Skip to main content

Advertisement

Log in

Potential of Natural Bioactive Compounds in Management of Diabetes: Review of Preclinical and Clinical Evidence

  • Clinical Pharmacology (L Brunetti, Section Editor)
  • Published:
Current Pharmacology Reports Aims and scope Submit manuscript

Abstract

Diabetes is one of the most common metabolic disorders often associated with hyperglycemia, altered carbohydrate, lipid, and protein metabolism. Type 2 diabetes is the most common type of diabetes associated with the disturbance of the normal level of insulin secretion from pancreatic β-cell. The current treatment of diabetes is done with semi-synthetic and synthetic drugs, but it is associated with adverse effects. Now, scientific community searches for new herbal bioactive as a replacement for successful management of the disease. Primitively bioactive compounds from herbs served as the backbone of medical therapy. The significant scientific facts and profitable dormant of ancient medicines are directed to increased global attention for herbal remedies. Herbal remedies are composed of an intricate blend of several bioactive molecules with accountable pharmacological action. Numerous published reports claim the pharmacological action of herbal remedies of the exact phytoconstituents. It is imperative to understand the pharmacokinetics of such phytoconstituents, with only a few phytoconstituents whose pharmacokinetic properties have been reported, and it requires to explore the pharmacokinetic property of other phytoconstituents. There are many bioactive plants that have antidiabetic properties such as Capsicum (chili pepper), Vitis vinifera (grape vine), Glycyrrhiza, Cinnamomum extract, Ervatamia microphylla, Trigonella foenum-graecum, and Moringa oleifera. This review highlights comprehensive information on pharmacokinetics and clinical efficacy of different bioactive constituents which is obtained from various plants that may afford as antidiabetic therapeutics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

BGL:

Blood glucose level

DIO:

Diet-induced obesity

DM:

Diabetes mellitus

GLUT-4:

Glucose transporter 4

FBG:

Fasting blood glucose

HDL:

High-density lipoprotein

HFD:

High-fructose diet

IDDM:

Insulin-dependent diabetes mellitus

LDL:

Low-density lipoprotein

NIDDM:

Non-insulin-dependent diabetes mellitus

PPAR-γ:

Peroxisome proliferator–activated receptor gamma

SREBP-1c:

Sterol regulatory element–binding protein 1c

STZ:

Streptozotocin

TC:

Total cholesterol

TG:

Triglyceride

WHO:

World Health Organization

References

  1. Baby J, Jini D. Antidiabetic effects of Momordica charantia (bitter melon) and its medicinal potency. Asian Pac J Trop Dis. 2013;3(2):93–102.

    Article  Google Scholar 

  2. Shidfar F, Heydari I, Hajimiresmaiel SJ, Hosseini S, Shidfar S, Amiri F. The effects of cranberry juice on serum glucose, apoB, apoA-I, Lp(a), and paraoxonase-1 activity in type 2 diabetic male patients. J Res Med Sci. 2012;17:355–60.

  3. Frati AC, Jiminez E, Raoul Ariza C. Hypoglycaemic effect of Opuntia ficus indica in non-insulin-dependent diabetes mellitus patients. Phytother Res. 1990;4:195–7.

    Article  Google Scholar 

  4. Medagama AB. The glycaemic outcomes of cinnamon, a review of the experimental evidence and clinical trials. Nutr J. 2015;14:108.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Williams G, Pick JC. Textbook of diabetes II. Oxford: Blackwell; 1991. p. 977–93.

    Google Scholar 

  6. Wainstein J, Ganz T, Boaz M, Dayan YB, Dolev E, Kerem Z, et al. Olive leaf extract as a hypoglycemic agent in both human diabetic subjects and in rats. J Med Food. 2012;15(7):26.

    Article  Google Scholar 

  7. Singh V, Singh SP, Singh M, Gupta AK, Kumar A. Combined potentiating action of phytochemical(s) from Cinnamomum tamala and Aloe vera for their anti-diabetic and insulinomimetic effect using in vivo rat and in vitro NIH/3 T3 cell culture system. Appl Biochem Biotechnol. 2015;175:2542–63.

    Article  CAS  PubMed  Google Scholar 

  8. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, Colagiuri S, Guariguata L, Motala AA, Ogurtsova K, Shaw JE, Bright D, Williams R. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9th edition. 2019;157:107843.

  9. Patel D, Prasad S, Kumar R, Hemalatha S. An overview on antidiabetic medicinal plants having insulin mimetic property. Asian Pac J Trop Biomed. 2012;2:320–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Arulselvan P, Ghofar HAA, Karthivashan G, Halim MFA, Ghafar MSA, Fakurazi S. Antidiabetic therapeutics from natural source: a systematic review. Biomed Prev Nutr. 2014;4:607–17.

    Article  Google Scholar 

  11. Allen FM. Blueberry leaf extract. Physiologic and clinical properties in relation to carbohydrate metabolism. JAMA. 1927;89:1577–81.

    Article  CAS  Google Scholar 

  12. Asgary S, Rafieian Kopaei M, Sahebkar A, Shamsi F, Goli-malekabadi N. Anti-hyperglycemic and anti-hyperlipidemic effects of Vaccinium myrtillus fruit in experimentally induced diabetes (antidiabetic effect of Vaccinium myrtillus fruit). J Sci Food Agric. 2016;96(3):764–8.

    Article  CAS  PubMed  Google Scholar 

  13. Sidorova Y, Shipelin V, Mazo V, Zorin S, Petrov N, Kochetkova A. Hypoglycemic and hypolipidemic effect of Vaccinium myrtillus L. leaf and Phaseolus vulgaris L. seed coat extracts in diabetic rats. Nutrition. 2017;41:107–12.

    Article  PubMed  Google Scholar 

  14. Bhaskar S, Sufiyan S, Gurudayal R, Manisha C, Gaurav S. Hypoglycemic and hepatoprotective effects of processed Aloe vera gel in a mice model of alloxan induced diabetes mellitus. J Diabetes Metab. 2013;4:9.

    Google Scholar 

  15. Agarwal V, Sharma AK, Upadhyay A, Singh G, Gupta R. Hypoglycemic effects of Citrullus colocynthis roots. Acta Pol Pharm. 2012;69(1):75–9.

    PubMed  Google Scholar 

  16. Kim K, Kim H, Kwon J, Lee S, Kong H, Im SA, et al. Hypoglycemic and hypolipidemic effects of processed Aloe vera gel in a mouse model of non-insulin-dependent diabetes mellitus. Phytomedicine. 2009;16(9):856–63.

    Article  PubMed  Google Scholar 

  17. Rajasekaran S, Sivagnanam K, Ravi K, Subramanian S. Beneficial effects of Aloe vera gel extract on lipid profile status in rats with streptozotocin diabetes. Clin Exp Pharmacol Physiol. 2006;33(3):232–7.

    Article  CAS  PubMed  Google Scholar 

  18. Attele AS, Zhou Y-P, Xie J-T, Wu JA, Zhang L, Dey L, et al. Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component. Diabetes. 2002;51:1851–8.

    Article  CAS  PubMed  Google Scholar 

  19. Kim JH, Hahm DH, Yang DC, Kim JH, Lee HJ, Shim I. Effect of crude saponin of Korean red ginseng on high-fat diet-induced obesity in the rat. J Pharmacol Sci. 2005;97(1):124–31.

    Article  CAS  PubMed  Google Scholar 

  20. Lee KT, Jung TW, Lee HJ, Kim SG, Shin YS, Whang WK. The antidiabetic effect of ginsenoside Rb2 via activation of AMPK. Arch Pharm Res. 2011;34(7):1201–8.

    Article  CAS  PubMed  Google Scholar 

  21. Amin KA, Awad EM, Nagy MA. Effects of Panax quinquefolium on streptozotocin-induced diabetic rats: role of C-peptide, nitric oxide and oxidative stress. Int J Clin Exp Med. 2011;4(2):136–47.

    PubMed  PubMed Central  Google Scholar 

  22. Yoon JW, Kang SM, Vassy JL, Shin H, Lee YH, Ahn HY, et al. Efficacy and safety of ginsam, a vinegar extract from Panax ginseng, in type 2 diabetic patients: results of a double-blind, placebo-controlled study. J Diabetes Investig. 2012;3:309–17.

    Article  CAS  PubMed  Google Scholar 

  23. Vijaya K, Sunitha SP, Husssain JA, Sandhya P, Sujatha D, Gopireddy G. Synergistic antihyperglycemic, antihyperlipidemic and antioxidant effects of Momordica charantia and metformin in streptozotocin induced diabetic rats. World J Pharm Res. 2014;3:1901–80.

    Google Scholar 

  24. Eidi A, Eidi M, Esmaeili E. Antidiabetic effect of garlic (Allium sativum L.) in normal and streptozotocin-induced diabetic rats. Phytomedicine. 2006;13(9–10):624–9.

    Article  CAS  PubMed  Google Scholar 

  25. Thomson M, Al-Amin ZM, Al-Qattan KK, Shaban LH, Ali M. Antidiabetic and hypolipidaemic properties of garlic (Allium sativum) in streptozotocin-induced diabetic rats. Int J Diabetes Metab. 2007;15:108–15.

    Google Scholar 

  26. Otunola GA, Afolayan AJ. Antidiabetic effect of combined spices of Allium sativum, Zingiber officinale and Capsicum frutescens in alloxan-induced diabetic rats. 2015;8(4):314–23.

  27. Xue WL, Li XS, Zhang J, Liu YH, Wang ZL, Zhang RJ. Effect of Trigonella foenum-graecum (fenugreek) extracts on blood glucose, blood lipid and hemorheological properties in streptozotocin-induced diabetic rats. Asia Pac J Clin Nutr. 2007;16(S1):422–6.

    CAS  PubMed  Google Scholar 

  28. Annida B, Stanely Mainzen Prince P. Supplementation of fenugreek leaves lower lipid profile in streptozotocin-induced diabetic rats. J Med Food. 2004;7(2):153–6.

    Article  CAS  PubMed  Google Scholar 

  29. Abou El-Soud NH, Khalil MY, Hussein JS, Oraby FSH, Hussein Farrag AR. Antidiabetic effects of fenugreek alkaliod extract in streptozotocin induced hyperglycemic rats. J Appl Sci Res. 2007;3(10):1073–83.

    Google Scholar 

  30. Kim K, Kim H, Kwon J, Lee S, Kong H, Im SA, Lee YL, Lee YR, Oh ST, Jo TH, Park YI, Lee CK, Kim K. Hypoglycemic and hypolipidemic effects of processed Aloe vera gel in a mouse model of non-insulin-dependent diabetes mellitus. Phytomedicine. 2009;16(9):856–63.

  31. Jin Y, Shi Y, Zou Y,Miao C, Sun B, Li C. Fenugreek prevents thedevelopment of STZ-induced diabetic nephropathy in a rat modelof diabetes. Evid Based Complement Alternat Med. 2014; 2014:259368.

  32. Anand P, Murali KY, Tandon V, Murthy PS, Chandra R. Insulinotropic effect of cinnamaldehyde on transcriptional regulation of pyruvate kinase, phosphoenolpyruvate carboxykinase, and GLUT4 translocation in experimental diabetic rats. Chem Biol Interact. 2010;186(1):72–81.

  33. Asmena M, Alauddin M, Md Atiar R, Kabir A. Antihyperglycemic effect of Trigonella foenum-graecum (fenugreek) seed extract in alloxan-induced diabetic rats and its use in diabetes mellitus: a brief qualitative phytochemical and acute toxicity test on the extract. Afr J Tradit Complement Altern Med. 2009;6(3):255–61.

    Google Scholar 

  34. Khosrozadeh M, Heydari N, Abootalebi M. The effect of Abelmoschus esculentus on blood levels of glucose in diabetes mellitus. Iran J Med Sci. 2016;41(3):S63.

    PubMed  PubMed Central  Google Scholar 

  35. Kim SH, Hyun SH, Choung SY. Anti-diabetic effect of cinnamon extract on blood glucose in db/db mice. J Ethnopharmacol. 2006;104(1–2):119–23.

    Article  PubMed  Google Scholar 

  36. Zang Y, Igarashi K, Li Y. Anti-diabetic effects of luteolin and luteolin-7-O-glucoside on KK-A(y) mice. Biosci Biotechnol Biochem. 2016;80(8):1580–6.

    Article  CAS  PubMed  Google Scholar 

  37. Hoggard N, Cruickshank M, Moar KM, Bestwick C, Holst JJ, Russell W, et al. A single supplement of a standardised bilberry (Vaccinium myrtillus L.) extract (36 % wet weight anthocyanins) modifies glycaemic response in individuals with type 2 diabetes controlled by diet and lifestyle. J Nutr Sci. 2013;2:e22.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Shukla K, Narain JP, Puri P, Gupta A, Bijlani RL, Mahapatra SC, et al. Glycaemic response to maize, bajra and barley. Indian J Physiol Pharmacol. 1991;35:249–54.

    CAS  PubMed  Google Scholar 

  39. Taukoorah U, Mahomoodally MF. Crude Aloe vera gel shows antioxidant propensities and inhibits pancreatic lipase and glucose movement in vitro. Adv Pharmacol Sci. 2016;2016:3720850.

    PubMed  PubMed Central  Google Scholar 

  40. Zhang Y, Liu W, Liu D, Zhao T, Tian H. Efficacy of Aloe vera supplementation on prediabetes and early non-treated diabetic patients: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2016;8(7):E388.

    Article  PubMed  Google Scholar 

  41. Tanaka M, Misawa E, Ito Y, Habara N, Nomaqushi K, Yamada M, et al. Identification of five phytosterols from Aloe vera gel as anti-diabetic compounds. Biol Pharm Bull. 2006;29(7):1418–22.

    Article  CAS  PubMed  Google Scholar 

  42. Yongchaiyudha S, Rungpitarangsi V, Bunyapraphatsara N, Chokechaijaroenporn O. Antidiabetic activity of Aloe vera L. juice. I. Clinical trial in new cases of diabetes mellitus. Phytomedicine. 1996;3(3):241–3.

    Article  CAS  PubMed  Google Scholar 

  43. Can A, Akev N, Ozsoy N, Bolkent S, Arda BP, Yanardag R, et al. Effect of Aloe vera leaf gel and pulp extracts on the liver in type-II diabetic rat models. Biol Pharm Bull. 2004;27(5):694–8.

    Article  CAS  PubMed  Google Scholar 

  44. Wang GG, Lu XH, Li W, Zhao X, Zhang C. Protective effects of luteolin on diabetic nephropathy in STZ-induced diabetic rats. Evid Based Complement Alternat Med. 2011;2011:3231.

    Article  Google Scholar 

  45. Itankar PR, Lokhande SJ, Verma PR, Arora SK, Sahu RA, Patil AT. Antidiabetic potential of unripe Carissa carandas Linn. fruit extract. J Ethnopharmacol. 2011;135:430–3.

    Article  CAS  PubMed  Google Scholar 

  46. El-Zein O, Kreydiyyeh SI. Pine bark extract inhibits glucose transport in enterocytes via mitogen-activated kinase and phosphoinositol 3-kinase. Nutrition. 2011;27:707–12.

    Article  PubMed  Google Scholar 

  47. Kulling SE, Rawel HM. Chokeberry (Aronia melanocarpa) – a review on the characteristic components and potential health effects. Planta Med. 2008;74(13):1625–34.

    Article  CAS  PubMed  Google Scholar 

  48. Dey L, Xie JT, Wang A, Wu J, Maleckar SA, Yuan CS. Anti-hyperglycemic effects of ginseng: comparison between root and berry. Phytomedicine. 2003;10(6–7):600–5.

    Article  CAS  PubMed  Google Scholar 

  49. Chuengsamarn SS, Rattanamongkolgul R, Luechapudiporn C, Phisalaphong SJ. Curcumin extract for prevention of type 2 diabetes. Diabetes Care. 2012;35(11):2121–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Michael B, Krawinkel MD, Gudrun B, Keding MS. Bitter gourd (Momordica charantia): a dietary approach to hyperglycemia. Nutr Rev. 2006;64:331–7.

    Article  Google Scholar 

  51. Fernando MR, Wickramasinghe N, Thabrew MI, Ariyananda PL, Karunanayake EH. Effect of Artocarpus heterophyllus and Asteracanthus longifolia on glucose tolerance in normal human subjects and in maturity-onset diabetic patients. J Ethnopharmacol. 1991;31:277–82.

    Article  CAS  PubMed  Google Scholar 

  52. Frati AC, Gordillo BE, Altamirano P, Ariza CR, Cortes-Franco R, Chavez-Negrete A. Acute hypoglycemic effect of Opuntia streptacantha Lemaire in NIDDM. Diabetes Care. 1990;13:455–6.

    Article  CAS  PubMed  Google Scholar 

  53. Ahmad N, Hassan MR, Halder H, Bennoor KS. Effect of Momordica charantia (Karolla) extracts on fasting and postprandial serum glucose levels in NIDDM patients. Bangladesh Med Res Counc Bull. 1999;25(1):11–3.

    CAS  PubMed  Google Scholar 

  54. Al-Khazraji SM, Al-Shamaony LA, Twaij HA. Hypoglycaemic effect of Artemisia herba alba. Effect of different parts and influence of the solvent on hypoglycaemic activity. J Ethnopharmacol. 1993;40:163–6.

    Article  CAS  PubMed  Google Scholar 

  55. Patel JC, Dhirawani MK, Doshi JC. Karella in the treatment of diabetes mellitus. Indian J Med Sci. 1968;22(1):30–2. 48.

    CAS  PubMed  Google Scholar 

  56. Baldwa VS, Bhandari CM, Pangaria A, Goyal RK. Clinical trial in patients with diabetes mellitus of an insulin-like compound obtained from plant source. Ups J Med Sci. 1977;82(1):39–41.

    Article  CAS  PubMed  Google Scholar 

  57. Al-Habori M, Raman A, Lawrence MJ, Skett P. In vitro effect of fenugreek extracts on intestinal sodium-dependent glucose uptake and hepatic glycogen phosphorylase A. Int J Expt Diabetes Res. 2001;2(2):91–9.

    Article  CAS  Google Scholar 

  58. Gupta A, Gupta R, Lal B. Effect of Trigonella foenum-graecum (fenugreek) seeds on glycemic control and insulin resistance in type 2 diabetes mellitus: a double blind placebo controlled study. J Assoc Physicians India. 2001;49:1057–61.

    CAS  PubMed  Google Scholar 

  59. Patel MM, Mishra S. A kinetic study for in-vitro intestinal uptake of monosaccharide across rat everted gut sacs in the presence of some antidiabetic medicinal plants. Internet J Altern Med. 2009;7(1):1–7.

    Google Scholar 

  60. Madar Z, Abel R, Samish S, Arad J. Glucose-lowering effect of fenugreek in non-insulin dependent diabetics. Eur J Clin Nutr. 1988;42(1):51–4.

    CAS  PubMed  Google Scholar 

  61. Moorthy R, Prabhu KM, Murthy PS. Anti-hyperglycemic compound (GII) from fenugreek (Trigonella foenum-graecum Linn.) seeds, its purification and effect in diabetes mellitus. Indian J Exp Biol. 2010;48(11):1111–8.

    PubMed  Google Scholar 

  62. Sharma RD, Raghuram TC, Rao NS. Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes. Eur J Clin Nutr. 1990;44(4):301–6.

    CAS  PubMed  Google Scholar 

  63. Kohli K, Singh R. A clinical trial of jambu (Eugenia jambolana) in non-insulin dependent diabetes mellitus. J Res Ayurveda Siddha. 1993;13:89–97.

    Google Scholar 

  64. Srivastava Y, Bhatt H, Gupta O, Gupta P. Hypoglycemia induced by Syzygium cumini Linn. seeds in diabetes mellitus. Asian Med J. 1983;26:489–92.

    Google Scholar 

  65. Sauvaire Y, Petit P, Broca C, Manteghetti M, Baissac Y, Fernandez-Alvarez J, et al. 4-Hydroxyisoleucine: a novel amino acid potentiator of insulin secretion. Diabetes. 1998;47(2):206–10.

    Article  CAS  PubMed  Google Scholar 

  66. Teixeira CC, Fuchs FD, Weinert LS, Esteves MDJ. The efficacy of folk medicines in the management of type 2 diabetes mellitus: results of a randomized controlled trial of Syzygium cumini (L.) Skeels. J Clin Pharm Ther. 2006;31(1):1–5.

  67. Deguchi YK, Osada KU, Kimura H, Oshikawa MY, Kudo T, Yasui H, et al. Effects of extract of guava leaves on the development of diabetes in the db/db mouse and on the postprandial blood glucose of human subjects. Nippon Nogei Kagaku Kaishi. 1998;72:923–31.

    Article  CAS  Google Scholar 

  68. Wu Z, Luo JZ, Luo L. American ginseng modulates pancreatic beta cell activities. Chin Med. 2007;2:11–0.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Krawinkel MB, Keding GB. Bitter gourd (Momordica charantia): a dietary approach to hyperglycemia. Nutr Rev. 2006;64:331–7.

    Article  PubMed  Google Scholar 

  70. Fuangchan A, Sonthisombat P, Seubnukarn T, Chanouan R, Chotchaisuwat P, Sirigulsatien V, et al. Hypoglycemic effect of bitter melon compared with metformin in newly diagnosed type 2 diabetes patients. J Ethnopharmacol. 2011;134(2):422–8.

    Article  PubMed  Google Scholar 

  71. Ghosh D, Konishi T. Anthocyanins and anthocyanin-rich extracts: role in diabetes and eye function. Asia Pac J Clin Nutr. 2007;16(2):200–8.

    CAS  PubMed  Google Scholar 

  72. Martineau LC, Couture A, Spoor D, Benhaddou-Andaloussi A, Harris C, Meddah B, et al. Anti-diabetic properties of the Canadian low bush blueberry Vaccinium angustifolium Ait. Phytomedicine. 2006;13(9–10):612–23.

    Article  CAS  PubMed  Google Scholar 

  73. Liu J, Gao F, Ji B, Wang R, Yang J, Liu H, et al. Anthocyanins-rich extract of wild Chinese blueberry protects glucolipotoxicity-induced INS832/13 β-cell against dysfunction and death. J Food Sci Technol. 2015;52(5):3022–9.

    Article  CAS  PubMed  Google Scholar 

  74. Saha RK, Nesa A, Nahar K, Akter M. Anti-diabetic activities of the fruit Aegle mamelos. J Mol Biomark Diagn. 7:272.

  75. Sahib AS. Anti-diabetic and antioxidant effect of cinnamon in poorly controlled type-2 diabetic Iraqi patients: a randomized, placebo-controlled clinical trial. J Intercult Ethnopharmacol. 2016;5(2):108–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Esra S, Sievenpiper JL, Vladimir D, Adrian IC, Ha V, Viranda HJ, et al. The effect of ginseng (the genus Panax) on glycemic control: a systematic review and meta-analysis of randomized controlled clinical trials. PLoS One. 2014;9(9):e107391.

    Article  Google Scholar 

  77. Kim HO, Park M, Han J. Effects of fermented red ginseng supplementation on blood glucose and insulin resistance in type 2 diabetic patients. J Korean Soc Food Sci Nutr. 2011;40:696–703.

    Article  CAS  Google Scholar 

  78. Kim JH, Kang MJ, Choi HN, Jeong SM, Lee YM, Kim JI. Quercetin attenuates fasting and postprandial hyperglycemia in animal models of diabetes mellitus. Nutr Res Pract. 2011;5:107–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Shin SK, Kwon JH, Jeong YJ, Jeon SM, Choi JY, Choi MS. Supplementation of cheonggukjang and red ginseng cheonggukjang can improve plasma lipid profile and fasting blood glucose concentration in subjects with impaired fasting glucose. J Med Food. 2011;14:108–13.

    Article  PubMed  Google Scholar 

  80. Mucalo I, Rahelic D, Jovanovski E, Bozikov V, Romic Z, et al. Effect of American ginseng (Panax quinquefolius L.) on glycemic control in type 2 diabetes. Coll Antropol. 2012;36:1435–40.

    PubMed  Google Scholar 

  81. Chang CLT, Lin Y, Bartolome AP, Chen YC, Chiu SC, Yang WC. Herbal therapies for type 2 diabetes mellitus: chemistry, biology, and potential application of selected plants and compounds. Evid Based Complement Alternat Med. 2013;2013:378657.

  82. Saeed MK, Shahzadi I, Ahmad I, Ahmad R, Shahzad K, Ashraf M, et al. Nutritional analysis and antioxidant activity of bitter gourd (Momordica charantia) from Pakistan. Pharmacol Online. 2010;1:252–60.

    Google Scholar 

  83. Chang CI, Chen CR, Liao YW, Cheng HL, Chen YC, Chou CH. Cucurbitane-type triterpenoids from Momordica charantia. J Nat Prod. 2006;71:1327–30.

    Article  Google Scholar 

  84. Sekar DS, Sivagnanam K, Subramanian S. Antidiabetic activity of Momordica charantia seeds on streptozotocin induced diabetic rats. Pharmazie. 2005;60(5):383–7.

    CAS  PubMed  Google Scholar 

  85. Dans AML, Villarruz MVC, Jimeno CA, Javelosa MAU, Chua J, Bautista R, et al. The effect of Momordica charantia capsule preparation on glycemic control in type 2 diabetes mellitus needs further studies. J Clin Epidemiol. 2007;60(6):554–9.

    Article  PubMed  Google Scholar 

  86. Uebanso T, Arai H, Taketani Y, Fukaya M, Yamamoto H, Mizuno A, et al. Extracts of Momordica charantia suppress postprandial hyperglycemia in rats. J Nutr Sci Vitaminol (Tokyo). 2007;53(6):482–8.

    Article  CAS  Google Scholar 

  87. Cummings E, Hundal HS, Wackerhage H, Hope M, Belle M, Adeghate E, et al. Momordica charantia fruit juice stimulates glucose and amino acid uptakes in L6 myotubes. Mol Cell Biochem. 2004;261(1–2):99–104.

    Article  CAS  PubMed  Google Scholar 

  88. Tongia A, Tongia SK, Dave M. Phytochemical determination and extraction of Momordica charantia fruit and its hypoglycemic potentiation of oral hypoglycemic drugs in diabetes mellitus (NIDDM). Indian J Physiol Pharmacol. Apr 2004;48(2):241–4.

    CAS  PubMed  Google Scholar 

  89. Barrie SA, Jonathan ND, Wright MD, Pizzorno ND. Effects of garlic oil on platelet aggregation, serum lipids and blood pressure in humans. J Orthomol Med. 1987;2:15–21.

    Google Scholar 

  90. Aaron C. Garlic & life. N Am Rev. 1996;281:14–24.

    Google Scholar 

  91. Colín-González AL, Santana RA, Silva-Islas CA, Chánez-Cárdenas ME, Santamaría A, Maldonado PD. The antioxidant mechanisms underlying the aged garlic extract- and S-allylcysteine-induced protection. Oxidative Med Cell Longev. 2012;2012:907162.

    Article  Google Scholar 

  92. Bayan L, Koulivand PH, Gorji A. Garlic: a review of potential therapeutic effects. Avicenna J Phytomed. 2014;4:1–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Atkin M, Laight D, Cummings MH. The effects of garlic extract upon endothelial function, vascular inflammation, oxidative stress and insulin resistance in adults with type 2 diabetes at high cardiovascular risk. A pilot double blind randomized placebo controlled trial. J Diabetes Complicat. 2016;30(4):723–7.

    Article  Google Scholar 

  94. Padiya R, Banerjee SK. Garlic as an anti-diabetic agent: recent progress and patent reviews. Recent Pat Food Nutr Agric. 2013;5(2):105–27.

    Article  CAS  PubMed  Google Scholar 

  95. Huang DW, Chang WC, Wu JS, Shih RW, Shen SC. Gallic acid ameliorates hyperglycemia and improves hepatic carbohydrate metabolism in rats fed a high-fructose diet. Nutr Res. 2016;36(2):150–60.

    Article  CAS  PubMed  Google Scholar 

  96. Chourey S, Narsinghani T, Soni LK. Effect of Allium sativum on the pharmacokinetic of metformin in rat plasma: a herb-drug interaction study. Scholars Research Library Der Pharma Chemica. 2011;3(2):287–91.

    CAS  Google Scholar 

  97. Ashraf R, Khan RA, Ashraf I. Garlic (Allium sativum) supplementation with standard antidiabetic agent provides better diabetic control in type 2 diabetes patients. Pak J Pharm Sci. 2011;24(4):565–70.

    CAS  PubMed  Google Scholar 

  98. Ashraf R, Aamir K, Shaikh AR, Ahmed T. Effects of garlic on dyslipidemia in patients with type 2 diabetes mellitus. J Ayub Med Coll Abbottabad. 2005;17(3):60–4.

    PubMed  Google Scholar 

  99. Sharma RD, Raghuram TC, Rao NS. Effect of fenugreek seeds on blood glucose and serum lipids in type 1 diabetes. Eur J Clin Nutr. 1990;44(4):301–6.

    CAS  PubMed  Google Scholar 

  100. Valette G, Sauvaire Y, Baccou JC, Ribes G. Hypocholesterolaemic effect of fenugreek seeds in dogs. Atherosclerosis. 1984;50:105–11.

    Article  CAS  PubMed  Google Scholar 

  101. Shani J, Goldschimied A, Joseph B, Ah Aronson Z, Sulman FG. Hypoglycemic effect of Trigonella foenum graecum and Lupinus termis (Leguminosae) and their major alkaloids in alloxan-induced diabetic and normal rats. Arch Int Pharmacodyn Ther. 1974;210:27–37.

    CAS  Google Scholar 

  102. Amin R, Abdul Ghani AS, Suleiman MS. Effect of fenugreek and lupine seeds on the development of experimental diabetes in rats. Planta Med. 1988;54:286–90.

    Article  Google Scholar 

  103. Hannan JMA, Rokeya B, Faruque O, Nahar N, Moshiuzzaman M, Azad Khan AK, et al. Effect of soluble dietary fibre fraction of Trigonella foenum graecum on glycemic, insulinemic, lipidemic and platelet aggregation status of type 2 diabetic model rats. J Ethnopharmacol. 2003;88:73–7.

    Article  CAS  PubMed  Google Scholar 

  104. Neelakantan N, Narayanan M, de Souza RJ, van Dam RM. Effect of fenugreek (Trigonella foenum-graecum L.) intake on glycemia: a meta-analysis of clinical trials. Nutr J. 2014;18:13–7.

    Google Scholar 

  105. Mohammad Y, Mohammad I. Clinical evaluation of antidiabetic activity of Trigonella seeds and Aegle marmelos leaves. World Appl Sci J. 2009;7(10):1231–4.

    Google Scholar 

  106. Khan A, Bryden NA, Polansky MM, Anderson RA. Insulin potentiating factor and chromium content of selected foods and spices. Biol Trace Elem Res. 1990;24:183–8.

    Article  CAS  PubMed  Google Scholar 

  107. Anderson RA, Broadhurst CL, Polansky MM, Schmidt WF, Khan A, Flanagan VP, et al. Isolation and characterization of polyphenol type-A polymers from cinnamon with insulin-like biological activity. J Agric Food Chem. 2004 Jan 14;52(1):65–70.

    Article  CAS  PubMed  Google Scholar 

  108. Adisakwattana S, Lerdsuwankij O, Poputtachai U, Minipun A, Suparpprom C. Inhibitory activity of cinnamon bark species and their combination effect with acarbose against intestinal α-glucosidase and pancreatic α-amylase. Plant Foods Hum Nutr. 2011 Jun;66(2):143–8.

    Article  CAS  PubMed  Google Scholar 

  109. Hlebowicz J, Hlebowicz A, Lindstedt S, Björgell O, Höglund P, Holst JJ, et al. Effects of 1 and 3 g cinnamon on gastric emptying, satiety, and postprandial blood glucose, insulin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and ghrelin concentrations in healthy subjects. Am J Clin Nutr. 2009;89(3):815–21.

    Article  CAS  PubMed  Google Scholar 

  110. Zhu R, Liu H, Chenyue Liu, Wang L, Rufeng Ma R, Chen B, Li L, Niu J, Fu M, Zhang D, Gao S. Cinnamaldehyde in diabetes: A review of pharmacology, pharmacokinetics and safety. Pharmacol Res. 2017;122:78–89.

  111. Kirkham S, Akilen R, Sharma S, Tsiami A. The potential of cinnamon to reduce blood glucose levels in patients with type 2 diabetes and insulin resistance. Diabetes Obes Metab. 2009;11(12):1100–13.

    Article  CAS  PubMed  Google Scholar 

  112. Khan R, Khan Z, Shah SH. Cinnamon may reduce glucose, lipid and cholesterol level in type 2 diabetic individuals. Pak J Nutr. 2010;9(5):430–3.

    Article  CAS  Google Scholar 

  113. Pham AQ, Kourlas H, Pham DQ. Cinnamon supplementation in patients with type 2 diabetes mellitus. Pharmacotherapy. 2007;27(4):595–9.

    Article  CAS  PubMed  Google Scholar 

  114. Mang B, Wolters M, Schmitt B, Kelb K, Lichtinghagen R, Stichtenoth DO, et al. Effects of a cinnamon extract on plasma glucose, HbA, and serum lipids in diabetes mellitus type 2. Eur J Clin Investig. 2006;36(5):340–4.

    Article  CAS  Google Scholar 

  115. Suppapitiporn S, Kanpaksi N, Suppapitiporn S. The effect of Cinnamon cassia powder in type 2 diabetes mellitus. J Med Assoc Thail. 2006;89(3):S200–5.

    Google Scholar 

  116. Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. 2003;26(12):3215–8.

    Article  PubMed  Google Scholar 

  117. Lu F, BoLi YL. Okara dietary fiber and hypoglycemic effect of okara foods. Bioact Carbohydr Diet Fibre. 2013;2(2):126–32.

    Article  CAS  Google Scholar 

  118. Martin FW. Okra, potential multiple purpose crop for the temperate zones and tropics. Econ Bot. 1982;36(3):340–5.

    Article  Google Scholar 

  119. Sabitha V, Ramachandran S, Naveen KR, Panneerselvam K. Antidiabetic and antihyperlipidemic potential of Abelmoschus esculentus (L.) Moench. in streptozotocin-induced diabetic rats. J Pharm Bioallied Sci. 2013;3(3):397–402.

    Google Scholar 

  120. Shridhar PBS, Rao SM, Byregowda ML, Satyanarayana, Purushotham KM. Antidiabetic effect of Gymnema sylvestre in streptozotocin induced diabetes in rats. Braz J Vet Pathol. 2015;8(2):36–45.

    Google Scholar 

  121. Shanmugasundaram ER, Rajeswari G, Baskaran K, Rajesh Kumar BR, Radha Shanmugasundaran K, Kizar AB. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. J Ethnopharmacol. 1990;30:281–94.

    Article  CAS  PubMed  Google Scholar 

  122. Al-Romaiyan A, King AJ, Persaud SJ, Jones PM. A novel extract of Gymnema sylvestre improves glucose tolerance in vivo and stimulates insulin secretion and synthesis in vitro. Phytother Res. 2013;27:1006–11.

    Article  CAS  PubMed  Google Scholar 

  123. Al-Romaiyan AB, Liu H, Asare-Anane CR, Maity SK, Chatterjee N, Koley TB, et al. A novel Gymnema sylvestre extract stimulates insulin secretion from human islets in vivo and in vitro. Phytother Res. 2010;24:1370–6.

    Article  CAS  PubMed  Google Scholar 

  124. Cooper TH, Clark JG, Guzinski JA. In: Ho CT, Osawa T, Rosen T, editors. Food phytochemicals for cancer prevention II: teas, spices, and herbs, vol. 23. Washington DC: American Chemical Society; 1994. p. 231–6.

    Chapter  Google Scholar 

  125. Olatunde A, Joel EB, Tijjani H, Obidola SM, Luka CD. Anti-diabetic activity of aqueous extract of Curcuma longa (Linn) rhizome in normal and alloxan-induced diabetic rats. Researcher. 2014;6(7):58–65.

    Google Scholar 

  126. Pandey KB, Rizvi SI. Role of red grape polyphenols as antidiabetic agents. Integr Med Res. 2014;3:119–25.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Pietta P, Minoggio M, Bramati L. Plant polyphenols: structure, occurrence and bioactivity. Stud Nat Prod Chem. 2003;28:257–312.

    Article  CAS  Google Scholar 

  128. Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr. 2004;79:727–47.

    Article  CAS  PubMed  Google Scholar 

  129. Adlercreutz H. Lignans and human health. Crit Rev Clin Lab Sci. 2007;44:483–525.

    Article  CAS  PubMed  Google Scholar 

  130. Coskun O, Kanter M, Korkmaz A, Oter Quercetin S. A flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and β-cell damage in rat pancreas. Pharmacol Res. 2005;51:117–23.

    Article  CAS  PubMed  Google Scholar 

  131. Yanqing Z, Sato H, Kiharu I. Anti-diabetic effects of a kaempferol glycoside-rich fraction from unripe soybean (edamame, Glycine max L. Merrill. ‘Jindai’) leaves on KK-Ay mice. Biosci Biotechnol Biochem. 2011;75(9):1677–84.

    Article  Google Scholar 

  132. Zang Y, Zhang L, Igarashi K, Yu C. The anti-obesity and anti-diabetic effects of kaempferol glycosides from unripe soybean leaves in high-fat-diet mice. Food Funct. 2015;6(3):834–41.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ameeduzzafar Zafar.

Ethics declarations

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Clinical Pharmacology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zafar, A., Alruwaili, N.K., Panda, D.S. et al. Potential of Natural Bioactive Compounds in Management of Diabetes: Review of Preclinical and Clinical Evidence. Curr Pharmacol Rep 7, 107–122 (2021). https://doi.org/10.1007/s40495-021-00255-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40495-021-00255-8

Keywords

Navigation