Herbal Medicine in Diabetes Mellitus with Cardiovascular Diseases

  • Salih Tunc Kaya
  • Celal Guven
  • Eylem Taskin


Diabetic patients are more susceptible to cardiovascular diseases than nondiabetic patients. In addition, cardiovascular diseases associated with diabetes are a major cause of mortality and morbidity among diabetic people in the world. Diabetes has alarmingly continued to affect human beings around the world, and still continues especially in developed or developing countries with an increasing pace. There is a growing need for innovative and effective therapies for the management of hyperglycemia and the improvement of cardiovascular complications in diabetic patients as well. Herein, herbal medicine or products play an essential role in developing a new cure or improving the efficiency of the antidiabetic drugs with the features of cardioprotective effects. This chapter highlights some promising herbal remedies, including resveratrol, berberine, ginseng, curcumin, and ginkgo in the therapeutic usage for controlling of hyperglycemia as well as in either preventing or decreasing the susceptibility of diabetic patients to cardiovascular diseases with a focus on possible underlying mechanisms of their effects.


Herbal products Diabetes Mellitus Cardiovascular diseases MicroRNAs 


  1. Abdel Aziz MT, El-Asmar MF, El-Ibrashy IN, Rezq AM, Al-Malki AL, Wassef MA, Fouad HH, Ahmed HH, Taha FM, Hassouna AA, Morsi HM (2012) Effect of novel water soluble curcumin derivative on experimental type-1 diabetes mellitus (short term study). Diabetol Metab Syndr 4:30PubMedPubMedCentralCrossRefGoogle Scholar
  2. Abo-Salem OM, Harisa GI, Ali TM, El-Sayed El SM, Abou-Elnour FM (2014) Curcumin ameliorates streptozotocin-induced heart injury in rats. J Biochem Mol Toxicol 28:263–270PubMedCrossRefGoogle Scholar
  3. American Diabetes Association (2010) Diagnosis and classification of diabetes mellitus. Diabetes Care 33(Suppl 1):S62–S69PubMedCentralCrossRefPubMedGoogle Scholar
  4. Amin KA, Awad EM, Nagy MA (2011) Effects of Panax quinquefolium on streptozotocin-induced diabetic rats: role of C-peptide, nitric oxide and oxidative stress. Int J Clin Exp Med 4:136–147PubMedPubMedCentralGoogle Scholar
  5. Anupunpisit V, Petpiboolthai H, Khimmaktong W (2015) Microvasculature improvement of heart in diabetic rat with curcumin supplementation. J Med Assoc Thail 98(Suppl 10):S74–S83Google Scholar
  6. Ar’rajab A, Ahren B (1993) Long-term diabetogenic effect of streptozotocin in rats. Pancreas 8:50–57PubMedCrossRefGoogle Scholar
  7. Ates O, Cayli SR, Yucel N, Altinoz E, Kocak A, Durak MA, Turkoz Y, Yologlu S (2007) Central nervous system protection by resveratrol in streptozotocin-induced diabetic rats. J Clin Neurosci 14:256–260PubMedCrossRefGoogle Scholar
  8. Atkinson MA, Eisenbarth GS, Michels AW (2014) Type 1 diabetes. Lancet 383:69–82PubMedCrossRefGoogle Scholar
  9. Aziz MT, El Ibrashy IN, Mikhailidis DP, Rezq AM, Wassef MA, Fouad HH, Ahmed HH, Sabry DA, Shawky HM, Hussein RE (2013) Signaling mechanisms of a water soluble curcumin derivative in experimental type 1 diabetes with cardiomyopathy. Diabetol Metab Syndr 5:13PubMedPubMedCentralCrossRefGoogle Scholar
  10. Aziz MT, El-Asmar MF, Rezq AM, Wassef MA, Fouad H, Roshdy NK, Ahmed HH, Rashed LA, Sabry D, Taha FM, Hassouna A (2014) Effects of a novel curcumin derivative on insulin synthesis and secretion in streptozotocin-treated rat pancreatic islets in vitro. Chin Med 9:3PubMedPubMedCentralCrossRefGoogle Scholar
  11. Baeg IH, So SH (2013) The world ginseng market and the ginseng (Korea). J Ginseng Res 37:1–7PubMedPubMedCentralCrossRefGoogle Scholar
  12. Bagul PK, Dinda AK, Banerjee SK (2015) Effect of resveratrol on sirtuins expression and cardiac complications in diabetes. Biochem Biophys Res Commun 468:221–227PubMedCrossRefGoogle Scholar
  13. Balakumar P, Sharma NK (2012) Healing the diabetic heart: does myocardial preconditioning work? Cell Signal 24:53–59PubMedCrossRefGoogle Scholar
  14. Balakumar P, Maung UK, Jagadeesh G (2016) Prevalence and prevention of cardiovascular disease and diabetes mellitus. Pharmacol Res 113:600–609PubMedCrossRefGoogle Scholar
  15. Bhatt LK, Veeranjaneyulu A (2014) Enhancement of matrix metalloproteinase 2 and 9 inhibitory action of minocycline by aspirin: an approach to attenuate outcome of acute myocardial infarction in diabetes. Arch Med Res 45:203–209PubMedCrossRefGoogle Scholar
  16. Bhatt JK, Thomas S, Nanjan MJ (2012) Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutr Res 32:537–541PubMedCrossRefGoogle Scholar
  17. Blade C, Baselga-Escudero L, Arola-Arnal A (2014) microRNAs as new targets of dietary polyphenols. Curr Pharm Biotechnol 15:343–351PubMedCrossRefGoogle Scholar
  18. Bo S, Ponzo V, Ciccone G, Evangelista A, Saba F, Goitre I, Procopio M, Pagano GF, Cassader M, Gambino R (2016) Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial. Pharmacol Res 111:896–905PubMedCrossRefGoogle Scholar
  19. Bonnefont-Rousselot D (2016) Resveratrol and cardiovascular diseases. Nutrients 8. PubMedCentralCrossRefPubMedGoogle Scholar
  20. Brasnyo P, Molnar GA, Mohas M, Marko L, Laczy B, Cseh J, Mikolas E, Szijarto IA, Merei A, Halmai R, Meszaros LG, Sumegi B, Wittmann I (2011) Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br J Nutr 106:383–389PubMedCrossRefGoogle Scholar
  21. Brindisi MC, Bouillet B, Verges B, Halimi S (2010) Cardiovascular complications in type 1 diabetes mellitus. Diabetes Metab 36:341–344PubMedCrossRefGoogle Scholar
  22. Carolo Dos Santos K, Pereira Braga C, Octavio Barbanera P, Seiva FR, Fernandes Junior A, Fernandes AA (2014) Cardiac energy metabolism and oxidative stress biomarkers in diabetic rat treated with resveratrol. PLoS One 9:e102775PubMedPubMedCentralCrossRefGoogle Scholar
  23. Chan LS, Yue PY, Mak NK, Wong RN (2009) Role of microRNA-214 in ginsenoside-Rg1-induced angiogenesis. Eur J Pharm Sci 38:370–377PubMedCrossRefGoogle Scholar
  24. Chang W (2017) Non-coding RNAs and berberine: a new mechanism of its anti-diabetic activities. Eur J Pharmacol 795:8–12PubMedCrossRefGoogle Scholar
  25. Chang W, Zhang M, Meng Z, Yu Y, Yao F, Hatch GM, Chen L (2015) Berberine treatment prevents cardiac dysfunction and remodeling through activation of 5′-adenosine monophosphate-activated protein kinase in type 2 diabetic rats and in palmitate-induced hypertrophic H9c2 cells. Eur J Pharmacol 769:55–63PubMedCrossRefGoogle Scholar
  26. Chang W, Li K, Guan F, Yao F, Yu Y, Zhang M, Hatch GM, Chen L (2016) Berberine pretreatment confers cardioprotection against ischemia-reperfusion injury in a rat model of type 2 diabetes. J Cardiovasc Pharmacol Ther 21:486–494PubMedCrossRefGoogle Scholar
  27. Chen ZC, Cheng YZ, Chen LJ, Cheng KC, Li Y, Cheng J (2012) Increase of ATP-sensitive potassium (K(ATP)) channels in the heart of type-1 diabetic rats. Cardiovasc Diabetol 11:8PubMedPubMedCentralCrossRefGoogle Scholar
  28. Chen K, Li G, Geng F, Zhang Z, Li J, Yang M, Dong L, Gao F (2014) Berberine reduces ischemia/reperfusion-induced myocardial apoptosis via activating AMPK and PI3K-Akt signaling in diabetic rats. Apoptosis 19:946–957PubMedCrossRefGoogle Scholar
  29. Chen R, Peng X, Du W, Wu Y, Huang B, Xue L, Wu Q, Qiu H, Jiang Q (2015) Curcumin attenuates cardiomyocyte hypertrophy induced by high glucose and insulin via the PPAR-gamma/Akt/NO signaling pathway. Diabetes Res Clin Pract 108:235–242PubMedCrossRefGoogle Scholar
  30. Cheng D, Liang B, Li Y (2013) Antihyperglycemic effect of Ginkgo biloba extract in streptozotocin-induced diabetes in rats. Biomed Res Int 2013:162724PubMedGoogle Scholar
  31. Chi TC, Chen WP, Chi TL, Kuo TF, Lee SS, Cheng JT, Su MJ (2007) Phosphatidylinositol-3-kinase is involved in the antihyperglycemic effect induced by resveratrol in streptozotocin-induced diabetic rats. Life Sci 80:1713–1720CrossRefGoogle Scholar
  32. Chueh WH, Lin JY (2011) Berberine, an isoquinoline alkaloid in herbal plants, protects pancreatic islets and serum lipids in nonobese diabetic mice. J Agric Food Chem 59:8021–8027PubMedCrossRefGoogle Scholar
  33. Chueh WH, Lin JY (2012a) Berberine, an isoquinoline alkaloid, inhibits streptozotocin-induced apoptosis in mouse pancreatic islets through down-regulating Bax/Bcl-2 gene expression ratio. Food Chem 132:252–260PubMedCrossRefGoogle Scholar
  34. Chueh WH, Lin JY (2012b) Protective effect of berberine on serum glucose levels in non-obese diabetic mice. Int Immunopharmacol 12:534–538PubMedCrossRefGoogle Scholar
  35. Chuengsamarn S, Rattanamongkolgul S, Luechapudiporn R, Phisalaphong C, Jirawatnotai S (2012) Curcumin extract for prevention of type 2 diabetes. Diabetes Care 35:2121–2127PubMedPubMedCentralCrossRefGoogle Scholar
  36. Costantino S, Paneni F, Luscher TF, Cosentino F (2016) MicroRNA profiling unveils hyperglycaemic memory in the diabetic heart. Eur Heart J 37:572–576PubMedCrossRefGoogle Scholar
  37. Dai P, Wang J, Lin L, Zhang Y, Wang Z (2015) Renoprotective effects of berberine as adjuvant therapy for hypertensive patients with type 2 diabetes mellitus: evaluation via biochemical markers and color Doppler ultrasonography. Exp Ther Med 10:869–876PubMedPubMedCentralCrossRefGoogle Scholar
  38. Dai D, Zhang CF, Williams S, Yuan CS, Wang CZ (2017) Ginseng on cancer: potential role in modulating inflammation-mediated angiogenesis. Am J Chin Med 45:13–22PubMedCrossRefGoogle Scholar
  39. Defeudis FV (2003) A brief history of EGb 761 and its therapeutic uses. Pharmacopsychiatry 36(Suppl 1):S2–S7PubMedGoogle Scholar
  40. Dong SF, Hong Y, Liu M, Hao YZ, Yu HS, Liu Y, Sun JN (2011) Berberine attenuates cardiac dysfunction in hyperglycemic and hypercholesterolemic rats. Eur J Pharmacol 660:368–374PubMedCrossRefGoogle Scholar
  41. Dong H, Wang N, Zhao L, Lu F (2012) Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis. Evid Based Complement Alternat Med 2012:591654PubMedPubMedCentralCrossRefGoogle Scholar
  42. Dziwenka M, Coppock RW (2016) Ginkgo biloba. In: Nutraceuticals: efficacy, safety and toxicity. Elsevier, Amsterdam, pp 681–691CrossRefGoogle Scholar
  43. El-Bahr SM (2013) Curcumin regulates gene expression of insulin like growth factor, B-cell CLL/lymphoma 2 and antioxidant enzymes in streptozotocin induced diabetic rats. BMC Complement Altern Med 13:368PubMedPubMedCentralCrossRefGoogle Scholar
  44. El-Moselhy MA, Taye A, Sharkawi SS, El-Sisi SF, Ahmed AF (2011) The antihyperglycemic effect of curcumin in high fat diet fed rats. Role of TNF-alpha and free fatty acids. Food Chem Toxicol 49:1129–1140PubMedCrossRefGoogle Scholar
  45. Fan Y, Liu L, Fang K, Huang T, Wan L, Liu Y, Zhang S, Yan D, Li G, Gao Y, Lv Y, Chen Y, Tu Y (2016) Resveratrol ameliorates cardiac hypertrophy by Down-regulation of miR-155 through activation of breast cancer type 1 susceptibility protein. J Am Heart Assoc 5:e002648PubMedPubMedCentralGoogle Scholar
  46. Fancher IS, Dick GM, Hollander JM (2013) Diabetes mellitus reduces the function and expression of ATP-dependent K(+) channels in cardiac mitochondria. Life Sci 92:664–668PubMedCrossRefGoogle Scholar
  47. Fitzl G, Welt K, Martin R, Dettmer D, Hermsdorf T, Clemens N, Konig S (2000) The influence of hypoxia on the myocardium of experimentally diabetic rats with and without protection by Ginkgo biloba extract I. Ultrastructural and biochemical investigations on cardiomyocytes. Exp Toxicol Pathol 52:419–430PubMedCrossRefGoogle Scholar
  48. Forbes JM, Cooper ME (2013) Mechanisms of diabetic complications. Physiol Rev 93:137–188PubMedCrossRefGoogle Scholar
  49. Frendo-Cumbo S, Macpherson RE, Wright DC (2016) Beneficial effects of combined resveratrol and metformin therapy in treating diet-induced insulin resistance. Physiol Rep 4:e12877PubMedPubMedCentralCrossRefGoogle Scholar
  50. Gao Y, Kang L, Li C, Wang X, Sun C, Li Q, Liu R, Wang J (2016) Resveratrol ameliorates diabetes-induced cardiac dysfunction through AT1R-ERK/p38 MAPK signaling pathway. Cardiovasc Toxicol 16:130–137PubMedCrossRefGoogle Scholar
  51. Gencoglu H, Tuzcu M, Hayirli A, Sahin K (2015) Protective effects of resveratrol against streptozotocin-induced diabetes in rats by modulation of visfatin/sirtuin-1 pathway and glucose transporters. Int J Food Sci Nutr 66:314–320PubMedCrossRefGoogle Scholar
  52. Gilmartin AB, Ural SH, Repke JT (2008) Gestational diabetes mellitus. Rev Obstet Gynecol 1:129–134PubMedGoogle Scholar
  53. Gu Y, Zhang Y, Shi X, Li X, Hong J, Chen J, Gu W, Lu X, Xu G, Ning G (2010) Effect of traditional Chinese medicine berberine on type 2 diabetes based on comprehensive metabonomics. Talanta 81:766–772PubMedCrossRefGoogle Scholar
  54. Gui QF, Xu ZR, Xu KY, Yang YM (2016a) The efficacy of ginseng-related therapies in type 2 diabetes mellitus. Medicine (United States) 95:e2584Google Scholar
  55. Gui QF, Xu ZR, Xu KY, Yang YM (2016b) The efficacy of ginseng-related therapies in type 2 diabetes mellitus: an updated systematic review and meta-analysis. Medicine (Baltimore) 95:e2584CrossRefGoogle Scholar
  56. Guo S, Yao Q, Ke Z, Chen H, Wu J, Liu C (2015) Resveratrol attenuates high glucose-induced oxidative stress and cardiomyocyte apoptosis through AMPK. Mol Cell Endocrinol 412:85–94PubMedCrossRefGoogle Scholar
  57. Gupta SC, Patchva S, Koh W, Aggarwal BB (2012) Discovery of curcumin, a component of golden spice, and its miraculous biological activities. Clin Exp Pharmacol Physiol 39:283–299PubMedPubMedCentralCrossRefGoogle Scholar
  58. Hayat SA, Patel B, Khattar RS, Malik RA (2004) Diabetic cardiomyopathy: mechanisms, diagnosis and treatment. Clin Sci (Lond) 107:539–557CrossRefGoogle Scholar
  59. Hosseini SA, Alipour M, Ghadiry A, Zakerkish M (2016) The effects of standardized extract of ginseng (G115) on blood sugar control and inflammatory factors in patients with type 2 diabetes: a double-blind clinical trial. Int J Pharm Res Allied Sci 5:55–59Google Scholar
  60. Howell JC, Chun E, Farrell AN, Hur EY, Caroti CM, Iuvone PM, Haque R (2013) Global microRNA expression profiling: curcumin (diferuloylmethane) alters oxidative stress-responsive microRNAs in human ARPE-19 cells. Mol Vis 19:544–560PubMedPubMedCentralGoogle Scholar
  61. Huang JP, Huang SS, Deng JY, Chang CC, Day YJ, Hung LM (2010) Insulin and resveratrol act synergistically, preventing cardiac dysfunction in diabetes, but the advantage of resveratrol in diabetics with acute heart attack is antagonized by insulin. Free Radic Biol Med 49:1710–1721PubMedCrossRefGoogle Scholar
  62. IDF (2016) Diabetes and cardiovascular disease. International Diabetes Federation, Brussels, BelgiumGoogle Scholar
  63. Ilyas EI, Nur BM, Laksono SP, Bahtiar A, Estuningtyas A, Vitasyana C, Kusmana D, Suyatna FD, Tadjudin MK, Freisleben HJ (2016) Effects of curcumin on parameters of myocardial oxidative stress and of mitochondrial glutathione turnover in Reoxygenation after 60 minutes of hypoxia in isolated perfused working Guinea pig hearts. Adv Pharmacol Sci 2016:6173648PubMedPubMedCentralGoogle Scholar
  64. Isah T (2015) Rethinking Ginkgo biloba L.: medicinal uses and conservation. Pharmacogn Rev 9:140–148PubMedPubMedCentralCrossRefGoogle Scholar
  65. Jacobs BP, Browner WS (2000) Ginkgo biloba: a living fossil. Am J Med 108:341–342PubMedCrossRefGoogle Scholar
  66. Jin Y, Khadka DB, Cho WJ (2016) Pharmacological effects of berberine and its derivatives: a patent update. Expert Opin Ther Pat 26:229–243PubMedCrossRefGoogle Scholar
  67. Jung CH, Seog HM, Choi IW, Choi HD, Cho HY (2005) Effects of wild ginseng (Panax ginseng C.A. Meyer) leaves on lipid peroxidation levels and antioxidant enzyme activities in streptozotocin diabetic rats. J Ethnopharmacol 98:245–250PubMedCrossRefGoogle Scholar
  68. Karaca T, Yoruk M, Yoruk IH, Uslu S (2010) Effects of extract of green tea and ginseng on pancreatic beta cells and levels of serum glucose, insulin, cholesterol and triglycerides in rats with experimentally streptozotocin-induced diabetes: a histochemical and immunohistochemical study. J Anim Vet Adv 9:102–107CrossRefGoogle Scholar
  69. Karuppagounder V, Arumugam S, Giridharan VV, Sreedhar R, Bose RJ, Vanama J, Palaniyandi SS, Konishi T, Watanabe K, Thandavarayan RA (2017) Tiny molecule, big power: multi-target approach for curcumin in diabetic cardiomyopathy. Nutrition 34:47–54PubMedCrossRefGoogle Scholar
  70. Khamaneh AM, Alipour MR, Sheikhzadeh Hesari F, Ghadiri Soufi F (2015) A signature of microRNA-155 in the pathogenesis of diabetic complications. J Physiol Biochem 71:301–309PubMedCrossRefGoogle Scholar
  71. Kim HY, Kang KS, Yamabe N, Nagai R, Yokozawa T (2007) Protective effect of heat-processed American ginseng against diabetic renal damage in rats. J Agric Food Chem 55:8491–8497PubMedCrossRefGoogle Scholar
  72. Kim YJ, Zhang D, Yang DC (2015) Biosynthesis and biotechnological production of ginsenosides. Biotechnol Adv 33:717–735PubMedCrossRefGoogle Scholar
  73. Kim JH, Pan JH, Cho HT, Kim YJ (2016a) Black ginseng extract counteracts streptozotocin-induced diabetes in mice. PLoS One 11:e0146843PubMedPubMedCentralCrossRefGoogle Scholar
  74. Kim JS, Jang HJ, Kim SS, Oh MY, Kim HJ, Lee SY, Eom DW, Ham JY, Han DJ (2016b) Red ginseng administration before islet isolation attenuates apoptosis and improves islet function and transplant outcome in a syngeneic mouse marginal islet mass model. Transplant Proc 48:1258–1265PubMedCrossRefGoogle Scholar
  75. King AJ (2012) The use of animal models in diabetes research. Br J Pharmacol 166:877–894PubMedPubMedCentralCrossRefGoogle Scholar
  76. Kong WJ, Zhang H, Song DQ, Xue R, Zhao W, Wei J, Wang YM, Shan N, Zhou ZX, Yang P, You XF, Li ZR, Si SY, Zhao LX, Pan HN, Jiang JD (2009) Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. Metabolism 58:109–119PubMedCrossRefGoogle Scholar
  77. Kronski E, Fiori ME, Barbieri O, Astigiano S, Mirisola V, Killian PH, Bruno A, Pagani A, Rovera F, Pfeffer U, Sommerhoff CP, Noonan DM, Nerlich AG, Fontana L, Bachmeier BE (2014) MiR181b is induced by the chemopreventive polyphenol curcumin and inhibits breast cancer metastasis via down-regulation of the inflammatory cytokines CXCL1 and -2. Mol Oncol 8:581–595PubMedPubMedCentralCrossRefGoogle Scholar
  78. Ku CR, Lee HJ, Kim SK, Lee EY, Lee MK, Lee EJ (2012) Resveratrol prevents streptozotocin-induced diabetes by inhibiting the apoptosis of pancreatic beta-cell and the cleavage of poly (ADP-ribose) polymerase. Endocr J 59:103–109PubMedCrossRefGoogle Scholar
  79. Kudolo GB, Wang W, Elrod R, Barrientos J, Haase A, Blodgett J (2006a) Short-term ingestion of Ginkgo biloba extract does not alter whole body insulin sensitivity in non-diabetic, pre-diabetic or type 2 diabetic subjects – a randomized double-blind placebo-controlled crossover study. Clin Nutr 25:123–134PubMedCrossRefGoogle Scholar
  80. Kudolo GB, Wang W, Javors M, Blodgett J (2006b) The effect of the ingestion of Ginkgo biloba extract (EGb 761) on the pharmacokinetics of metformin in non-diabetic and type 2 diabetic subjects – a double blind placebo-controlled, crossover study. Clin Nutr 25:606–616PubMedCrossRefGoogle Scholar
  81. Kumar S, Singh R, Vasudeva N, Sharma S (2012) Acute and chronic animal models for the evaluation of anti-diabetic agents. Cardiovasc Diabetol 11:9PubMedPubMedCentralCrossRefGoogle Scholar
  82. Kumar A, Ekavali CK, Mukherjee M, Pottabathini R, Dhull DK (2015) Current knowledge and pharmacological profile of berberine: an update. Eur J Pharmacol 761:288–297PubMedCrossRefGoogle Scholar
  83. Lan J, Zhao Y, Dong F, Yan Z, Zheng W, Fan J, Sun G (2015) Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol 161:69–81PubMedCrossRefGoogle Scholar
  84. Lee CH, Kim JH (2014) A review on the medicinal potentials of ginseng and ginsenosides on cardiovascular diseases. J Ginseng Res 38:161–166PubMedPubMedCentralCrossRefGoogle Scholar
  85. Li KK, Gong XJ (2015) A review on the medicinal potential of Panax ginseng saponins in diabetes mellitus. RSC Adv 5:47353–47366CrossRefGoogle Scholar
  86. Li J, Wang P, Zhu Y, Chen Z, Shi T, Lei W, Yu S (2015) Curcumin inhibits neuronal loss in the retina and elevates Ca(2)(+)/calmodulin-dependent protein kinase II activity in diabetic rats. J Ocul Pharmacol Ther 31:555–562PubMedPubMedCentralCrossRefGoogle Scholar
  87. Lim S, Yoon JW, Kang SM, Choi SH, Cho BJ, Kim M, Park HS, Cho HJ, Shin H, Kim YB, Kim HS, Jang HC, Park KS (2011) EGb761, a Ginkgo biloba extract, is effective against atherosclerosis in vitro, and in a rat model of type 2 diabetes. PLoS One 6:e20301PubMedPubMedCentralCrossRefGoogle Scholar
  88. Liu Z, Wang LJ, Li X, Hu JN, Chen Y, Ruan CC, Sun GZ (2009) Hypoglycemic effects of malonyl-ginsenosides extracted from roots of Panax ginseng on streptozotocin-induced diabetic mice. Phytother Res 23:1426–1430PubMedCrossRefGoogle Scholar
  89. Lu Q, Zuo WZ, Ji XJ, Zhou YX, Liu YQ, Yao XQ, Zhou XY, Liu YW, Zhang F, Yin XX (2015) Ethanolic Ginkgo biloba leaf extract prevents renal fibrosis through Akt/mTOR signaling in diabetic nephropathy. Phytomedicine 22:1071–1078PubMedCrossRefGoogle Scholar
  90. Ma W, Li J, Hu J, Cheng Y, Wang J, Zhang X, Xu M (2016) miR214-regulated p53-NOX4/p66shc pathway plays a crucial role in the protective effect of Ginkgolide B against cisplatin-induced cytotoxicity in HEI-OC1 cells. Chem Biol Interact 245:72–81PubMedCrossRefGoogle Scholar
  91. Majithiya JB, Balaraman R (2005) Time-dependent changes in antioxidant enzymes and vascular reactivity of aorta in streptozotocin-induced diabetic rats treated with curcumin. J Cardiovasc Pharmacol 46:697–705PubMedCrossRefGoogle Scholar
  92. Mccowen KC, Smith RJ (2013) Diabetes mellitus: classification and chemical pathology A2 - caballero, Benjamin. Encyclopedia of human nutrition, 3rd edn. Academic Press, Waltham, pp 17–24Google Scholar
  93. Meghana K, Sanjeev G, Ramesh B (2007) Curcumin prevents streptozotocin-induced islet damage by scavenging free radicals: a prophylactic and protective role. Eur J Pharmacol 577:183–191PubMedPubMedCentralCrossRefGoogle Scholar
  94. Mohammadi A, Mansoori B, Baradaran B (2017) Regulation of miRNAs by herbal medicine: an emerging field in cancer therapies. Biomed Pharmacother 86:262–270PubMedCrossRefGoogle Scholar
  95. Momtazi AA, Shahabipour F, Khatibi S, Johnston TP, Pirro M, Sahebkar A (2016) Curcumin as a MicroRNA regulator in cancer: a review. Rev Physiol Biochem Pharmacol 171:1–38PubMedCrossRefGoogle Scholar
  96. Monami M, Luzzi C, Lamanna C, Chiasserini V, Addante F, Desideri CM, Masotti G, Marchionni N, Mannucci E (2006) Three-year mortality in diabetic patients treated with different combinations of insulin secretagogues and metformin. Diabetes Metab Res Rev 22:477–482PubMedCrossRefGoogle Scholar
  97. Monami M, Dicembrini I, Mannucci E (2014) Dipeptidyl peptidase-4 inhibitors and heart failure: a meta-analysis of randomized clinical trials. Nutr Metab Cardiovasc Dis 24:689–697PubMedCrossRefGoogle Scholar
  98. Moon HK, Kim KS, Chung SK, Kim JK (2015) Effect of wild Korean ginseng (Panax ginseng) extract on blood glucose and serum lipid contents in rats with multiple low-dose streptozotocin-induced diabetes. Food Sci Biotechnol 24:1505–1511CrossRefGoogle Scholar
  99. Movahed A, Nabipour I, Lieben Louis X, Thandapilly SJ, Yu L, Kalantarhormozi M, Rekabpour SJ, Netticadan T (2013) Antihyperglycemic effects of short term resveratrol supplementation in type 2 diabetic patients. Evid Based Complement Alternat Med 2013:851267PubMedPubMedCentralCrossRefGoogle Scholar
  100. Mukhopadhyay P, Pacher P, Das DK (2011) MicroRNA signatures of resveratrol in the ischemic heart. Ann N Y Acad Sci 1215:109–116PubMedPubMedCentralCrossRefGoogle Scholar
  101. Nakou ES, Mavrakis H, Vardas PE (2012) Are diabetic patients at increased risk of arrhythmias? Hell J Cardiol 53:335–339Google Scholar
  102. Naseem M, Zaman MQ, Nazih H, Ouguerram K, Rabbani I, Zaneb H, Yaqoob T, Rehman HU, Michel J, Tahir SK, Yousaf MS, Majeed KA, Hussain MS (2016) The effects of Ginkgo Biloba leaf extract on metabolic disturbances associated to alloxan-induced diabetic rats. J Anim Plant Sci 26:627–635Google Scholar
  103. Neerati P, Devde R, Gangi AK (2014) Evaluation of the effect of curcumin capsules on glyburide therapy in patients with type-2 diabetes mellitus. Phytother Res 28:1796–1800PubMedCrossRefGoogle Scholar
  104. Oh MJ, Kim HJ, Park EY, Ha NH, Song MG, Choi SH, Chun BG, Kim DH (2017) The effect of Korean red ginseng extract on rosiglitazone-induced improvement of glucose regulation in diet-induced obese mice. J Ginseng Res 41:52–59PubMedCrossRefGoogle Scholar
  105. Palma HE, Wolkmer P, Gallio M, Correa MM, Schmatz R, Thome GR, Pereira LB, Castro VS, Pereira AB, Bueno A, De Oliveira LS, Rosolen D, Mann TR, De Cecco BS, Graca DL, Lopes ST, Mazzanti CM (2014) Oxidative stress parameters in blood, liver, and kidney of diabetic rats treated with curcumin and/or insulin. Mol Cell Biochem 386:199–210PubMedCrossRefGoogle Scholar
  106. Palsamy P, Subramanian S (2008) Resveratrol, a natural phytoalexin, normalizes hyperglycemia in streptozotocin-nicotinamide induced experimental diabetic rats. Biomed Pharmacother 62:598–605PubMedCrossRefGoogle Scholar
  107. Pan ZW, Lu YJ, Yang BF (2010) MicroRNAs: a novel class of potential therapeutic targets for cardiovascular diseases. Acta Pharmacol Sin 31:1–9PubMedCrossRefGoogle Scholar
  108. Pang B, Zhao LH, Zhou Q, Zhao TY, Wang H, Gu CJ, Tong XL (2015a) Application of berberine on treating type 2 diabetes mellitus. Int J Endocrinol 2015:905749PubMedPubMedCentralCrossRefGoogle Scholar
  109. Pang XF, Zhang LH, Bai F, Wang NP, Shah AI, Garner R, Zhao ZQ (2015b) Dual ACE-inhibition and angiotensin II AT(1) receptor antagonism with curcumin attenuate maladaptive cardiac repair and improve ventricular systolic function after myocardial infarction in rat heart. Eur J Pharmacol 746:22–30PubMedCrossRefGoogle Scholar
  110. Park HJ, Kim DH, Park SJ, Kim JM, Ryu JH (2012) Ginseng in traditional herbal prescriptions. J Ginseng Res 36:225–241PubMedPubMedCentralCrossRefGoogle Scholar
  111. Prasad S, Aggarwal BB (2011) Turmeric, the golden spice: from traditional medicine to modern medicine. In: IFF B, Wachtel-Galor S (eds) Herbal medicine: biomolecular and clinical aspects, 2nd edn. CRC Press/Taylor & Francis Llc., Boca Raton (FL), pp 263–288CrossRefGoogle Scholar
  112. Rahimi HR, Mohammadpour AH, Dastani M, Jaafari MR, Abnous K, Ghayour Mobarhan M, Kazemi Oskuee R (2016) The effect of nano-curcumin on HbA1c, fasting blood glucose, and lipid profile in diabetic subjects: a randomized clinical trial. Avicenna J Phytomed 6:567–577PubMedPubMedCentralGoogle Scholar
  113. Rashid K, Sil PC (2015) Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats. Toxicol Appl Pharmacol 282:297–310PubMedCrossRefGoogle Scholar
  114. Rawal S, Manning P, Katare R (2014) Cardiovascular microRNAs: as modulators and diagnostic biomarkers of diabetic heart disease. Cardiovasc Diabetol 13:44PubMedPubMedCentralCrossRefGoogle Scholar
  115. Ren M, Yang S, Li J, Hu Y, Ren Z, Ren S (2013) Ginkgo biloba L. extract enhances the effectiveness of syngeneic bone marrow mesenchymal stem cells in lowering blood glucose levels and reversing oxidative stress. Endocrine 43:360–369PubMedCrossRefGoogle Scholar
  116. Rhee KJ, Lee CG, Kim SW, Gim DH, Kim HC, Jung BD (2015) Extract of Ginkgo Biloba ameliorates streptozotocin-induced type 1 diabetes mellitus and high-fat diet-induced type 2 diabetes mellitus in mice. Int J Med Sci 12:987–994PubMedPubMedCentralCrossRefGoogle Scholar
  117. Saini AS, Taliyan R, Sharma PL (2014) Protective effect and mechanism of Ginkgo biloba extract-EGb 761 on STZ-induced diabetic cardiomyopathy in rats. Pharmacogn Mag 10:172–178PubMedPubMedCentralCrossRefGoogle Scholar
  118. Schmatz R, Schetinger MR, Spanevello RM, Mazzanti CM, Stefanello N, Maldonado PA, Gutierres J, Correa Mde C, Girotto E, Moretto MB, Morsch VM (2009) Effects of resveratrol on nucleotide degrading enzymes in streptozotocin-induced diabetic rats. Life Sci 84:345–350PubMedCrossRefGoogle Scholar
  119. Schmatz R, Perreira LB, Stefanello N, Mazzanti C, Spanevello R, Gutierres J, Bagatini M, Martins CC, Abdalla FH, Daci Da Silva Serres J, Zanini D, Vieira JM, Cardoso AM, Schetinger MR, Morsch VM (2012) Effects of resveratrol on biomarkers of oxidative stress and on the activity of delta aminolevulinic acid dehydratase in liver and kidney of streptozotocin-induced diabetic rats. Biochimie 94:374–383PubMedCrossRefGoogle Scholar
  120. Schneider R, Welt K, Aust W, Kluge R, Loster H, Fitzl G (2010) Cardiovascular autonomic neuropathy in spontaneously diabetic rats with and without application of EGb 761. Histol Histopathol 25:1581–1590PubMedGoogle Scholar
  121. Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, Mcguire DK, Ray KK, Leiter LA, Raz I, SAVOR-TIMI 53 Steering Committee and Investigators (2013) Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 369:1317–1326PubMedCrossRefGoogle Scholar
  122. Sekar D, Venugopal B, Sekar P, Ramalingam K (2016) Role of microRNA 21 in diabetes and associated/related diseases. Gene 582:14–18PubMedCrossRefGoogle Scholar
  123. Sen S, Chen S, Wu Y, Feng B, Lui EK, Chakrabarti S (2013) Preventive effects of north American ginseng (Panax quinquefolius) on diabetic retinopathy and cardiomyopathy. Phytother Res 27:290–298PubMedCrossRefGoogle Scholar
  124. Seo YS, Shon MY, Kong R, Kang OH, Zhou T, Kim DY, Kwon DY (2016) Black ginseng extract exerts anti-hyperglycemic effect via modulation of glucose metabolism in liver and muscle. J Ethnopharmacol 190:231–240PubMedCrossRefGoogle Scholar
  125. Sethupathy P (2016) The promise and challenge of therapeutic MicroRNA silencing in diabetes and metabolic diseases. Curr Diab Rep 16:52PubMedPubMedCentralCrossRefGoogle Scholar
  126. Shakibaei M, Harikumar KB, Aggarwal BB (2009) Resveratrol addiction: to die or not to die. Mol Nutr Food Res 53:115–128PubMedCrossRefGoogle Scholar
  127. Shi Y, Wan X, Shao N, Ye R, Zhang N, Zhang Y (2016) Protective and antiangiopathy effects of ginsenoside re against diabetes mellitus via the activation of p38 MAPK, ERK1/2 and JNK signaling. Mol Med Rep 14:4849–4856PubMedCrossRefGoogle Scholar
  128. Siegel G, Ermilov E, Knes O, Rodriguez M (2014) Combined lowering of low grade systemic inflammation and insulin resistance in metabolic syndrome patients treated with Ginkgo biloba. Atherosclerosis 237:584–588PubMedCrossRefGoogle Scholar
  129. Soetikno V, Sari FR, Sukumaran V, Lakshmanan AP, Mito S, Harima M, Thandavarayan RA, Suzuki K, Nagata M, Takagi R, Watanabe K (2012) Curcumin prevents diabetic cardiomyopathy in streptozotocin-induced diabetic rats: possible involvement of PKC-MAPK signaling pathway. Eur J Pharm Sci 47:604–614PubMedCrossRefGoogle Scholar
  130. Soleas GJ, Diamandis EP, Goldberg DM (1997) Resveratrol: a molecule whose time has come? And gone? Clin Biochem 30:91–113PubMedCrossRefGoogle Scholar
  131. Spadiene A, Savickiene N, Jurgeviciene N, Zalinkevicius R, Norkus A, Ostrauskas R, Skesters A, Silova A, Rodovicius H, Francaite-Daugeliene M (2013) Effect of ginkgo extract on eye microcirculation in patients with diabetes. Cent Eur J Med 8:736–741Google Scholar
  132. Stein SA, Lamos EM, Davis SN (2013) A review of the efficacy and safety of oral antidiabetic drugs. Expert Opin Drug Saf 12:153–175PubMedCrossRefGoogle Scholar
  133. Sulaiman M, Matta MJ, Sunderesan NR, Gupta MP, Periasamy M, Gupta M (2010) Resveratrol, an activator of SIRT1, upregulates sarcoplasmic calcium ATPase and improves cardiac function in diabetic cardiomyopathy. Am J Physiol Heart Circ Physiol 298:H833–H843PubMedCrossRefGoogle Scholar
  134. Suman RK, Borde MK, Mohanty IR, Maheshwari U, Deshmukh YA (2016) Myocardial salvaging effects of berberine in experimental diabetes co-existing with myocardial infarction. J Clin Diagn Res 10:FF13–FF18PubMedPubMedCentralGoogle Scholar
  135. Sun M, Estrov Z, Ji Y, Coombes KR, Harris DH, Kurzrock R (2008) Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells. Mol Cancer Ther 7:464–473PubMedCrossRefGoogle Scholar
  136. Sun C, Chen Y, Li X, Tai G, Fan Y, Zhou Y (2014) Anti-hyperglycemic and anti-oxidative activities of ginseng polysaccharides in STZ-induced diabetic mice. Food Funct 5:845–848PubMedCrossRefGoogle Scholar
  137. Sun Y, Liu Y, Chen K (2016) Roles and mechanisms of ginsenoside in cardiovascular diseases: progress and perspectives. Sci China Life Sci 59:292–298PubMedCrossRefGoogle Scholar
  138. Suresh Babu P, Srinivasan K (1995) Influence of dietary curcumin and cholesterol on the progression of experimentally induced diabetes in albino rat. Mol Cell Biochem 152:13–21Google Scholar
  139. Suryanarayana P, Satyanarayana A, Balakrishna N, Kumar PU, Reddy GB (2007) Effect of turmeric and curcumin on oxidative stress and antioxidant enzymes in streptozotocin-induced diabetic rat. Med Sci Monit 13:BR286–BR292PubMedGoogle Scholar
  140. Szablewski L (2014) Role of immune system in type 1 diabetes mellitus pathogenesis. Int Immunopharmacol 22:182–191PubMedCrossRefGoogle Scholar
  141. Szkudelski T, Szkudelska K (2015) Resveratrol and diabetes: from animal to human studies. Biochim Biophys Acta 1852:1145–1154PubMedCrossRefGoogle Scholar
  142. Takeda N (2010) Cardiac disturbances in diabetes mellitus. Pathophysiology 17:83–88PubMedCrossRefGoogle Scholar
  143. Takikawa M, Kurimoto Y, Tsuda T (2013) Curcumin stimulates glucagon-like peptide-1 secretion in GLUTag cells via Ca2+/calmodulin-dependent kinase II activation. Biochem Biophys Res Commun 435:165–170PubMedCrossRefGoogle Scholar
  144. Taliyan R, Sharma PL (2012) Protective effect and potential mechanism of Ginkgo biloba extract EGb 761 on STZ-induced neuropathic pain in rats. Phytother Res 26:1823–1829PubMedCrossRefGoogle Scholar
  145. Tang LQ, Wei W, Chen LM, Liu S (2006) Effects of berberine on diabetes induced by alloxan and a high-fat/high-cholesterol diet in rats. J Ethnopharmacol 108:109–115PubMedCrossRefGoogle Scholar
  146. Thazhath SS, Wu T, Bound MJ, Checklin HL, Standfield S, Jones KL, Horowitz M, Rayner CK (2016) Administration of resveratrol for 5 wk has no effect on glucagon-like peptide 1 secretion, gastric emptying, or glycemic control in type 2 diabetes: a randomized controlled trial. Am J Clin Nutr 103:66–70PubMedCrossRefGoogle Scholar
  147. Thirunavukkarasu M, Penumathsa SV, Koneru S, Juhasz B, Zhan L, Otani H, Bagchi D, Das DK, Maulik N (2007) Resveratrol alleviates cardiac dysfunction in streptozotocin-induced diabetes: role of nitric oxide, thioredoxin, and heme oxygenase. Free Radic Biol Med 43:720–729PubMedPubMedCentralCrossRefGoogle Scholar
  148. Timmers S, De Ligt M, Phielix E, Van De Weijer T, Hansen J, Moonen-Kornips E, Schaart G, Kunz I, Hesselink MK, Schrauwen-Hinderling VB, Schrauwen P (2016) Resveratrol as add-on therapy in subjects with well-controlled type 2 diabetes: a randomized controlled trial. Diabetes Care 39:2211–2217PubMedCrossRefGoogle Scholar
  149. Tome-Carneiro J, Larrosa M, Yanez-Gascon MJ, Davalos A, Gil-Zamorano J, Gonzalvez M, Garcia-Almagro FJ, Ruiz Ros JA, Tomas-Barberan FA, Espin JC, Garcia-Conesa MT (2013) One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol Res 72:69–82PubMedCrossRefGoogle Scholar
  150. Tosaki A, Pali T, Droy-Lefaix MT (1996) Effects of Ginkgo biloba extract and preconditioning on the diabetic rat myocardium. Diabetologia 39:1255–1262PubMedCrossRefGoogle Scholar
  151. Tsai HY, Huang PH, Lin FY, Chen JS, Lin SJ, Chen JW (2013) Ginkgo biloba extract reduces high-glucose-induced endothelial reactive oxygen species generation and cell adhesion molecule expression by enhancing HO-1 expression via Akt/eNOS and p38 MAP kinase pathways. Eur J Pharm Sci 48:803–811PubMedCrossRefGoogle Scholar
  152. Tsai CC, Chan P, Chen LJ, Chang CK, Liu Z, Lin JW (2014) Merit of ginseng in the treatment of heart failure in type 1-like diabetic rats. Biomed Res Int 2014:484161PubMedPubMedCentralGoogle Scholar
  153. Tsukita S, Yamada T, Takahashi K, Munakata Y, Hosaka S, Takahashi H, Gao J, Shirai Y, Kodama S, Asai Y, Sugisawa T, Chiba Y, Kaneko K, Uno K, Sawada S, Imai J, Katagiri H (2017) MicroRNAs 106b and 222 improve hyperglycemia in a mouse model of insulin-deficient diabetes via pancreatic β-cell proliferation. EBioMedicine 15:163–172PubMedCrossRefGoogle Scholar
  154. Voncannon JL, Jiao Y, Kim-Shapiro D, Varagic J (2014) Curcumin ameliorates cardiac dysfunction in the ovariectomized diabetic mRen2. Lewis rat by inhibiting renin angiotensin system. Hypertension 64:2CrossRefGoogle Scholar
  155. Wang LH, Yu CH, Fu Y, Li Q, Sun YQ (2011) Berberine elicits anti-arrhythmic effects via IK1/Kir2.1 in the rat type 2 diabetic myocardial infarction model. Phytother Res 25:33–37PubMedCrossRefGoogle Scholar
  156. Wang LH, Li XL, Li Q, Fu Y, Yu HJ, Sun YQ, Zhang L, Shan HL (2012) Berberine alleviates ischemic arrhythmias via recovering depressed I(to) and I(Ca) currents in diabetic rats. Phytomedicine 19:206–210PubMedCrossRefGoogle Scholar
  157. Wang CW, Su SC, Huang SF, Huang YC, Chan FN, Kuo YH, Hung MW, Lin HC, Chang WL, Chang TC (2015) An essential role of cAMP response element binding protein in Ginsenoside Rg1-mediated inhibition of Na+/glucose Cotransporter 1 gene expression. Mol Pharmacol 88:1072–1083PubMedCrossRefGoogle Scholar
  158. Wang S, Ding L, Ji H, Xu Z, Liu Q, Zheng Y (2016) The role of p38 MAPK in the development of diabetic cardiomyopathy. Int J Mol Sci 17:1037PubMedCentralCrossRefPubMedGoogle Scholar
  159. Wee JJ, Mee Park K, Chung AS (2011) Biological activities of ginseng and its application to human health. In: IFF B, Wachtel-Galor S (eds) Herbal medicine: biomolecular and clinical aspects, 2nd edn. CRC Press/Taylor & Francis Llc., Boca Raton (FL), pp 157–209CrossRefGoogle Scholar
  160. Wei S, Li W, Yu Y, Yao F, A L LX, Guan F, Zhang M, Chen L (2015) Ginsenoside compound K suppresses the hepatic gluconeogenesis via activating adenosine-5'monophosphate kinase: a study in vitro and in vivo. Life Sci 139:8–15PubMedCrossRefGoogle Scholar
  161. Whittington HJ, Babu GG, Mocanu MM, Yellon DM, Hausenloy DJ (2012) The diabetic heart: too sweet for its own good? Cardiol Res Pract 2012:845698PubMedPubMedCentralCrossRefGoogle Scholar
  162. Wongcharoen W, Phrommintikul A (2009) The protective role of curcumin in cardiovascular diseases. Int J Cardiol 133:145–151PubMedCrossRefGoogle Scholar
  163. Wu Y, Xia ZY, Dou J, Zhang L, Xu JJ, Zhao B, Lei S, Liu HM (2011) Protective effect of ginsenoside Rb1 against myocardial ischemia/reperfusion injury in streptozotocin-induced diabetic rats. Mol Biol Rep 38:4327–4335PubMedCrossRefGoogle Scholar
  164. Wu YS, Chen YT, Bao YT, Li ZM, Zhou XJ, He JN, Dai SJ, Li CY (2016) Identification and verification of potential therapeutic target genes in berberine-treated Zucker diabetic fatty rats through bioinformatics analysis. PLoS One 11:e0166378PubMedPubMedCentralCrossRefGoogle Scholar
  165. Xavier S, Sadanandan J, George N, Paulose CS (2012) Beta(2)-adrenoceptor and insulin receptor expression in the skeletal muscle of streptozotocin induced diabetic rats: antagonism by vitamin D(3) and curcumin. Eur J Pharmacol 687:14–20PubMedCrossRefGoogle Scholar
  166. Xia X, Yan J, Shen Y, Tang K, Yin J, Zhang Y, Yang D, Liang H, Ye J, Weng J (2011) Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis. PLoS One 6:e16556PubMedPubMedCentralCrossRefGoogle Scholar
  167. Xianghua F, Weili W, Yangmei Y, Xuechao W, Yanbo W, Weize F, Yunfa J, Guozhen H (2010) e0413 the adverse effects of glibenclamide on myocardial perfusion in patients with acute myocardial infarction and type 2 diabetes mellitus. Heart 96:A127–A128Google Scholar
  168. Xiao J, Sheng X, Zhang X, Guo M, Ji X (2016) Curcumin protects against myocardial infarction-induced cardiac fibrosis via SIRT1 activation in vivo and in vitro. Drug Des Devel Ther 10:1267–1277PubMedPubMedCentralGoogle Scholar
  169. Yan X, Xue J, Wu H, Wang S, Liu Y, Zheng S, Zhang C, Yang C (2015) Ginsenoside-Rb1 protects hypoxic- and ischemic-damaged cardiomyocytes by regulating expression of miRNAs. Evid Based Complement Alternat Med 2015:171306PubMedPubMedCentralGoogle Scholar
  170. Yan R, Shan H, Lin L, Zhang M, Diao JY, Li Q, Liu X, Wei J (2016) Chronic resveratrol treatment improves cardiac function in a rat model of diabetic cardiomyopathy via attenuation of mitochondrial injury and myocardial apoptosis. Int J Clin Exp Med 9:21156–21167Google Scholar
  171. Yang B, Lin H, Xiao J, Lu Y, Luo X, Li B, Zhang Y, Xu C, Bai Y, Wang H, Chen G, Wang Z (2007) The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat Med 13:486–491PubMedCrossRefGoogle Scholar
  172. Yang H, Xu W, Zhou Z, Liu J, Li X, Chen L, Weng J, Yu Z (2015) Curcumin attenuates urinary excretion of albumin in type II diabetic patients with enhancing nuclear factor erythroid-derived 2-like 2 (Nrf2) system and repressing inflammatory signaling efficacies. Exp Clin Endocrinol Diabetes 123:360–367PubMedCrossRefGoogle Scholar
  173. Yao J, Kong W, Jiang J (2015a) Learning from berberine: treating chronic diseases through multiple targets. Sci China Life Sci 58:854–859PubMedCrossRefGoogle Scholar
  174. Yao L, Wan J, Li H, Ding J, Wang Y, Wang X, Li M (2015b) Resveratrol relieves gestational diabetes mellitus in mice through activating AMPK. Reprod Biol Endocrinol 13:118PubMedPubMedCentralCrossRefGoogle Scholar
  175. Yazgan UC, Tasdemir E, Bilgin HM, Deniz Obay B, Sermet A, Elbey B (2015) Comparison of the anti-diabetic effects of resveratrol, gliclazide and losartan in streptozotocin-induced experimental diabetes. Arch Physiol Biochem 121:157–161PubMedCrossRefGoogle Scholar
  176. Yildirim SS, Akman D, Catalucci D, Turan B (2013) Relationship between downregulation of miRNAs and increase of oxidative stress in the development of diabetic cardiac dysfunction: junctin as a target protein of miR-1. Cell Biochem Biophys 67:1397–1408PubMedCrossRefGoogle Scholar
  177. Yin J, Xing H, Ye J (2008) Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism 57:712–717PubMedPubMedCentralCrossRefGoogle Scholar
  178. Yonamine CY, Pinheiro-Machado E, Michalani ML, Freitas HS, Okamoto MM, Correa-Giannella ML, Machado UF (2016) Resveratrol improves glycemic control in insulin-treated diabetic rats: participation of the hepatic territory. Nutr Metab (Lond) 13:44CrossRefGoogle Scholar
  179. Yu W, Wu J, Cai F, Xiang J, Zha W, Fan D, Guo S, Ming Z, Liu C (2012) Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats. PLoS One 7:e52013PubMedPubMedCentralCrossRefGoogle Scholar
  180. Yu W, Zha W, Ke Z, Min Q, Li C, Sun H, Liu C (2016) Curcumin protects neonatal rat cardiomyocytes against high glucose-induced apoptosis via PI3K/Akt signalling pathway. J Diabetes Res 2016:4158591PubMedPubMedCentralGoogle Scholar
  181. Yuan HD, Chung SH (2010) Protective effects of fermented ginseng on streptozotocin-induced pancreatic beta-cell damage through inhibition of NF-kappa B. Int J Mol Med 25:53–58PubMedGoogle Scholar
  182. Yuan HD, Kim JT, Kim SH, Chung SH (2012) Ginseng and diabetes: the evidences from in vitro, animal and human studies. J Ginseng Res 36:27–39PubMedPubMedCentralCrossRefGoogle Scholar
  183. Zhang XF, Liang B, Liang ZF, Lin J (2008) Effects of Gingko biloba leaf extract on learning, memory, and hippocampal amyloid precursor protein mRNA expressions in diabetic rats. Neural Regen Res 3:29–32Google Scholar
  184. Zhang H, Morgan B, Potter BJ, Ma L, Dellsperger KC, Ungvari Z, Zhang C (2010a) Resveratrol improves left ventricular diastolic relaxation in type 2 diabetes by inhibiting oxidative/nitrative stress: in vivo demonstration with magnetic resonance imaging. Am J Physiol Heart Circ Physiol 299:H985–H994PubMedPubMedCentralCrossRefGoogle Scholar
  185. Zhang H, Wei J, Xue R, Wu JD, Zhao W, Wang ZZ, Wang SK, Zhou ZX, Song DQ, Wang YM, Pan HN, Kong WJ, Jiang JD (2010b) Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism 59:285–292PubMedCrossRefGoogle Scholar
  186. Zheng B, Yang L, Wen C, Huang X, Xu C, Lee KH, Xu J (2016) Curcumin analog L3 alleviates diabetic atherosclerosis by multiple effects. Eur J Pharmacol 775:22–34PubMedCrossRefGoogle Scholar
  187. Zhi Y, Pan J, Shen W, He P, Zheng J, Zhou X, Lu G, Chen Z, Zhou Z (2016) Ginkgolide B inhibits human bladder cancer cell migration and invasion through MicroRNA-223-3p. Cell Physiol Biochem 39:1787–1794PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Salih Tunc Kaya
    • 1
  • Celal Guven
    • 2
  • Eylem Taskin
    • 3
  1. 1.Biology Department, Faculty of Arts and ScienceUniversity of DuzceDuzceTurkey
  2. 2.Biophysics Department, Faculty of MedicineUniversity of Omer HalisdemirNigdeTurkey
  3. 3.Physiology Department, Faculty of MedicineUniversity of Omer HalisdemirNigdeTurkey

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