Gamma-oryzanol: a novel promising supplement for diabetes mellitus
Main Article Content
Abstract
The global prevalence of diabetes is rising at an alarming rate, with nearly 11% of adults currently affected. Projections estimate that by 2045, approximately 800 million individuals—1 in every 8 people—will have diabetes, representing a 46% increase in cases. Effective dietary management, however, offers the potential to delay or reduce diabetes-related complications. Gamma-oryzanol (γ-ORZ), a bioactive compound in brown rice (BR), has shown promising effects on type 2 diabetes mellitus (T2DM) and its complications, as evidenced by various scientific studies. Despite its potential, γ-ORZ's mechanisms of action remain underexplored, and BR consumption is less prevalent compared to white rice (WR). This review aimed to examine the effects of γ-ORZ on diabetes, promoting further research and encouraging the adoption of BR in dietary practices. Relevant studies were identified through a systematic search of PubMed, ScienceDirect, and Google Scholar for articles published between January 2013 and December 2023 using the keywords “(Gamma-oryzanol OR γ-oryzanol OR γ-ORZ) AND (Diabetes Mellitus OR Type-2 diabetes mellitus OR T2DM OR Hyperglycemia OR Insulin Resistance).” From an initial pool of 1,912 articles, 15 studies meeting the inclusion criteria were reviewed. Findings revealed that γ-ORZ exhibits antihyperglycemic, antidyslipidemic, anti-inflammatory, and antioxidant properties. It mitigates β-cell dysfunction, improves adipocyte function, enhances insulin secretion and sensitivity, and alleviates diabetic cardiomyopathy. This review underscores γ-ORZ's therapeutic potential in managing diabetes and its complications, while highlighting the need for more robust studies to validate its efficacy and compare it with standard treatments.
Article Details
Section
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The journal allows the authors to hold the copyright without restrictions and allow the authors to retain publishing rights without restrictions.
How to Cite
References
IDF Diabetes Atlas 2021. 10th ed. Brussels, Belgium: International Diabetes Federation; 2021.
World Health Organization. Global report on diabetes. Geneva: World Health Organization; 2016.
Varshney A, Rawat R, editors. A concise textbook of diabetes. 1st ed. Amritsar (India): Dentomed Publishing House; 2021.
Rezaeiamiri ER, Bahramsoltani R, Rahimi BR. Plant-derived natural agents as dietary supplements for the regulation of glycosylated hemoglobin: a review of clinical trials, Clin Nutr 2020;39:331–42. https://doi.org/10.1016/j. clnu.2019.02.006.
Kahaly GJ Hansen MP. Type 1 diabetes-associated autoimmunity. Autoimmun Rev 2016;15:644-8. doi: 10.1016/j.autrev.2016.02.017.
Burrack AL, Martinov T, Fife BT. T cell-mediated beta cell destruction: autoimmunity and alloimmunity in the context of type 1 diabetes. Front Endocrinol (Lausanne) 2017;8:343. doi: 10.3389/fendo.2017.00343.
Banday MZ, Sameer A. S., Nissar S. Pathophysiology of diabetes: an overview. Avicenna J Med 2020;10:174-88. doi: 10.4103/ajm.ajm_53_20.
Khin PP, Lee JH, Jun HS. Pancreatic beta-cell dysfunction in type 2 diabetes. Eur J Inflamm 2023;21:1-13. doi: 10.1177/1721727X231154152.
Galicia-Garcia U, Benito-Vicente A, Jebari S, et al. Pathophysiology of type 2 diabetes mellitus. Int J Mol Sci 2020;21:6275. doi: 10.3390/ijms21176275.
García-Aguilar A, Guillén C. Targeting pancreatic beta cell death in type 2 diabetes by polyphenols. Front Endocrinol 2022;13:1052317. doi: 10.3389/fendo.2022.1052317.
Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol 2018; 14:88–98. doi: 10.1038/nrendo.2017.151.
Yamamoto WR, Bone RN, Sohn P, et. al. Endoplasmic reticulum stress alters ryanodine receptor function in the murine pancreatic beta cell. J Biol Chem 2019;294:168–81. doi: 10.1074/jbc.RA118.005683.
Halban PA, Polonsky KS, Bowden DW, et. al. Beta-cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment. J Clin Endocrinol Metab 2014;99: 1983-92. doi: 10.1210/jc.2014-1425.
Czech MP. Insulin action and resistance in obesity and type 2 diabetes. Nat Med 2017; 23:804–14. doi: 10.1038/nm.4350.
Pearson T, Wattis JA, King JR, MacDonald IA, Mazzatti DJ. The effects of insulin resistance on individual tissues: an application of a mathematical model of metabolism in humans. Bull Math Biol 2016; 78:1189–217. doi: 10.1007/s11538-016-0181-1.
Borén, J. Öörni K, Catapano AL. The link between diabetes and cardiovascular disease. Atherosclerosis 2024;394:117607. doi: 10.1016/j.atherosclerosis.2024.117607.
Laakso M, Kuusisto J. Insulin resistance and hyperglycaemia in cardiovascular disease development. Nat Rev Endocrinol 2014;10:293–302. doi: 10.1038/nrendo.2014.29.
Pansuria M, Xi H, Li L, Yang XF, Wang H. Insulin resistance, metabolic stress, and atherosclerosis. Front Biosci (Schol Ed) 2012;4: 916-31. doi: 10.2741/s308.
Ormazabal V, Nair S, Elfeky O, Aguayo C, Salomon C, Zuñiga FA.. Association between insulin resistance and the development of cardiovascular disease. Cardiovasc Diabetol 2018;17:122. https://doi.org/10.1186/s12933-018-0762-4.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2014;37:S81-90. doi: 10.2337/dc14-S081.
Govindarajan Venguidesvarane A, Jasmine A, Varadarajan S, et al. Prevalence of vascular complications among type 2 diabetic patients in a rural health center in South India. J Prim Care Community Health 2020;11:1-11. doi: 10.1177/2150132720959962.
Liu Z, Liu X, Ma Z, Guan T. Phytosterols in rice bran and their health benefits. Front Nutr 2023;10:1287405. https://doi.org/10.3389/fnut.2023.1287405.
Nikooyeh B, Zargaraan A, Ebrahimof S, et. al. Daily consumption of γ-oryzanol-fortified canola oil, compared with unfortified canola and sunflower oils, resulted in a better improvement of certain cardiometabolic biomarkers of adult subjects with type 2 diabetes: a randomized controlled clinical trial. Eur J Med Res 2023;28: 416. doi: 10.1186/s40001-023-01409-8.
Mattei L, Francisqueti-Ferron FV, Garcia JL, et. al. Antioxidant and anti-inflammatory properties of gamma- oryzanol attenuates insulin resistance by increasing GLUT- 4 expression in skeletal muscle of obese animals, Mol Cell Endocrinol 2021;537:111423. https://doi.org/10.1016/j.mce.2021.111423.
Pereira C, Lourenço VM, Menezes R, Brites C. Rice compounds with impact on diabetes control. Foods 2021;10:1992. doi: 10.3390/foods10091992.
Malik VS, Sudha V, Wedick NM, et al. Substituting brown rice for white rice on diabetes risk factors in India: a randomised controlled trial. Br J Nutr 2019;121:1389-97. doi: 10.1017/S000711451900076X.
Wang O, Liu J, Cheng Q, et al. Effects of ferulic acid and γ-oryzanol on high-fat and high-fructose diet-induced metabolic syndrome in rats. PLoS ONE 2015;10:e0118135. https://doi.org/10.1371/journal.pone.0118135.
Kozuka C, Sunagawa C, Ueda R, et. al. γ-oryzanol protects pancreatic β-cells against endoplasmic reticulum stress in male mice. Endocrinology 2015;156:1242–50. doi: 10.1210/en.2014-1748.
Müller TD, Finan B, Bloom SR, et al. Glucagon-like peptide 1 (GLP-1). Mol Metab 2019;30:72-130. doi: 10.1016/j.molmet.2019.09.010.
Kozuka C, Sunagawa C, Ueda R, et. al. A novel insulinotropic mechanism of whole grain-derived γ-oryzanol via the suppression of local dopamine D2 receptor signalling in mouse islet. Br J Pharmacol 2015;172:4519–34. doi: 10.1111/bph.13236.
Caturano A, D'Angelo M, Mormone A, et al. Oxidative stress in type 2 diabetes: impacts from pathogenesis to lifestyle modifications. Curr Issues Mol Biol 2023;45:6651-66. doi: 10.3390/cimb45080420.
González P, Lozano P, Ros G, Solano F. Hyperglycemia and oxidative stress: an integral, updated and critical overview of their metabolic interconnections. Int J Mol Sci 2023;24:9352. doi: 10.3390/ijms24119352.
Sansenya S, Payaka A, Mansalai P. Inhibitory efficacy of cycloartenyl ferulate against -glucosidase and -amylase and its increased concentration in gamma-irradiated rice (germinated rice). Prev Nutr Food Sci 2023;28: 170-7. doi: 10.3746/pnf.2023.28.2.170.
Chauhan K, Chauhan B. Rice bran oil and oryzanol attenuates dyslipidemia and oxidative stress in atherogenic diet fed rats. Int J Med Pharmaceut Sci 2015;5:53-68.
Kozuka C, Shimizu-Okabe C, Takayama C, et. al. Marked augmentation of PLGA nanoparticle-induced metabolically beneficial impact of γ-oryzanol on fuel dyshomeostasis in genetically obese-diabetic ob/ob mice. Drug Deliv 2017;24: 558–68. doi: 10.1080/10717544.2017.1279237.
Guo XX, Zeng Z, Qian YZ, et. al. Wheat flour, enriched with γ-oryzanol, phytosterol, and ferulic acid, alleviates lipid and glucose metabolism in high-fat-fructose-fed rats. Nutrients 2019;11: 1697. doi:10.3390/nu11071697.
Bhaskaragoud, G, Chatterjee, P, Kumar, GS. Effect of oryzanol concentrate on hypolipidemic properties and antioxidant enzymes of liver in high fat fed and low STZ induced-male Wistar rats. Biomedicine 2020; 40:25-31.
Lin HL, Lin SH, Shen KP, et al. Efficiency comparison of PGBR extract and γ-oryzanol in antioxidative stress and anti-inflammatory properties against metabolic syndrome. J Food Biochem 2020;44:e13129. doi: 10.1111/jfbc.13129.
Nakayama T, Nagai Y, Uehara Y, et. al. Eating glutinous brown rice twice a day for 8 weeks improves glycemic control in Japanese patients with diabetes mellitus. Nutr Diabetes 2017;7: e273. doi:10.1038/nutd.2017.26.
Masuzaki H, Kozuka C, Okamoto S, Yonamine M, Tanaka H, Shimabukuro M. Brown rice-specific γ-oryzanol as a promising prophylactic avenue to protect against diabetes mellitus and obesity in humans. J Diabetes Investig 2019;10: 18-25. doi: 10.1111/jdi.12892.
Bumrungpert A, Lilitchan S, Tuntipopipat S, Tirawanchai N, Komindr S. Ferulic acid supplementation improves lipid profiles, oxidative stress, and inflammatory status in hyperlipidemic subjects: a randomized, double-blind, placebo-controlled clinical trial. Nutrients 2018;10:713. doi: 10.3390/nu10060713.
Luo L, Liu M. Adipose tissue in control of metabolism. J Endocrinol 2016;231:R77–R99. doi: 10.1530/JOE-16-0211.
Parimisetty A, Dorsemans AC, Awada R, Ravanan P, Diotel N, Lefebvre d’Hellencourt, C. Secret talk between adipose tissue and central nervous system via secreted factors-an emerging frontier in the neurodegenerative research. J Neuroinflammation 2016;13:67. doi: 10.1186/s12974-016-0530-x.
Clemente-Suárez VJ, Redondo-Flórez L, Beltrán-Velasco AI, et al. The role of adipokines in health and disease. Biomedicines 2023;11:1290. doi: 10.3390/biomedicines11051290.
Kirichenko TV, Markina YV, Bogatyreva AI, Tolstik TV, Varaeva YR, Starodubova AV. The role of adipokines in inflammatory mechanisms of obesity. Int J Mol Sci 2022;23:14982. doi: 10.3390/ijms232314982.
Peng J, Chen Q, Wu C. The role of adiponectin in cardiovascular disease. Cardiovasc Pathol 2023; 64:107514. https://doi.org/10.1016/j.carpath.2022.107514.
Francisqueti FV, Minatel IO, Ferron AJT, et. al. Effect of gamma-oryzanol as therapeutic agent to prevent cardiorenal metabolic syndrome in animals submitted to high sugar-fat diet. Nutrients 2017;9:1299. doi: 10.3390/nu9121299.
Hirano T. Pathophysiology of diabetic dyslipidemia. J Atheroscler Thromb 2018;25:771–82. doi: 10.5551/jat.RV17023.
Daya R, Bayat Z, Raal FJ. Prevalence and pattern of dyslipidemia in type 2 diabetes mellitus patients at a tertiary care hospital. J Endocrinol Metabol Diabetes South Africa 2017;22:31–5. doi: 10.1080/16089677.2017.1360064.
Ambachew H, Shimelis T, Lemma K. Dyslipidemia among diabetic patients in Southern Ethiopia. J Diabetes Endocrinol 2015;6:19–24. doi:10.5897/JDE2015.0086.
Pappan N, Awosika AO, Rehman A. Dyslipidemia. Treasure Island (FL): StatPearls Publishing; 2025.