Sativoside Mitigates High-Fat Diet-Induced Inflammation and Type-2 Diabetes in Adipose Tissue of Wistar Rats

Download Article

DOI: 10.21522/TIJPH.2013.SE.23.01.Art002

Authors : Vishnu Priya Veeraraghavan, Rajesh Kumar K.S, Selvaraj Jayaraman

Abstract:

This study aimed to investigate the impact of Stevioside, on the biochemical changes in high-fat diet-fed Wistar rats. Adult male Wistar rats were induced into a diabetic state through the administration of a high-fat diet and sucrose for 60 days, followed by oral administration of stevioside (20 mg/kg/day) for 45 days. Various parameters, including fasting blood glucose, oral glucose tolerance, insulin, insulin tolerance, liver function (ALT, AST, ALP), kidney function (urea and creatinine), and lipid profiles (TC, TG, FFA, HDL-c and LDL-c), serum adipokines levels such as adiponectin, leptin, resistin were assessed. Stevioside treatment notably improved glucose and insulin tolerances in diabetic rats and normalized their elevated levels of fasting blood glucose, serum insulin, and lipid profile. In the high-fat diet-induced type 2 diabetes rat model, Stevioside effectively restored the altered blood serum levels, demonstrating efficacy comparable to that of metformin. Therefore, Stevioside displays promise as a potential phytomedicine for managing type 2 diabetes mellitus.
Keywords: High-fat diet, Insulin tolerance, Type-2 diabetes, Stevia rebaudiana.

References:

[1] Farag YM, Gaballa MR. Diabesity: an overview of a rising epidemic. Nephrol Dial Transplant. 2011 Jan;26(1):28-35. doi: 10.1093/ndt/gfq576. Epub 2010 Nov 2. PMID: 21045078.

[2] Xu G, Liu B, Sun Y, Du Y, Snetselaar LG, Hu FB, Bao W. Prevalence of diagnosed type 1 and type 2 diabetes among US adults in 2016 and 2017: population based study. BMJ. 2018 Sep 4;362:k1497. doi: 10.1136/bmj.k1497. PMID: 30181166; PMCID: PMC6122253.

[3] Prasad M, Rajagopal P, Devarajan N, Veeraraghavan VP, Palanisamy CP, Cui B, Patil S, Jayaraman S. A comprehensive review on high -fat diet-induced diabetes mellitus: an epigenetic view. J Nutr Biochem. 2022 Sep;107:109037. doi: 10.1016/j.jnutbio.2022.109037. Epub 2022 May 6. PMID: 35533900.

[4] Prasad M, Jayaraman S, Natarajan SR, Veeraraghavan VP, Krishnamoorthy R, Gatasheh MK, Palanisamy CP, Elrobh M. Piperine modulates IR/Akt/GLUT4 pathways to mitigate insulin resistance: Evidence from animal and computational studies. Int J Biol Macromol. 2023 Dec 31;253(Pt 5):127242. doi: 10.1016/j.ijbiomac.2023.127242. Epub 2023 Oct 4. PMID: 37797864.

[5] Kiruthigha T, Gayathri R, Vishnu Priya V, Selvaraj J, Kavitha, S. Piperine Modulates High Fat Diet - Induced Renal Damage by Regulating Kim-1 and Igf-1 Beta Signaling Molecules in Male Wistar Rats”. J. Adv. Zool. 2023 44 (S5):246-54.

[6] Zhang P, Zhang X, Brown J, Vistisen D, Sicree R, Shaw J, Nichols G. Global healthcare expenditure on diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010 Mar;87(3):293-301. doi: 10.1016/j.diabres.2010.01.026. Epub 2010 Feb 19. Erratum in: Diabetes Res Clin Pract. 2011 May;92(2):301. PMID: 20171754.

[7] Lozano I, Van der Werf R, Bietiger W, Seyfritz E, Peronet C, Pinget M, Jeandidier N, Maillard E, Marchioni E, Sigrist S, Dal S. High-fructose and high-fat diet-induced disorders in rats: impact on diabetes risk, hepatic and vascular complications. Nutr Metab (Lond). 2016 Feb 25;13:15. doi: 10.1186/s12986-016-0074-1. PMID: 26918024; PMCID: PMC4766713.

[8] Goyal SK, Samsher, Goyal RK. Stevia (Stevia rebaudiana) a bio-sweetener: a review. Int J Food Sci Nutr. 2010 Feb;61(1):1-10. doi: 10.3109/09637480903193049. PMID: 19961353.

[9] Samuel P, Ayoob KT, Magnuson BA, Wölwer-Rieck U, Jeppesen PB, Rogers PJ, Rowland I, Mathews R. Stevia Leaf to Stevia Sweetener: Exploring Its Science, Benefits, and Future Potential. J Nutr. 2018 Jul 1;148(7):1186S-1205S. doi: 10.1093/jn/nxy102. PMID: 29982648.

[10] Orellana-Paucar AM. Steviol Glycosides from Stevia rebaudiana: An Updated Overview of Their Sweetening Activity, Pharmacological Properties, and Safety Aspects. Molecules. 2023 Jan 27;28(3):1258. doi: 10.3390/molecules28031258. PMID: 36770924; PMCID: PMC9920402.

[11] Barriocanal LA, Palacios M, Benitez G, Benitez S, Jimenez JT, Jimenez N, Rojas V. Apparent lack of pharmacological effect of steviol glycosides used as sweeteners in humans. A pilot study of repeated exposures in some normotensive and hypotensive individuals and in Type 1 and Type 2 diabetics. Regul Toxicol Pharmacol. 2008 Jun;51(1):37-41. doi: 10.1016/j.yrtph.2008.02.006. Epub 2008 Mar 5. PMID: 18397817.

[12] Carrera-Lanestosa A, Moguel-Ordóñez Y, Segura-Campos M. Stevia rebaudiana Bertoni: A Natural Alternative for Treating Diseases Associated with Metabolic Syndrome. J Med Food. 2017 Oct;20(10):933-943. doi: 10.1089/jmf.2016.0171. Epub 2017 Aug 9. PMID: 28792778; PMCID: PMC5651958.

[13] Ruiz-Ruiz JC, Moguel-Ordoñez YB, Segura-Campos MR. Biological activity of Stevia rebaudiana Bertoni and their relationship to health. Crit Rev Food Sci Nutr. 2017 Aug 13;57(12):2680-2690. doi: 10.1080/10408398.2015.1072083. PMID: 26479769.

[14] Lemus-Mondaca R, Vega-Gálvez A, Zura-Bravo L, Ah-Hen K. Stevia rebaudiana Bertoni, source of a high-potency natural sweetener: A comprehensive review on the biochemical, nutritional, and functional aspects. Food Chem. 2012 Jun 1;132(3):1121-1132. doi: 10.1016/j.foodchem.2011.11.140. Epub 2011 Dec 13. PMID: 29243591.

[15] Thana Lakshme, P.S., Gayathri, R., Vishnu Priya V. Preliminary Phytochemical Screening and Estimation of Total Phenolic Content of Aqueous Cladode Extract of Opuntia dilleniid. J. Res. Med. Dent. Sci. 2021 9(2): 254-257.

[16] Mithil Vora, Vishnu Priya V, Selvaraj J, Gayathri R, Kavitha S. Effect of Lupeol on proinflammatory Markers in Adipose Tissue of High-Fat Diet and Sucrose Induced Type-2 Diabetic Rats. J. Res. Med. Dent. Sci. 2021 9(10):116-121.

[17] Vishaka S, Sridevi G, Selvaraj J. An in vitro analysis on the antioxidant and anti-diabetic properties of Kaempferia galanga rhizome using different solvent systems. J Adv Pharm Technol Res. 2022 Dec;13(Suppl 2):S505-S509. doi: 10.4103/japtr.japtr_189_22. Epub 2022 Dec 30. PMID: 36798576; PMCID: PMC9926592.

[18] Skovsø S. Modeling type 2 diabetes in rats using high fat diet and streptozotocin. J Diabetes Investig. 2014 Jul;5(4):349-58. doi: 10.1111/jdi.12235. Epub 2014 May 19. PMID: 25411593; PMCID: PMC4210077.

[19] Holmes A, Coppey LJ, Davidson EP, Yorek MA. Rat Models of Diet-Induced Obesity and High Fat/Low Dose Streptozotocin Type 2 Diabetes: Effect of Reversal of High Fat Diet Compared to Treatment with Enalapril or Menhaden Oil on Glucose Utilization and Neuropathic Endpoints. J Diabetes Res. 2015;2015:307285. doi: 10.1155/2015/307285. Epub 2015 Jul 2. PMID: 26229968.

[20] Dev Arora, Gayathri R, Selvaraj J, Vishnu Priya V, Kavitha S. Vitamin C and E Down Regulates the Expression of C-JNK, IKKB, NF-kB in Adipose Tissue of PCB-Exposed Rats. J. Res. Med. Dent. Sci. 2021 9(11):39-44.

[21] Khan, HLA, Sridevi G, Selvaraj J, Preetha S. In vitro Anti-inflammatory Properties in Various Extracts (Ethanol, Chloroform and Aqueous) of Kaempferia galanga Linn Rhizome. J. Pharm. Res. Int. 2021 33 (47B): 476–481. DOI:https://doi.org/10.9734/jpri/2021/v33i47B33146.

[22] McGuinness OP, Ayala JE, Laughlin MR, Wasserman DH. NIH experiment in centralized mouse phenotyping: the Vanderbilt experience and recommendations for evaluating glucose homeostasis in the mouse. Am J Physiol Endocrinol Metab. 2009 Oct;297(4):E849-55. doi: 10.1152/ajpendo.90996.2008. Epub 2009 Jul 28. PMID: 19638507; PMCID: PMC2763792.

[23] Nagy C, Einwallner E. Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT). J Vis Exp. 2018 Jan 7;(131):56672. doi: 10.3791/56672. PMID: 29364280; PMCID: PMC5908452.

[24] Andrikopoulos S, Blair AR, Deluca N, Fam BC, Proietto J. Evaluating the glucose tolerance test in mice. Am J Physiol Endocrinol Metab. 2008 Dec;295(6):E1323-32. doi: 10.1152/ajpendo.90617.2008. Epub 2008 Sep 23. PMID: 18812462.

[25] Akifa Begum, Palati Sinduja, Priyadharshini R, Selvaraj Jayaraman. Estimation of Clinocopathological Correlation and Comparison of Salivary TNF-α among Normal and Post Radiotherapy Patients of Oral cancer-A Cross-Sectional Study. J. Res. Med. Dent. Sci. 2021 9(10): 92-97.

[26] Fathima Hinaz Z, Gayathri R, Selvaraj J, Vishnu Priya V, Kavitha, S, Gayathri R. Comparative Evaluation of Anti-Cholesterol Potential of Apple Cider Vinegar and Its Herbal Formulation with Allium Sativum and Honey-An In-Vitro Assay. J. Res. Med. Dent. Sci. 2021 9 (10),142-147.

[27] Logan IE, Bobe G, Miranda CL, Vasquez-Perez S, Choi J, Lowry MB, Sharpton TJ, Morgun A, Maier CS, Stevens JF, Shulzhenko N, Gombart AF. Germ-Free Swiss Webster Mice on a High-Fat Diet Develop Obesity, Hyperglycemia, and Dyslipidemia. Microorganisms. 2020 Apr 5;8(4):520. doi: 10.3390/microorganisms8040520. PMID: 32260528; PMCID: PMC7232377.

[28] Rotimi SO, Rotimi OA, Adelani IB, Onuzulu C, Obi P, Okungbaye R. Stevioside modulates oxidative damage in the liver and kidney of high fat/low streptozocin diabetic rats. Heliyon. 2018 May 31;4(5):e00640. doi: 10.1016/j.heliyon.2018.e00640. PMID: 29872771; PMCID: PMC5986550.

[29] Mounithaa N, Gayathri R, Selvaraj Jayaraman, Vishnu Priya V, Kavitha S. Effect of Piperine on an Nrf2/Keap 1 Signalling Mechanism in Adipose Tissue of High Fat Diet and Sucrose-Induced Experimental Diabetic Rats. J. Adv. Zool. 2023 44 (S5):232-39.

[30] Zhao RZ, Jiang S, Zhang L, Yu ZB. Mitochondrial electron transport chain, ROS generation and uncoupling (Review). Int J Mol Med. 2019 Jul;44(1):3-15. doi: 10.3892/ijmm.2019.4188. Epub 2019 May 8. PMID: 31115493; PMCID: PMC6559295.

[31] Padmapriya, A., Preetha, S., Selvaraj, J., Sridevi, G. (2022). Effect of Carica papaya seed extract on IL-6 and TNF-α in human lung cancer cell lines-an In vitro study. Res J Pharm Technol. 2022 15 (12): 5478-5482.

[32] Deng Y, Scherer PE. Adipokines as novel biomarkers and regulators of the metabolic syndrome. Ann N Y Acad Sci. 2010 Nov;1212:E1-E19. doi: 10.1111/j.1749-6632.2010.05875.x. Erratum in: Ann N Y Acad Sci. 2011 May;1226(1):50. PMID: 21276002; PMCID: PMC3075414.

[33] Kwon H, Pessin JE. Adipokines mediate inflammation and insulin resistance. Front Endocrinol (Lausanne). 2013 Jun 12;4:71. doi: 10.3389/fendo.2013.00071. PMID: 23781214; PMCID: PMC3679475.


[34] Jung UJ, Choi MS. Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci. 2014 Apr 11;15(4):6184-223. doi: 10.3390/ijms15046184. PMID: 24733068; PMCID: PMC4013623.

[35] Deenadayalan A, Subramanian V, Paramasivan V, Veeraraghavan VP, Rengasamy G, Coiambatore Sadagopan J, Rajagopal P, Jayaraman S. Stevioside Attenuates Insulin Resistance in Skeletal Muscle by Facilitating IR/IRS-1/Akt/GLUT 4 Signaling Pathways: An In Vivo and In Silico Approach. Molecules. 2021 Dec 20;26(24):7689. doi: 10.3390/molecules26247689. PMID: 34946771; PMCID: PMC8707280.

[36] Jayaraman S, Krishnamoorthy K, Prasad M, Veeraraghavan VP, Krishnamoorthy R, Alshuniaber MA, Gatasheh MK, Elrobh M, Gunassekaran. Glyphosate potentiates insulin resistance in skeletal muscle through the modulation of IRS-1/PI3K/Akt mediated mechanisms: An in vivo and in silico analysis. Int J Biol Macromol. 2023 Jul 1;242(Pt 2):124917. doi: 10.1016/j.ijbiomac.2023.124917. Epub 2023 May 18. PMID: 37207753.