 3 or 3’-Galloyl substitution plays an important role in association of catechins and theaflavins with porcine pancreatic α-amylase: The kinetics of inhibition of α-amylase by tea polyphenols. J Funct Foods 26:144–156 (2016).CrossRefGoogle Scholar
  225. 225.
    Devi, P. B., Vijayabharathi, R., Sathyabama, S., Malleshi, N. G. & Priyadarisini, V. B. Health benefits of finger millet (Eleusine coracana L.) polyphenols and dietary fiber: a review. J Food Sci Technol 51:1021–1040 (2014).PubMedCrossRefGoogle Scholar
  226. 226.
    Toft-Nielsen, M.-B., Madsbad, S. & Holst, J. J. Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients. Diabetes Care 22:1137–1143 (1999).PubMedCrossRefGoogle Scholar
  227. 227.
    Van Can, J. et al. Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults. Int J Obes 38:784–793 (2014).CrossRefGoogle Scholar
  228. 228.
    Ríos, J. L., Francini, F. & Schinella, G. R. Natural products for the treatment of type 2 diabetes mellitus. Planta Medica 81:975–994 (2015).PubMedCrossRefGoogle Scholar
  229. 229.
    Alam, F., Islam, M. A., Kamal, M. A. & Gan, S. H. Updates on managing type 2 diabetes mellitus with natural products: towards antidiabetic drug development. Curr Med Chem 23:1–37 (2016).CrossRefGoogle Scholar

Copyright information

© The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  1. 1.College of Korean MedicineKyung Hee UniversitySeoulRepublic of Korea
  2. 2.Department of Science in Korean Medicine, Graduate SchoolKyung Hee UniversitySeoulRepublic of Korea

Personalised recommendations