J Appl Biomed 17:190-197, 2019 | DOI: 10.32725/jab.2019.013

Beneficial effects of Stevioside on AGEs, blood glucose, lipid profile and renal status in streptozotocin-induced diabetic rats

Urmila Aswar1,*, Vinayak Gogawale2, Pankaj Miniyar2, Yugendra Patil3
1 Bharati Vidyapeeth (Deemed to be University), Poona College of Pharmacy, Erandwane, Pune, Maharashtra, India
2 STES's Sinhgad Institute of Pharmacy, Savitribai Phule Pune University, Narhe, Pune, Maharashtra, India
3 National Chemical Laboratory, Pune, Maharashtra, India

The advanced glycated end products (AGEs) are formed in the diabetic patients; it is a major cause of macrovascular and microvascular complications in diabetes. Clinically there is no treatment available for the AGEs. Stveoside (Stv), a sweetener has potent anti-diabetic and anti-oxidant activity. Hence, we investigated its use in prevention of AGEs formation using in vitro and in vivo models. Diabetes was induced by streptozotocin (STZ). These rats were kept without treatment till blood HbA1c was markedly increased. They were then divided into 5 groups and treated orally with vehicle or Metformin (MET) or Stv respectively for 28 days. Every 7th day, animals were tested for body weight and blood glucose (BG). On the last day of treatment, all the groups were evaluated for physiological and biochemical parameters, histopathology and AGEs; N-carboxymethyl-lysine (CML) estimation. Stv showed inhibition of AGEs in in vitro as well as in in vivo respectively. Positive effects were seen on the BG, lipid profile and urine parameters as well it showed reduced formation of CML. It also showed antihyperglycaemic, antihyperlipedemic and nephroprotective activities. The present study provides scientific rationale for the use of Stv as a sweetener with additional benefits in diabetes.

Keywords: AGEs; Diabetes; Diabetes complications; N-carboxymethyl-lysine; Stevioside; Streptozotocin
Grants and funding:

The authors would like to acknowledge BCUD, SPPU, Pune for funding the project. We would like to thank Prof. M. N. Navale, Founder, STES, Dr. K. G. Bothara, Principal, SIOP for providing the necessary facilities to carry out the preclinical research work and Dr. Mahesh Kulkarni, Scientist, Proteomics Facility Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune, for helping us to perform western blot studies.

Conflicts of interest:

The authors declare that there are no conflict of interests.

Received: October 16, 2018; Accepted: June 24, 2019; Prepublished online: August 21, 2019; Published: September 18, 2019  Show citation

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Aswar U, Gogawale V, Miniyar P, Patil Y. Beneficial effects of Stevioside on AGEs, blood glucose, lipid profile and renal status in streptozotocin-induced diabetic rats. J Appl Biomed. 2019;17(3):190-197. doi: 10.32725/jab.2019.013. PubMed PMID: 34907701.
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    References

    1. Baynes JW (1991). Role of oxidative stress in development of complications in diabetes. Diabetes 40(4): 405-412. DOI: 10.2337/diab.40.4.405. Go to original source... Go to PubMed...
    2. Bhonsle HS, Korwar,AM, Kote SS, Golegaonkar SB, Chougale AD, Shaik ML, et al. (2012). Low plasma albumin levels are associated with increased plasma protein glycation and HbA1c in diabetes. J Proteome Res 11(2): 1391-1396. DOI: 10.1021/pr201030m. Go to original source... Go to PubMed...
    3. Bohlender JM, Franke S, Stein G, Wolf G (2005). Advanced glycation end products and the kidney. Am J Physiol Renal Physiol 289(4): F645-F659. DOI: 10.1152/ajprenal.00398.2004. Go to original source... Go to PubMed...
    4. Boonkaewwan C, Ao M, Toskulkao C, Rao MC (2008). Specific immunomodulatory and secretory activities of stevioside and steviol in intestinal cells. J Agric Food Chem 56(10): 3777-3784. DOI: 10.1021/jf072681o. Go to original source... Go to PubMed...
    5. Brownlee M (1995). Advanced protein glycosylation in diabetes and aging. Annu Rev Med 46(1): 223-234. DOI: 10.1146/annurev.med.46.1.223. Go to original source... Go to PubMed...
    6. Carr MC, Brunzell JD (2004). Abdominal obesity and dyslipidemia in the metabolic syndrome: importance of type 2 diabetes and familial combined hyperlipidemia in coronary artery disease risk. The J Clin Endocrinol Metab 89(6): 2601-2607. DOI:10.1210/jc.2004-0432. Go to original source... Go to PubMed...
    7. Chang PC, Tsai SC, Chong LY, Kao MJ (2014). N-Phenacylthiazolium bromide inhibits the advanced glycation end product (AGE)-AGE receptor axis to modulate experimental periodontitis in rats. J Periodontol 85(7): e268-e276. DOI: 10.1902/jop.2014.130554. Go to original source... Go to PubMed...
    8. Daroux M, Prevost G, Maillard-Lefebvre H, Gaxatte C, D'Agati V, et al. (2010). Advanced glycation end-products: implications for diabetic and non-diabetic nephropathies. Diabetes Metab 36(1): 1-10. DOI:10.1016/j.diabet.2009.06.005. Go to original source... Go to PubMed...
    9. Elbe H, Vardi N, Orman D, Taºlidere E, Yildiz A (2014). Ameliorative effects of aminoguanidine on rat aorta in Streptozotocin-induced diabetes and evaluation of α-SMA expression. Anatol J Cardiol 14(8): 679-684. DOI:10.5152/akd.2014.5047. Go to original source... Go to PubMed...
    10. Elosta A, Ghous T, Ahmed N (2012). Natural products as anti-glycation agents: possible therapeutic potential for diabetic complications. Curr Diabetes Rev 8(2): 92-108. DOI: 10.2174/157339912799424528. Go to original source... Go to PubMed...
    11. Figarola J, Scott S, Loera S, Tessler C, Chu P, Weiss L, Hardy J, Rahbar S (2003). LR-90 a new advanced glycation endproduct inhibitor prevents progression of diabetic nephropathy in streptozotocin-diabetic rats. Diabetologia 46(8): 1140-1152. DOI: 10.1007/s00125-003-1162-70. Go to original source...
    12. Freedman BI, Wuerth JP, Cartwright K, Bain RP, Dippe S, Hershon K, et al. (1999). Design and baseline characteristics for the aminoguanidine Clinical Trial in Overt Type 2 Diabetic Nephropathy (ACTION II). Control Clin Trials 20(5): 493-510. DOI: 10.1016/S0197-2456(99)00024-0. Go to original source... Go to PubMed...
    13. Friedman EA (1999). Advanced glycosylated end products and hyperglycemia in the pathogenesis of diabetic complications. Diabetes Care 22(Suppl. 2): B65-B71.
    14. Gardana C, Simonetti P, Canzi E, Zanchi R, Pietta P (2003). Metabolism of stevioside and rebaudioside A from Stevia rebaudiana extracts by human microflora. J Agric Food Chem 51(22): 6618-6622. DOI: 10.1021/jf0303619. Go to original source... Go to PubMed...
    15. Geeraert B, Crombe F, Hulsmans M, Benhabiles N, Geuns J, Holvoet P (2010). Stevioside inhibits atherosclerosis by improving insulin signaling and antioxidant defense in obese insulin-resistant mice. Int J Obesity 34(3): 569-577. DOI: 10.1038/ijo.2009.261. Go to original source... Go to PubMed...
    16. Goh SY, Cooper ME (2008). The role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab 93(4): 1143-1152. DOI: 10.1210/jc.2007-1817. Go to original source... Go to PubMed...
    17. Gregersen S, Jeppesen PB, Holst JJ, Hermansen K (2004). Antihyperglycemic effects of stevioside in type 2 diabetic subjects. Metabolism 53(1): 73-76. DOI: 10.1016/j.metabol.2003.07.013. Go to original source... Go to PubMed...
    18. Hammes HP, Brownlee M, Lin J, Schleicher E, Bretzel R (1999). Diabetic retinopathy risk correlates with intracellular concentrations of the glycoxidation product Ne-(carboxymethyl) lysine independently of glycohaemoglobin concentrations. Diabetologia 42(5): 603-607. DOI: 10.1007/s001250051201. Go to original source... Go to PubMed...
    19. Hsieh MH, Chan P, Sue YM, Liu JC, Liang TH, Huang TY, et al. (2003). Efficacy and tolerability of oral stevioside in patients with mild essential hypertension: a two-year, randomized, placebo-controlled study. Clin Ther 25(11): 2797-2808. DOI: 10.1016/S0149-2918(03)80334-X. Go to original source... Go to PubMed...
    20. Jakus V, Rietbrock N (2004). Advanced glycation end-products and the progress of diabetic vascular complications. Physiol Res 53(2): 131-142. Go to original source...
    21. Jeppesen PB, Gregersen S, Alstrup K, Hermansen K (2002). Stevioside induces antihyperglycaemic, insulinotropic and glucagonostatic effects in vivo: studies in the diabetic Goto-Kakizaki (GK) rats. Phytomedicine 9(1): 9-14. DOI: 10.1078/0944-7113-00081. Go to original source... Go to PubMed...
    22. Jeppesen PB, Gregersen S, Poulsen C, Hermansen K (2000). Stevioside acts directly on pancreatic β cells to secrete insulin: Actions independent of cyclic adenosine monophosphate and adenosine triphosphate - sensitivie K+-channel activity. Metabolism 49(2): 208-214. DOI: 10.1016/S0026-0495(00)91325-8. Go to original source... Go to PubMed...
    23. Jeppesen PB, Gregersen S, Rolfse S, Jepsen M, Colombo M, Agger A, et al. (2003). Antihyperglycemic and blood pressure-reducing effects of stevioside in the diabetic Goto-Kakizaki rat. Metabolism 52(3): 372-378. DOI: 10.1053/meta.2003.50058. Go to original source... Go to PubMed...
    24. Kannel WB, McGee DL (1979). Diabetes and cardiovascular disease: the Framingham study. Jama 241 (19): 2035-2038. DOI: 10.1001/jama.1979.03290450033020. Go to original source... Go to PubMed...
    25. Liu JC, Kao PK, Chan P, Hsu YH, Hou CC, Lien GS, et al. (2003). Mechanism of the antihypertensive effect of stevioside in anesthetized dogs. Pharmacol 67(1): 14-20. DOI: 10.1159/000066782. Go to original source... Go to PubMed...
    26. Naowaboot J, Pannangpetch P, Kukongviriyapan V, Kongyingyoes B, Kukongviriyapan U (2009). Antihyperglycemic, antioxidant and antiglycation activities of mulberry leaf extract in streptozotocin-induced chronic diabetic rats. Plant Food Hum Nutr 64(2): B116-B121. DOI: 10.1007/s11130-009-0112-5. Go to original source... Go to PubMed...
    27. O'Seaghdha CM, Hwang SJ, Ho JE, Vasan RS, Levy D, Fox CS (2013). Elevated galectin-3 precedes the development of CKD. J Am Soc Nephrol 24(9): 1470-1477. DOI: 10.1681/ASN.2012090909. Go to original source... Go to PubMed...
    28. Peppa M, Uribarri J, Vlassara H (2008). Aging and glycoxidant stress. Hormones (Athens) 7(2): 123-132. DOI: 10.1007/BF03401503. Go to original source... Go to PubMed...
    29. Pinhas-Hamiel O, Levek-Motola N, Kaidar K, Boyko V, Tisch E, Mazor-Aronovitch K, et al. (2015). Prevalence of overweight, obesity and metabolic syndrome components in children, adolescents and young adults with type 1 diabetes mellitus. Diabetes Metab Res Rev 31(1): 76-84. DOI: 10.1002/dmrr.2565. Go to original source... Go to PubMed...
    30. Rizzo B, Zambonin L, Angeloni C, Leoncini E, Vieceli Dalla Sega F, et al. (2013). Steviol glycosides modulate glucose transport in different cell types. Oxid Med Cell Longev 2013: 348169. DOI: 10.1155/2013/348169. Go to original source... Go to PubMed...
    31. Rodríguez-Mañas L, Angulo J, Peiró C, Llergo JL, Sánchez-Ferrer A, López-Dóriga P, Sánchez-Ferrer CF (1998). Endothelial dysfunction and metabolic control in streptozotocin-induced diabetic rats. Br J Pharmacol 123(8): 1495-1502. DOI: 10.1038/sj.bjp.0701749. Go to original source... Go to PubMed...
    32. Sajithlal G, Chithra P, Chandrakasan G (1998). Effect of curcumin on the advanced glycation and cross-linking of collagen in diabetic rats. Biochem Pharmacol 56(12): 1607-1614. DOI: 10.1016/S0006-2952(98)00237-8. Go to original source... Go to PubMed...
    33. Saltiel AR, Kahn CR (2001). Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414(6865): 799-806. DOI: 10.1038/414799a. Go to original source... Go to PubMed...
    34. Schalkwijk CG, Baidoshvili A, Stehouwer CD, van Hinsbergh VW, Niessen HW (2004). Increased accumulation of the glycoxidation product N ε-(carboxymethyl) lysine in hearts of diabetic patients: generation and characterisation of a monoclonal anti-CML antibody. Biochim Biophys Acta 1636(2-3): 82-89. DOI: 10.1016/j.bbalip.2003.07.002. Go to original source... Go to PubMed...
    35. Schleicher ED, Wagner E, Nerlich AG, (1997). Increased accumulation of the glycoxidation product N (epsilon)-(carboxymethyl) lysine in human tissues in diabetes and aging. J Clin Invest 99(3): 457-468. DOI: 10.1172/JCI119180. Go to original source... Go to PubMed...
    36. Sehar I, Kaul A, Bani S, Pal HC, Saxena AK (2008). Immune up regulatory response of a non-caloric natural sweetener, stevioside. Chem Biol Interact 173(2): 115-121. DOI: 10.1016/j.cbi.2008.01.008. Go to original source... Go to PubMed...
    37. Sharma V, Sharma P (2013). Role of different molecular pathways in the development of diabetes-induced nephropathy. J Diabetes Metab S9: 004. DOI: 10.4172/2155-6156.S9-004. Go to original source...
    38. Singh R, Barden A, Mori T, Beilin L (2001). Advanced glycation end-products: a review. Diabetologia 44(2):129-146. DOI: 10.1007/s001250051591. Go to original source... Go to PubMed...
    39. Stoyanova S, Geuns J, Hideg É, Van Den Ende W (2011). The food additives inulin and stevioside counteract oxidative stress. Int J Food Sci Tech 62(3): 207-214. DOI: 10.3109/09637486.2010.523416. Go to original source... Go to PubMed...
    40. Trinder P (1969). Determination of blood glucose using an oxidase-peroxidase system with a non-carcinogenic chromogen. J Clin Pathol 22(2): 158-161. DOI: 10.1136/jcp.22.2.158. Go to original source... Go to PubMed...
    41. Vlassara H, Uribarri J (2014). Advanced glycation end products (AGE) and diabetes: cause, effect, or both? Curr Diab Rep 14(1): 453. DOI: 10.1007/s11892-013-0453-1. Go to original source... Go to PubMed...
    42. (A)(B)(C)(D)Ansari NA, Ali R (2011). Glycated lysine residues: a marker for non-enzymatic protein glycation in age-related diseases. Dis Markers 30(6): 317-324. DOI: 10.3233/DMA-2011-0791. Go to original source... Go to PubMed...
    43. (A)(B)(C)(D)Ansari NA, Ali R (2011). Glycated lysine residues: a marker for non-enzymatic protein glycation in age-related diseases. Dis Markers 30(6): 317-324. DOI: 10.3233/DMA-2011-0791. Go to original source... Go to PubMed...

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