Evaluation of the Effectiveness of Metformin and Black Rice Ethanol Extract Combination in Reducing Blood Glucose Levels and Protecting Kidney, Liver, and Pancreatic Cells
Main Article Content
Abstract
Metformin (MET), a first-line oral antidiabetic medicine, is known for its ability to increase insulin sensitivity. However, uncontrolled lactic acidosis, a potential side effect of MET, can cause organ injury. On the other hand, antioxidants like black rice bran (BRB), containing cyanidin-3-glucosidase (C3G), have demonstrated efficacy in preventing diabetic kidney injury and fibrosis due to oxidative stress. The objective of this study is to investigate the potential of combining the ethanol extract of black rice bran (EEBRB) with MET in the regulation of various parameters in hyperglycemic rats. In this study, 20 male rats were divided into different groups. They were treated for 21 days after being divided into the normal group, alloxan (ALX) group 150 mg/kg BW, MET 63 mg/kg BW, and a combination of MET 63 mg/kg BW and EEBRB 50 mg/kg BW. The results of the study indicate that both treatments properly controlled fasting blood glucose levels with no hypoglycemia over a duration of 21 days. Furthermore, histopathological examinations revealed significant protection against kidney, liver, and pancreatic injury in the group receiving the combination treatment. Although there was no statistically significant weight loss, the combination did not lead to excessive weight gain, a common concern with some antidiabetic medications. MET and EEBRB can regulate blood glucose levels and attenuate organ damage in animals with hyperglycemia. Further investigation is necessary to elucidate the processes underlying the safety and efficacy of the combination approach.
Downloads
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
How to Cite
References
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. Diabetes Res Clin Pract. 2019;157:107843.
Yerevanian A, Soukas AA. Metformin: Mechanisms in human obesity and weight loss. Curr Obes Rep. 2020;8(2):156–64.
Wu M, Xu H, Liu J, Tan X, Wan S, Guo M, Long Y, Xu Y. Metformin and fibrosis: A review of existing evidence and mechanisms. J Diabetes Res. 2021;2021:1–11.
Aggarwal N, Singla A, Mathieu C, Montanya E, Pfeiffer AFH, Johnsson E, Zhao J, Iqbal N, Bailey C. Metformin extended-release versus immediate-release: An international, randomized, double-blind, head-to-head trial in pharmacotherapy-naïve patients with type 2 diabetes. Diabetes, Obes Metab. 2018;20(2):463–7.
Peng Z, Zheng Y. Ganjiang Huangqin Huanglian Renshen Decoction improves insulin sensitivity by regulating intestinal flora in rats with type 2 diabetes mellitus. Trop J Pharm Res. 2023;22(April):833–9.
Yerevanian A, Soukas AA. Metformin: Mechanisms in human obesity and weight loss. Curr Obes Rep. 2019;8(2):156–64.
Sepahi MA, Mehrabi S, Valizadeh R, Kellner SJ, Mirzazadeh A, Ebrahimi S. Nephroprotection and chemotherapy sensitivity impact of metformin during cisplatin therapy; an updated review. J Nephropathol. 2019;8(4).
Zhang H, Liu F, Huang Y, Liu W. The role of metformin in the management of endometriosis: A systematic review and meta-analysis. Trop J Pharm Res. 2023;22(5):1115–20.
Reeker W, Schneider G, Felgenhauer N, Tempel G, Kochs E. Metformin-induced lactacidosis. Dtsch Medizinische Wochenschrift. 2000;125(9):249–51.
Lee HW, Lee JS, Kim BK, Park JY, Kim DY, Ahn SH, Kim SU. Evolution of liver fibrosis and steatosis markers in patients with type 2 diabetes after metformin treatment for 2 years. J Diabetes Complications [Internet]. 2021;35(1):107747. Available from: https://doi.org/10.1016/j.jdiacomp.2020.107747
Agustini R, Sanjaya GM, Herdyastuti N. In vivo assessment of nanocapsules of black rice (Zizania aquatica) yeast extract in diabetes mellitus type 2-induced mice (Mus musculus). Trop J Nat Prod Res. 2023;7(1):2237–43.
Les F, Cásedas G, Gómez C, Moliner C, Valero MS, López V. The role of anthocyanins as antidiabetic agents: From molecular mechanisms to in vivo and human studies. J Physiol Biochem. 2020;77(1):109–31.
Alnamshan MM. Antioxidant extract of black rice prevents renal dysfunction and renal fibrosis caused by ethanol-induced toxicity. Brazilian J Biol. 2022;82:1–10.
Wahyuni AS, Hakim L, Nurrochmad A, Astuti P. The sinergistic effect of black rice bran extract and glibenclamide on protecting renal, hepatic, and pancreatic cells in alloxan induced rats. Int J Pharm Res. 2020;12(1):509–17.
Watanabe M. Effects of black rice containing anthocyanins on plasma and hepatic parameters in type 2 diabetic db/db mice. Food Sci Technol Res. 2016;22(5):719–25.
Ailanen L, Bezborodkina NN, Virtanen L, Ruohonen ST, Malova AV, Okovityi SV, Chistyakova EY, Savontaus E. Metformin normalizes the structural changes in glycogen preceding prediabetes in mice overexpressing neuropeptide Y in noradrenergic neurons. Pharmacol Res Perspect. 2018;6(2).
Wahyuni AS, Munawaroh R, Da’i M. Antidiabetic mechanism of ethanol extract of black rice bran on diabetic rats. Natl J Physiol Pharm Pharmacol. 2016;6(2):106–10.
Hou Z, Qin P, Zhang Y, Cui S, Ren G. Identification of anthocyanins isolated from black rice (Oryza sativa L.) and their degradation kinetics. Food Res Int. 2013;50(2):691–7.
Sutrisna E, Hervian L, Sahadewa FA. Hypoglicemic effect of 70% ethanolic extract of Tinosporacrispa L. (Bratawali) stem from Indonesia in Wistar rat induced by alloxan. J Clin Diag Res. 2018;12(9):FF01–3.
Muhtadi M, Haryoto H, Sujono TA, Suhendi A. Antidiabetic and antihypercholesterolemia activities of rambutan (Nephelium lappaceum L.) and durian (Durio zibethinus Murr.) fruit peel extracts. J Appl Pharm Sci. 2016;6(4):2231–3354.
Mojibi N, Rasouli M. Comparison of methods to assay liver glycogen fractions: The effects of starvation. J Clin Diagnostic Res. 2017;11(3):BC17–20.
Suarsana IN, Priosoeryanto BP, Wresdiyati T, Bintang M. Synthesis of liver and muscle glycogen on diabetic rats by administrated of extract tempe. J Vet. 2010;11(3):190–5.
Carvalho CDDE, Augusto C, Filho K, Luiz A, Rocha DA, Sanchez A, Silva R. Glycogen kinetics of Wistar rats: Different exercise intensities and tissue analyzed influence. Int J Exerc Sci. 2022;15(2):289–99.
Elkotby D, Hassan AK, Emad R, Bahgat I. Histological changes in islets of Langerhans of pancreas in alloxan-induced diabetic rats following Egyptian honey bee venom treatments. Int J Pure Appl Zool. 2018;6(1):1–6.
Gong L, Goswami S, Giacomini KM, Altman RB, Klein TE. Metformin pathways. Pharmacogenet Genomics. 2012;22(11):820–7.
Liu X, Wang K, Zhou J, Sullivan MA, Liu Y, Gilbert RG, Deng B. Metformin and Berberine suppress glycogenolysis by inhibiting glycogen phosphorylase and stabilizing the molecular structure of glycogen in db/db mice. Carbohydr Polym. 2020;243.
Olamoyegun MA, Omisore NO, Yusuf AO, Odewale TE. Assessment of pharmacodynamic interactions and toxicological effects of Vernonia amygydalina –Metformin co-administration on streptozotocin-induced diabetic Wistar rats. Trop J Nat Prod Res. 2022;6(12):2073–80.
Baker C, Retzik-Stahr C, Singh V, Plomondon R, Anderson V, Rasouli N. Should metformin remain the first-line therapy for treatment of type 2 diabetes? Therapeutic Adv Endocrinol Metab. 2020;12:1–13.
Tantipaiboonwong P, Pintha K, Chaiwangyen W, Chewonarin T, Pangjit K, Chumphukam O, Kangwan N, Suttajit M. Anti-hyperglycaemic and anti-hyperlipidaemic effects of black and red rice in streptozotocin-induced diabetic rats. SciAsia. 2017;43(5):281–8.
Bae IY, An JS, Oh IK, Lee HG. Optimized preparation of anthocyanin-rich extract from black rice and its effects on in vitro digestibility. Food Sci Biotechnol. 2017;26(5):1415–22.
Jia Y, Wu C, Kim YS, Yang SO, Kim Y, Kim JS, Jeong MY, Lee JH, Kim B, Lee S, Oh HS, Kim J, So MY, Yoon YE, Thach TT, Park TH, Lee SJ. A dietary anthocyanin cyanidin-3-O-glucoside binds to PPARs to regulate glucose metabolism and insulin sensitivity in mice. Commun Biol. 2020;3(1):2–11.
Vaidyanathan K. Textbook of biochemistry for medical students. 9th ed. Vasudevan DM, editor. Textbook of Biochemistry for Medical Students. New Delhi: Jaypee Brothers Medical Publishers; 2016.
Forbes JM, Cooper ME. Mechanisms of diabetic complications. Physiol Rev. 2013;93(1):137–88.
Fornasaro S, Ziberna L, Gasperotti M, Tramer F, Vrhovšek U, Mattivi F, Passamonti S. Determination of cyanidin 3-glucoside in rat brain, liver and kidneys by UPLC/MS-MS and its application to a short-term pharmacokinetic study. Sci Rep. 2016;6(22815):1–11.
Lucchesi AN, Cassettari LL, Spadella CT. Alloxan-induced diabetes causes morphological and ultrastructural changes in rat liver that resemble the natural history of chronic fatty liver disease in humans. J Diabetes Res. 2015;2015(5):1–11.
Patley C, Srivastava DN, Patley R, Kohli S. Alloxan induced oxidative stress and impairment of oxidative defense system in rats. Asian J Biomed Pharm Sci. 2012;2(15):58–61.
Marin DP, Bolin AP, MacEdo RDCS, Sampaio SC, Otton R. ROS production in neutrophils from alloxan-induced diabetic rats treated in vivo with astaxanthin. Int Immunopharmacol. 2011;11(1):103–9.