ANTIOXIDANT AND ANTI-INFLAMMATORY ACTIVITIES OF STEVIA REBAUDIANA LEAF EXTRACT IN DIABETIC RATS

  • George O. Eidangbe Ambrose Alli University
Keywords: Diabetes, Stevia rebaudiana, Oxidative stress, Antioxidant, Inflammation

Abstract

This study explores the antioxidant and anti-inflammatory effects of Stevia rebaudiana aqueous leaf extract in alloxan-induced diabetic male Wistar rats. Thirty rats, comprising six normoglycemic controls (NC) and twenty-four diabetic rats were used. The diabetic rats were divided into four groups (n = 6 each): DC, diabetic rats administered distilled water; DGL, diabetic rats treated with glibenclamide; DSR100 and DSR200, diabetic rats treated with 100 and 200 mg/kg S. rebaudiana extract, respectively. Treatments were administered daily via gavage for 15 days. After 15 days, animals were fasted overnight, euthanized by cervical dislocation, and blood samples collected for serum analyses. Body weight, liver weight, fasting blood glucose (FBG), and serum malondialdehyde (MDA) level were monitored. Antioxidant enzyme activitiessuperoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)were also measured, alongside serum levels of pro-inflammatory cytokines interleukin-1 (IL-1), tumor necrosis factor- (TNF-), and the anti-inflammatory cytokine interleukin-10 (IL-10). The findings revealed that S. rebaudiana extract significantly reduced serum MDA levels and enhanced the activities of antioxidant enzymes (SOD, CAT, and GPx) in diabetic rats. Significant (p<0.05) improvements in FBG, liver-to-body weight ratio, and cytokine profiles were observed in the DSR100 and DSR200 groups compared with the DC. Specifically, the extract significantly decreased IL-1 and TNF- while elevating IL-10 level. These effects were dose-dependent, with 200 mg/kg dose showing the most pronounced benefits. In conclusion, aqueous leaf extract of S. rebaudiana demonstrates robust antioxidant and anti-inflammatory activities, effectively attenuating oxidative stress-induced inflammatory responses in alloxan-induced diabetic rats.

References

Abdi, M., Alizadeh, F., Daneshi, E., Abouzaripour, M., Fathi, F., & Rahimi, K. (2023). Ameliorative effect of Stevia rebaudiana Bertoni on sperm parameters, in vitro fertilization, and early embryo development in a streptozotocin-induced mouse model of diabetes. Zygote, 31(5), 475-482. https://doi.org/10.1017/s0967199423000266 DOI: https://doi.org/10.1017/S0967199423000266

Adebayo, K. O., Owolabi, M. A., & Khan, M. E. (2024). Comparative anti-diabetic effects of ethanol extracts from leaves, seeds and pods of Moringa oleifera on alloxan induced diabetic rats. FUDMA Journal of Sciences, 8(6), 128 - 136. https://doi.org/10.33003/fjs-2024-0806-2771 DOI: https://doi.org/10.33003/fjs-2024-0806-2771

Al-Khayri, J. M., Rashmi, R., Toppo, V., Chole, P. B., Banadka, A., Sudheer, W. N., ... & Rezk, A. A. S. (2023). Plant secondary metabolites: The weapons for biotic stress management. Metabolites, 13(6), 716. https://doi.org/10.3390/metabo13060716 DOI: https://doi.org/10.3390/metabo13060716

Ashraf, M. V., Khan, S., Misri, S., Gaira, K. S., Rawat, S., Rawat, B., ... & Ahmad, S. (2024). High-Altitude Medicinal Plants as Promising Source of Phytochemical Antioxidants to Combat Lifestyle-Associated Oxidative Stress-Induced Disorders. Pharmaceuticals, 17(8). https://doi.org/10.3390/ph17080975 DOI: https://doi.org/10.3390/ph17080975

Bagheri, H., Ghasemi, F., Barreto, G. E., Rafiee, R., Sathyapalan, T., & Sahebkar, A. (2020). Effects of curcumin on mitochondria in neurodegenerative diseases. Biofactors, 46(1), 5-20. https://doi.org/10.1002/biof.1566 DOI: https://doi.org/10.1002/biof.1566

Bangar, N. S., Gvalani, A., Ahmad, S., Khan, M. S., & Tupe, R. S. (2022). Understanding the role of glycation in the pathology of various non-communicable diseases along with novel therapeutic strategies. Glycobiology, 32(12), 1068-1088. https://doi.org/10.1093/glycob/cwac060 DOI: https://doi.org/10.1093/glycob/cwac060

Boye, K. S., Ford, J. H., Thieu, V. T., Lage, M. J., & Terrell, K. A. (2023). The association between obesity and the 5-year prevalence of morbidity and mortality among adults with type 2 diabetes. Diabetes Therapy, 14(4), 709-721. https://doi.org/10.1007/s13300-023-01384-7 DOI: https://doi.org/10.1007/s13300-023-01384-7

Caturano, A., DAngelo, M., Mormone, A., Russo, V., Mollica, M. P., Salvatore, T., ... & Sasso, F. C. (2023). Oxidative stress in type 2 diabetes: impacts from pathogenesis to lifestyle modifications. Current Issues in Molecular Biology, 45(8), 6651-6666. doi: 10.3390/cimb45080420 DOI: https://doi.org/10.3390/cimb45080420

Chen, X., Xie, N., Feng, L., Huang, Y., Wu, Y., Zhu, H., ... & Zhang, Y. (2024). Oxidative stress in diabetes mellitus and its complications: From pathophysiology to therapeutic strategies. Chinese Medical Journal, 10-1097. https://doi.org/10.1097/CM9.0000000000003230 DOI: https://doi.org/10.1097/CM9.0000000000003230

Elshafey, M., Erfan, O. S., Risha, E., Badawy, A. M., Ebrahim, H. A., El-Sherbiny, M., El-Shenbaby, I., Enan, E. T., Almadani, M. E., & Eldesoqui, M. (2023). Protective effect of Stevia on diabetic induced testicular damage: An immunohistochemical and ultrastructural study. European Review for Medical & Pharmacological Sciences, 27(22). https://doi.org/10.26355/eurrev_202311_34473 .

Forman H.J., Zhang H. Targeting oxidative stress in disease: Promise and limitations of antioxidant therapy. Nat. Rev. Drug Discov. 2021;20:689. https://doi.org/10.1038/s41573-021-00233-1 . DOI: https://doi.org/10.1038/s41573-021-00233-1

Geng, Y., Faber, K. N., de Meijer, V. E., Blokzijl, H., & Moshage, H. (2021). How does hepatic lipid accumulation lead to lipotoxicity in non-alcoholic fatty liver disease?. Hepatology international, 15, 21-35. https://doi.org/10.1007/s12072-020-10121-2 DOI: https://doi.org/10.1007/s12072-020-10121-2

Hong, J., Chen, L., Jeppesen, P. B., Nordentoft, I., & Hermansen, K. (2006). Stevioside counteracts the -cell hypersecretion caused by long-term palmitate exposure. American Journal of Physiology-Endocrinology and Metabolism, 290(3), E416-E422. https://doi.org/10.1152/ajpendo.00331.2005 DOI: https://doi.org/10.1152/ajpendo.00331.2005

Kabir, M. T., Tabassum, N., Uddin, M. S., Aziz, F., Behl, T., Mathew, B., ... & Aleya, L. (2021). Therapeutic potential of polyphenols in the management of diabetic neuropathy. EvidenceBased Complementary and Alternative Medicine, 2021(1), 9940169. https://doi.org/10.1155/2021/9940169 DOI: https://doi.org/10.1155/2021/9940169

Karganov, M. Y., Alchinova, I. B., Tinkov, A. A., Medvedeva, Y. S., Lebedeva, M. A., Ajsuvakova, O. P., Polyakova, M. V., Skalnaya, M. G., Burtseva, T. I., Notova, S. V., & Khlebnikova, N. N. (2020). Streptozotocin (STZ)-induced diabetes affects tissue trace element content in rats in a dose-dependent manner. Biological Trace Element Research, 198, 567-574. https://doi.org/10.1007/s12011-020-02090-2 DOI: https://doi.org/10.1007/s12011-020-02090-2

Kurek, J. M., & Krejpcio, Z. (2019). The functional and health-promoting properties of Stevia rebaudiana Bertoni and its glycosides with special focus on the antidiabetic potentialA review. Journal of Functional Foods, 61, 103465. https://doi.org/10.1016/j.jff.2019.103465 DOI: https://doi.org/10.1016/j.jff.2019.103465

Latha, S., Chaudhary, S., & Ray, R. S. (2017). Hydroalcoholic extract of Stevia rebaudiana bert. leaves and stevioside ameliorates lipopolysaccharide induced acute liver injury in rats. Biomedicine & Pharmacotherapy, 95, 1040-1050. https://doi.org/10.1016/j.biopha.2017.08.082 . DOI: https://doi.org/10.1016/j.biopha.2017.08.082

Li, H., Xu, Q., Xu, C., Hu, Y., Yu, X., Zhao, K., ... & Kuang, H. (2021). Bicyclol regulates hepatic gluconeogenesis in rats with type 2 diabetes and non-alcoholic fatty liver disease by inhibiting inflammation. Frontiers in Pharmacology, 12, 644129. https://doi.org/10.3389/fphar.2021.644129 DOI: https://doi.org/10.3389/fphar.2021.644129

Lian, C. Y., Zhai, Z. Z., Li, Z. F., & Wang, L. (2020). High fat diet-triggered non-alcoholic fatty liver disease: A review of proposed mechanisms. Chemico-biological interactions, 330, 109199. https://doi.org/10.1016/j.cbi.2020.109199 DOI: https://doi.org/10.1016/j.cbi.2020.109199

Loureno S.C., Moldo-Martins M., Alves V.D. Antioxidants of natural plant origins: From sources to food industry applications. Molecules. 2019;24:4132. https://doi.org/10.3390/molecules24224132 DOI: https://doi.org/10.3390/molecules24224132

Masenga, S. K., Kabwe, L. S., Chakulya, M., & Kirabo, A. (2023). Mechanisms of oxidative stress in metabolic syndrome. International journal of molecular sciences, 24(9), 7898. https://doi.org/10.3390/ijms24097898 DOI: https://doi.org/10.3390/ijms24097898

Oluba, O. M., Adebiyi, F. D., Dada, A. A., Ajayi, A. A., Adebisi, K. E., Josiah, S. J., & Odutuga, A. A. (2019). Effects of Talinum triangulare leaf flavonoid extract on streptozotocin-induced hyperglycemia and associated complications in rats. Food Science & Nutrition, 7(2), 385-394. https://doi.org/10.1002/fsn3.765 DOI: https://doi.org/10.1002/fsn3.765

Ong, K. L., Stafford, L. K., McLaughlin, S. A., Boyko, E. J., Vollset, S. E., Smith, A. E., ... & Brauer, M. (2023). Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet, 402(10397), 203-234. https://doi.org/10.1016/S0140-6736(23)01301-6 DOI: https://doi.org/10.1016/S0140-6736(23)01301-6

Poprac P., Jomova K., Simunkova M., Kollar V., Rhodes C.J., Valko M. Targeting Free Radicals in Oxidative Stress-Related Human Diseases. Trends Pharmacol. Sci. 2017;38:592607. https://doi.org/10.1016/j.tips.2017.04.005 DOI: https://doi.org/10.1016/j.tips.2017.04.005

Prabhakar, P. K. (2024). Glucose to Complications: Understanding Secondary Effects in Diabetes Mellitus. Sumatera Medical Journal, 7(2), 87-95. https://doi.org/10.32734/sumej.v7i2.15998 DOI: https://doi.org/10.32734/sumej.v7i2.15998

Raina, J., Firdous, A., Singh, G., Kumar, R., & Kaur, C. (2024). Role of polyphenols in the management of diabetic complications. Phytomedicine, 122, 155155. https://doi.org/10.1016/j.phymed.2023.155155 DOI: https://doi.org/10.1016/j.phymed.2023.155155

Schmedes, A., & Hlmer, G. (1989). A new thiobarbituric acid (TBA) method for determining free malondialdehyde (MDA) and hydroperoxides selectively as a measure of lipid peroxidation. Journal of the American Oil Chemists' Society, 66(6), 813-817. DOI: https://doi.org/10.1007/BF02653674

Sharifi-Rad, M., Anil Kumar, N. V., Zucca, P., Varoni, E. M., Dini, L., Panzarini, E., ... & Sharifi-Rad, J. (2020). Lifestyle, oxidative stress, and antioxidants: back and forth in the pathophysiology of chronic diseases. Frontiers in physiology, 11, 694. https://doi.org/10.3389/fphys.2020.00694 DOI: https://doi.org/10.3389/fphys.2020.00694

Shibib, L., Al-Qaisi, M., Guess, N., Miras, A. D., Greenwald, S. E., Pelling, M., & Ahmed, A. (2024). Manipulation of Post-Prandial Hyperglycaemia in Type 2 Diabetes: An Update for Practitioners. Diabetes, Metabolic Syndrome and Obesity, 3111-3130. https://doi.org/10.2147/DMSO.S458894 DOI: https://doi.org/10.2147/DMSO.S458894

Singh, V., Akansha, Islam, Z., & Shaida, B. (2023). Medicinal Plants: Sustainable Scope to Nutraceuticals. In Sustainable Food Systems (Volume II) SFS: Novel Sustainable Green Technologies, Circular Strategies, Food Safety & Diversity (pp. 205-236). Cham: Springer Nature Switzerland. DOI: https://doi.org/10.1007/978-3-031-46046-3_11

Sultana, N., Saini, P. K., Kiran, S. R., & Kanaka, S. (2023). Exploring the antioxidant potential of medicinal plant species: A comprehensive review. Journal of Plant Biota. http://dx.doi.org/10.51470/JPB.2023.02.02.09 DOI: https://doi.org/10.51470/JPB.2023.02.02.09

Wei, F., Zhu, H., Li, N., Yu, C., Song, Z., Wang, S., ... & Sun, L. (2021). Stevioside activates AMPK to suppress inflammation in macrophages and protects mice from LPS-induced lethal shock. Molecules, 26(4), 858. https://doi.org/10.3390/molecules26040858 DOI: https://doi.org/10.3390/molecules26040858

Zhao, C., Yang, C., Wai, S. T. C., Zhang, Y., P. Portillo, M., Paoli, P., ... & Cao, H. (2019). Regulation of glucose metabolism by bioactive phytochemicals for the management of type 2 diabetes mellitus. Critical Reviews in Food Science and Nutrition, 59(6), 830-847. https://doi.org/10.1080/10408398.2018.1501658 DOI: https://doi.org/10.1080/10408398.2018.1501658

Zhao, X., An, X., Yang, C., Sun, W., Ji, H., & Lian, F. (2023). The crucial role and mechanism of insulin resistance in metabolic disease. Frontiers in endocrinology, 14, 1149239. https://doi.org/10.3389/fendo.2023.1149239 DOI: https://doi.org/10.3389/fendo.2023.1149239

Zou, X., Tan, Q., Goh, B. H., Lee, L. H., Tan, K. L., & Ser, H. L. (2020). Sweeterthan its name: anti-inflammatory activities of Stevia rebaudiana. All Life, 13(1), 286-309. https://doi.org/10.1080/26895293.2020.1771434 DOI: https://doi.org/10.1080/26895293.2020.1771434

Published
2025-01-31
How to Cite
EidangbeG. O. (2025). ANTIOXIDANT AND ANTI-INFLAMMATORY ACTIVITIES OF STEVIA REBAUDIANA LEAF EXTRACT IN DIABETIC RATS. FUDMA JOURNAL OF SCIENCES, 9(1), 301 - 306. https://doi.org/10.33003/fjs-2025-0901-2944