Insight Mode of Action and Phytochemistry of Reported Medicinal Plant with Possible Antidiabetic Activity

Santosh Kumar Jha1,2*, D. P. Chatterjee2 

1Om Sadashiva College ofPharmacy,Sagdaha,Jasidih,Deoghar, Jharkhand, India

2Institute of Pharmaceutical Sciences, SAGE University, Indore (MP), India

Received: 10-Jul-2020 , Accepted: 18-Dec-2020

Keywords: Antidiabetic Activity, Phytochemistry, Medicinal plant

DOI: http://dx.doi.org/10.20510/ukjpb/8/i6/1611052005

Full-Text PDF      

XML                    

Google Scholar  

How To Cite       

Abstract

Diabetes become very common in people of developed countries due to their changed food habit and no physical activity. The various types of synthetic medicines are available for the management of diabetes. These medicines are associated with the side effects. Apart from this, the alternative medicines such as herbal drug are the best option for the treatment of diabetes. The herbal medicines are free from any type of side effects, and presently their demands are increased. The herbal drugs are available in different dosage form. The numerous medicinal plants have been scientifically reported antidiabetic property by the researchers. The review paper highlights the plants having antidiabetic activity with their phytochemistry and possible mechanism of action. Additionally, the active constituents responsible for antidiabetic activity are also illustrated.           

1 Introduction

Diabetes is one of the significant endocrine infections which influences a great many individuals in the industrial and developing countries. It is extended that the all out number of individuals with diabetes overall is relied upon to increment to 592 million by 2035. Diabetes is a metabolic infection described by inadequate insulin emission, impeded cell activity of the insulin or both. The trademark side effects of diabetes are pruritus, polydipsia, weight reduction, polyphagia, squandering, obscured vision, polyuria, tachycardia and hypotension. Dietary and way of life factors (Obesity, weight acquire, actual dormancy and low fiber diet with a high glycemic file) assume a huge part in the improvement of diabetes1-6.

The treatment convention requires a multimodal approach which ought to be customized with the goal that it changes from individual to individual. When all is said in done, DM is arranged into two classifications: type 1 and type 2. In sort 1 diabetes (T1DM), chemical insulin isn`t created because of the obliteration of pancreatic β cells, while type 2 diabetes (T2DM) is portrayed by a reformist debilitation of insulin emission by pancreatic β cells and by a general diminished affectability of target tissues to the activity of this chemical. T2DM prompts other neurotic outcomes like cardiovascular issues, nephropathy, neuropathies and the patient gets inclined to various contaminations as well. The expanding clinical weight on patients with diabetes-related complexities additionally brings about a colossal monetary weight, which could seriously weaken worldwide financial development soon7-10.

The treatment of diabetes mellitus depends on insulin, diet alteration and oral hypoglycemic agent. Natural medication has created as an option for the treatment of diabetes since oral hypoglycemic specialists are costly and labeled with a few results (sickness, skin responses, liver infection, cardiovascular breakdown loose bowels, and so forth) Indian customary medical care framework utilizes various therapeutic plants customarily more than 1000 years in natural arrangements. Restorative plants, minerals and natural issue cover a significant piece of customary medications. The greater part of the Indian conventional clinical agents figures and administer their own plans. 21,000 plants are recorded by the WHO, which are utilized for therapeutic purposes far and wide. Among these, 2500 species are in India, out of which, 150 species are utilized industrially on a genuinely huge scope. India is the biggest maker of restorative spices and is known as the greenhouse of the world11,12. The researchers conducted preclinical antidiabetic activity of different medicinal plants. The aim of this review article is to collect data of reported antidiabetic medicinal plant and illustrate their mechanism of action and phytochemistry.

2 Plants having antidiabetic activity

Currently, some restorative plants have been accounted for to be helpful in diabetes worldwide and have been utilized experimentally as antidiabetic and antihyperlipidemic cures. The medicinal plant demonstrated antidiabetic activity by decreasing the glucose -6 phosphates and fructose 1, 6 phosphatase enzymes activity, enhancing the secretion of insulin, regeneration of pancreatic β cells, inhibiting the α-glucosidase and amylase etc mechanism. It has been reported that more than 400 plant species having hypoglycemic action have been accessible in writing, notwithstanding, looking for new antidiabetic drugs from normal plants is as yet alluring in light of the fact that they contain substances which show option and safe impacts on diabetes mellitus13. Table 1 illustrated the scientifically reported antidiabetic plants with their possible mechanism of action along with phytochemicals.

3 Phytochemicals having antidiabetic activity

The detection of novel herbal antidiabetic drugs have great importance due to their minimum side effects and safety concerns. In this connection, the examination of phytochemicals answerable for antidiabetic impacts has advanced over the most recent couple of many years. The antidiabetic impact of plant materials have been credited to the combination of phytochemicals or a solitary part of plant extract. Restorative plants produce a wide assortment of phytochemicals, incorporate alkaloids, phenolic acids, flavonoids, glycosides, saponins, polysaccharides, stilbenes, and tannin, which are seriously explored for their antidiabetic impacts. Table 2 demonstrated the phytochemical obtained from the plants having antidiabetic activity.

Future prospects

The numerous researchers reported the potential of medicinal plants for the treatment of diabetes. The active constituents isolated from the medicinal plants are clinically proved for the treatment of diabetes. Yet, plenty of isolated compounds has been not clinically investigated and not formulated into dosage form. So, these are essential component for the search of new antidiabetic medicines. Further, researchers can also explore the bioactive components responsible for the antidiabetic activity from traditionally used plants. The chemist researchers have huge opportunities to characterize the active constituents by isolating from the plant extract having potent antidiabetic activity.

The plant extract or bioactive components have higher molecular weight which lowered the bioavailability of dosage form. The researchers working in the nano and targeted drug delivery system can formulate the plant extract or active constituents in novel form and improve their bioavailability. The many plant substances are still require to explore their toxicity profile for the safety concern of the drug.    

Conclusion

Diabetes is one of the common endocrine disorders and widespread across the Globe. The Alternative system of medicines mentioned the plenty of medicinal plants for the treatment of diabetes. This review paper highlighted the mechanism of action of plant-based antidiabetic drug. Similarly, the mode of action of antidiabetic activity of the phytochemicals such as   alkaloids, flavonoids, triterpenoids, phenolic acids, tannins etc. It is looking forward to offering the essential data to the researchers pursuing research work in the field of pharmacology and therapeutics to develop herbal antidiabetic drugs.    

Conflicts of interest

None

Author’s contributions

SKJ and DPC equally participated in the preparation of manuscript. Both authors approve the publication of manuscript. 

References

  1. Idm’hand E, Msanda F, Cherifi K. Ethnopharmacological review of medicinal plants used to manage diabetes in Morocco. Clin Phytosci. 2020; 6: 18.
  2. Barkaoui M, Katiri A, Boubaker H, Msanda F. Ethnobotanical survey of medicinal plants used in the traditional treatment of diabetes in Chtouka Ait Baha and Tiznit (Western anti-atlas), Morocco. J Ethnopharmacol. 2017;198:338–50.
  3. Giovannini P, Howes M-JR, Edwards SE. Medicinal plants used in the traditional management of diabetes and its sequelae in Central America: a review. J Ethnopharmacol. 2016;184:58–71.
  4. Yagi SM, Yagi AI. Traditional medicinal plants used for the treatment of diabetes in the Sudan: a review. Afr J Pharm Pharmacol. 2018;12(3):27–40.
  5. Rahati S, Shahraki M, Arjomand G, Shahraki T. Food pattern, lifestyle and diabetes mellitus. Int J High Risk Behav Addict. 2014; 3(1): 8725.
  6. Nazarian-Samani Z, Sewell RD, Lorigooini Z, Rafieian-Kopaei M. Medicinal plants with multiple effects on diabetes mellitus and its complications: a systematic review. Curr Diab Rep. 2018; 18(10): 72.
  7. Bharti SK, Krishnan S, Kumar A, Kumar A. Antidiabetic phytoconstituents and their mode of action on metabolic pathways. Ther Adv Endocrinol Metab. 2018; 9(3): 81–100.
  8. Kumar A, Bharti SK, Kumar A. Therapeutic molecules against type 2 diabetes: what we have and what are we expecting? Pharmacol Rep. 2017; 69: 959–970.
  9. Kumar A, Bharti SK, Kumar A. Type 2 diabetes mellitus: the concerned complications and target organs. Apollo Med. 2014; 11: 161–166.
  10. Bharti SK, Krishnan S, Gupta AK. Herbal formulation to combat type 2 diabetes mellitus. Germany: LAMBERT Academic Publishing, 2013.
  11. Kayarohanam S, Kavimani S. Current Trends of Plants Having Antidiabetic Activity: A Review. J Bioanal Biomed. 2015; 7: 055-065.
  12. Kar A, Choudhary BK, Bandyopadhyay NG. Comparative evaluation of hypoglycaemic activity of some Indian medicinal plants in alloxan diabetic rats. J Ethnopharmacol. 2003; 84: 105-108.
  13. Malviya N, Jain S, Malviya S. Antidiabetic Potential of Medicinal Plants. Acta Poloniae Pharmaceutica ñ Drug Research. 2010; 67(2): 113-118.
  14. Jianfang F, Jufang F, Jun Y, Nanyan Z, Bin G. Anti-Diabetic  activities of Acanthopanax senticosus polysaccharide (ASP) in combination  with metformin. International Journal of Biological Macromolecules. 2012; 50: 619-  623. 
  15. Prisilla DH, Balamurugan R, Shah HR. Antidiabetic activity of methanol  extract of Acorus calamus in STZ induced diabetic rats. Asian Pacific Journal  of Tropical Biomedicine. 2012; 2: 941-946. 
  16. Prashant C, Bharat G, Ashoke KG. Antidiabetic activity of Adina cordifolia  (Roxb) leaves in alloxan induced diabetic rats. Asian Pacific Journal of Tropical  Biomedicine. 2012; 2: 1630-1632. 
  17. Oyedemi SO, Adewusi EA, Aiyegoro OA, Akinpelu DA. Antidiabetic   and haematological effect of aqueous extract of stem bark of Afzelia africana   (Smith) on streptozotocin-induced diabetic Wistar rats. Asian Pac J Trop   Biomed. 2011; 1: 353-358.  
  18. Naskar S, Mazumder UK, Pramanik G, Gupta M, Kumar RB. Evaluation of antihyperglycemic activity of Cocos nucifera Linn. on   streptozotocin induced type 2 diabetic rats. J Ethnopharmacol. 2011; 138: 769-773.  
  19. Naquvi KJ, Ali M, Ahmad J. Antidiabetic activity of aqueous extract of Coriandrum sativum L. fruits in streptozotocin induced rats. Indian J Exp Biol. 2004;42(9):909–12.
  20. Mohajeri D, Mousavi G, Doustar Y. Antihyperglycemic and pancreasprotective effects of Crocus sativus L.(saffron) stigma ethanolic extract on rats with alloxan-induced diabetes. J Biol Sci. 2009; 9(4): 302–10.
  21. Pinto MDS, Kwon YI, Apostolidis E. Potential of Ginkgo biloba L. leaves in the management of hyperglycemia and hypertension using in vitro models. Bioresour Technol. 2009; 100: 6599–6609.
  22. Sugihara Y, Nojima H, Matsuda H. Antihyperglycemic effects of gymnemic acid IV, a compound derived from Gymnema sylvestre leaves in streptozotocin-diabetic mice. J Asian Nat Prod Res. 2000; 2: 321–327.
  23. El-Beshbishy H, Bahashwan S. Hypoglycemic effect of basil (Ocimum basilicum) aqueous extract is mediated through inhibition of α-glucosidase and α-amylase activities: an in vitro study. Toxicol Ind Health. 2012;28(1):42–50.
  24. Van de, Venter M, Roux S, Bungu LC. Antidiabetic screening and scoring of 11 plants traditionally used in South Africa. J Ethnopharmacol. 2008; 119: 81–86.
  25. Ali H, Houghton PJ, Soumyanath A. α-Amylase inhibitory activity of some Malaysian plants used to treat diabetes; with particular reference to Phyllanthus amarus. J Ethnopharmacol. 2006; 107: 449–455.
  26. Eidi A, Eidi M. Antidiabetic effects of sage (Salvia officinalis L.) leaves in normal and streptozotocin-induced diabetic rats. Diabetes Metab Syndr. 2009; 3(1):40–4.
  27. Nandini CD, Sambaiah K, Salimath PV. Dietary fibres ameliorate decreased synthesis of heparan sulphate in streptozotocin induced diabetic rats. J Nutr Biochem. 2003; 14: 203–210
  28. Singab ANB, El-Beshbishy HA, Yonekawa M, Nomura T, Fukai T. Hypoglycemic effect of Egyptian Morus alba root bark extract: effect on diabetes and lipid peroxidation of streptozotocin-induced diabetic rats. J Ethnopharmacol. 2005;100(3):333–8.
  29. Noor H, Ashcroft SJH. Insulinotropic activity of Tinospora crispa extract: effect on β-cell Ca2+ handling. Phytother Res. 1998; 12: 98–102. 
  30. Kazeem MI, Ogungbe SM, Saibu GM, Aboyade OM. In vitro study on the hypoglycemic potential of Nicotiana tabacum leaf extracts. Bangl J Pharmacol. 2014;9(2):140–5.
  31. Şendoğdu N, Aslan M, Orhan DD, Ergun F, Yeşilada E. Antidiabetic and antioxidant effects of Vitis vinifera L. leaves in streptozotocin-diabetic rats. Turkish J Pharm Sci. 2006; 3(1): 7–18.
  32. Al-Amin ZM, Thomson M, Al-Qattan KK, Peltonen-Shalaby R, Ali M. Antidiabetic and hypolipidaemic properties of ginger (Zingiber officinale) in streptozotocin-induced diabetic rats. Br J Nutr. 2006;96(4):660–6.
  33. Alimohammadi S, Hobbenaghi R, Javanbakht J, Kheradmand D, Mortezaee R, Tavakoli M. Protective and antidiabetic effects of extract from Nigella sativa on blood glucose concentrations against streptozotocin (STZ)- induced diabetic in rats: an experimental study with histopathological evaluation. Diagn Pathol. 2013; 8(1):137.
  34. Vuksan V, Sievenpiper JL, Koo VY. American ginseng (Panax quinquefolius L) reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus. Arch Intern Med. 2000; 160: 1009–1013. 
  35. Howes JB, Tran D, Brillante D. Effects of dietary supplementation with isoflavones from red clover on ambulatory blood pressure and endothelial function in postmenopausal type 2 diabetes. Diabetes Obes Metab. 2003; 5: 325–332.
  36. Huseini HF, Larijani B, Heshmat R. The efficacy of Silybum marianum (L.) Gaertn (Silymarin) in the treatment of type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2006; 20: 1036–1039.
  37. Ananthi J, Prakasam A, Pugalendi KV. Antihyperglycemic activity of Eclipta alba leaf on alloxan-induced diabetic rats. Yale J Biol Med. 2003; 76: 97–102
  38. Al masri IM, Mohammad MK, Tahaa MO. Inhibition of dipeptidyl peptidase IV (DPP-IV) is one of the mechanisms explaining the hypoglycemic effect of berberine. J Enzyme Inhib Med Chem. 2009; 24: 1061–1066. 
  39. Akhtar MS. Hypoglycaemic activities of some indigenous medicinal plants traditionally used as antidiabetic drugs. J Pak Med Assoc. 1992; 42: 271–277.
  40. Oboh G, Ademosun A. Phenolic extracts from grapefruit peels (Citrus paradisi) inhibit key enzymes linked with type 2 diabetes and hypertension. J Food Biochem. 2011; 35(6): 1703–9.
  41. Pan GY, Huang ZJ, Wang GJ, Fawcett JP, Liu XD, Zhao XC, Sun JG, Xie YY. The antihyperglycaemic activity of berberine arises from a decrease of glucose absorption. Planta Med. 2003; 69: 632–636. 
  42. Gaikwad SB, Mohan GK, Rani MS. Phytochemicals for diabetes management. Pharm. Crop. 2014;5:11–28.
  43. Lau YS, Tian XY, Mustafa MR, Murugan D. Boldine improves endothelial function in diabetic db/db mice through inhibition of angiotensin II-mediated BMP4oxidative stress cascade. Br. J. Pharmacol. 2013;170:1190–1198.
  44. Wiedemann M, Gurrola-Díaz C, Vargas-Guerrero B, Wink M, García-López P, Düfer M. Lupanine improves glucose homeostasis by influencing KATP channels and insulin gene expression. Molecules. 2015; 20: 19085–19100.
  45. Li G, Xu H, Zhu S, Xu W, Qin S, Liu S, Tu G, Peng H, Qiu S, Yu S. Effects of neferine on CCL5 and CCR5 expression in SCG of type 2 diabetic rats. Brain Res. Bull. 2013; 90: 79–87.
  46. Guo C, Han F, Zhang C, Xiao W, Yang Z. Protective effects of oxymatrine on experimental diabetic nephropathy. Planta Med. 2014; 80: 269–276.
  47. Den Hartogh DJ, Tsiani E. Antidiabetic properties of naringenin: A citrus fruit polyphenol. Biomolecules. 2019; 9: 99.
  48. Mackenzie T, Leary L, Brooks WB. The effect of an extract of green and black tea on glucose control in adults with type 2 diabetes mellitus: Double-blind randomized study. Metabolism. 2007; 56: 1340–1344.
  49. Prasath GS, Pillai SI, Subramanian SP. Fisetin improves glucose homeostasis through the inhibition of gluconeogenic enzymes in hepatic tissues of streptozotocin induced diabetic rats. Eur. J. Pharmacol. 2014; 740: 248–254.
  50. Prasath GS, Subramanian SP. Antihyperlipidemic effect of fisetin, a bioflavonoid of strawberries, studied in streptozotocin-induced diabetic rats. J. Biochem. Mol. Toxicol. 2014; 28. 
  51. Alkhalidy H, Moore W, Zhang Y, McMillan R, Wang A, Ali M, Suh KS, Zhen W, Cheng Z, Jia Z. Small molecule kaempferol promotes insulin sensitivity and preserved pancreatic b-cell mass in middle-aged obese diabetic mice. J. Diabetes Res. 2015; 2015:532984.
  52. Wang G, Li W, Lu X, Bao P, Zhao X. Luteolin ameliorates cardiac failure in type I diabetic cardiomyopathy. J. Diabetes Its Complicat. 2012;26:259–265.
  53. Tsai SJ, Huang CS, Mong MC, Kam WY, Huang HY, Yin MC. Anti-inflammatory and antifibrotic effects of naringenin in diabetic mice. J. Agric. Food Chem. 2012; 60:514–521.
  54. Tang DQ, Wei YQ, Yin XX, Lu Q, Hao HH, Zhai YP, Wang JY, Ren J. In vitro suppression of quercetin on hypertrophy and extracellular matrix accumulation in rat glomerular mesangial cells cultured by high glucose. Fitoterapia. 2011; 82: 920–926.
  55. Prince P, Kamalakkannan N. Rutin improves glucose homeostasis in streptozotocin diabetic tissues by altering glycolytic and gluconeogenic enzymes. J. Biochem. Mol. Toxicol. 2006; 20: 96–102.
  56. Kappel VD, Cazarolli LH, Pereira DF, Postal BG, Zamoner A, Reginatto FH, Silva FRMB. Involvement of GLUT-4 in the stimulatory effect of rutin on glucose uptake in rat soleus muscle. J. Pharm. Pharmacol. 2013;65:1179–1186.
  57. Hsu CY, Shih HY, Chia YC, Lee CH, Ashida H, Lai YK, Weng CF. Rutin potentiates insulin receptor kinase to enhance insulin-dependent glucose transporter 4 translocation. Mol. Nutr. Food Res. 2014;58:1168–1176.
  58. Paoli P, Cirri P, Caselli A, Ranaldi F, Bruschi G, Santi A, Camici G. The insulin-mimetic effect of morin: A promising molecule in diabetes treatment. Biochim. Biophys. Acta. 2013;1830:3102–3111.
  59. Taguchi K, Hida M, Hasegawa M, Matsumoto T, Kobayashi T. Dietary polyphenol morin rescues endothelial dysfunction in a diabetic mouse model by activating the AKT/ENOS pathway. Mol. Nutr. Food Res. 2016;60:580–588.
  60. Razavi T, Kouhsari SM, Abnous K. Morin exerts anti-diabetic effects in human HEPG2 cells via down-regulation of miR-29a. Exp. Clin. Endocrinol. Diabetes. 2018.
  61. Meng S, Yang F, Wang Y, Qin Y, Xian H, Che H, Wang L. Silymarin ameliorates diabetic cardiomyopathy via inhibiting TGF-β1/smad signaling. Cell Biol. Int. 2019; 43: 65–72.
  62. Amjid A, Ajaz AG, Mohd M, Siddiqui WA. Chrysin, an antiinflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats. Toxicol. Appl. Pharm. 2014; 279:1–7.
  63. Ammon HPT. Use of Boswellic Acids for the Prophylaxis and/or Treatment of Damage to and/or Inflammation of the Islets of Langerhans. 8975228B2. U.S. Patent. 2015 Mar 10.
  64. Jadhav R, Puchchakala G. Hypoglycemic and antidiabetic activity of flavonoids: Boswellic acid, ellagic acid, quercetin, rutin on streptozotocin-nicotamide induced type 2 diabetic rats. Int. J. Pharmcy Pharm. Sci. 2011;4:251–256. 
  65. Kim JE, Lee MH, Nam DH. Celastrol, an nf-κB inhibitor, improves insulin resistance and attenuates renal injury in db/db mice. PLoS ONE. 2013;8: 62068.
  66. Wang C, Shi C, Yang X, Yang M, Sun H, Wang C. Celastrol suppresses obesity process via increasing antioxidant capacity and improving lipid metabolism. Eur. J. Pharmacol. 2015; 744: 52–58.
  67. Zeng XY, Wang YP, Cantley J, Iseli TJ, Molero JC, Hegarty BD, Kraegen EW, Ye Y, Ye JM. Oleanolic acid reduces hyperglycemia beyond treatment period with Akt/FoxO1-induced suppression of hepatic gluconeogenesis in type-2 diabetic mice. PLoS ONE. 2012;7:e42115.
  68. Huang SH, Lin GJ, Chu CH, Yu JC, Chen TW, Chen YW, Chien MW, Chu CC, Sytwu HK. Triptolide ameliorates autoimmune diabetes and prolongs islet graft survival in nonobese diabetic mice. Pancreas. 2013;42:442–451.
  69. Jenkins DJ, Goff DV, Leeds AR, Alberti KG, Wolever TM, Gassull MA, Hockaday TD. Unabsorbable carbohydrates and diabetes: Decreased postprandial hyperglycaemia. Lancet. 1976; 2:172–177.
  70. Doi K, Matsuura M, Kawara A, Baba S. Treatment of diabetes with glucomannan (konjac mannan) Lancet. 1979;1:987–988.
  71. Minakawa M, Miura Y, Yagasaki K. Piceatannol, a resveratrol derivative, promotes glucose uptake through glucose transporter 4 translocation to plasma membrane in l6 myocytes and suppresses blood glucose levels in type 2 diabetic model db/db mice. Biochem. Biophys. Res. Commun. 2012; 422:469–475.
  72. Benzler J, Ganjam GK, Pretz D, Oelkrug R, Koch CE, Legler K, Stöhr S, Culmsee C, Williams LM, Tups A. Central inhibition of ikkβ/nf-κb signaling attenuates high-fat diet–induced obesity and glucose intolerance. Diabetes. 2015; 64: 2015–2027.
  73. Naik SR, Niture NT, Ansari AA, Shah PD. Anti-diabetic activity of embelin: Involvement of cellular inflammatory mediators, oxidative stress and other biomarkers. Phytomedicine. 2013; 20: 797–804.
  74. Durg S, Veerapur VP, Neelima S, Dhadde SB. Antidiabetic activity of Embelia ribes, embelin and its derivatives: A systematic review and meta-analysis. Biomed. Pharmacother. 2017; 86: 195–204.
  75. Yu Z, Zhang T, Gong C, Sheng Y, Lu B, Zhou L, Ji L, Wang Z. Erianin inhibits high glucose-induced retinal angiogenesis via blocking erk1/2-regulated hif-1α-vegf/vegfr2 signaling pathway. Sci. Rep. 2016; 6: 34306.
  76. Cui J, Gong R, Hu S, Cai L, Chen L. Gambogic acid ameliorates diabetes-induced proliferative retinopathy through inhibition of the hif-1α/vegf expression via targeting pi3k/akt pathway. Life Sci. 2018; 192: 293–303.
  77. Madhuri K, Naik PR. Modulatory effect of garcinol in streptozotocin-induced diabetic wistar rats. Arch. Physiol. Biochem. 2017; 123: 322–329.
  78. Mali KK, Dias RJ, Havaldar VD, Yadav SJ. Antidiabetic effect of garcinol on streptozotocin-induced diabetic rats. Indian J. Pharm. Sci. 2017;79:463–468.
  79. Sun J, Fu X, Liu Y, Wang Y, Huo B, Guo Y, Gao X, Li W, Hu X. Hypoglycemic effect and mechanism of honokiol on type 2 diabetic mice. Drug Des. Devel. Ther. 2015; 9: 6327–6342.