Tempeh-Based Supplement Decreases Blood Glucose Levels Through Inhibiting Rage and NF-κB Activity in Type 2 Diabetes Mellitus Mice Model
DOI:
https://doi.org/10.31584/jhsmr.20241056Keywords:
diabetes mellitus, NF-κB, RAGE, TBS, tempehAbstract
Objective: Hyperglycemia promotes inflammation through inducing the formation of AGE products, which bind with receptor AGE (RAGE) products in cell membranes, leading to the activation of necrosis factor–kappa beta (NF-κB). This study aimed to analyze the effects of tempeh-based supplement (TBS) preparations of γ-amino butyric acid (GABA) tempeh against mRNA expressions of RAGE and NF-κB on the pancreas of a type 2 diabetes mellitus (DM) mice model.
Material and Methods: This research was a quasi-experiment, with pre and post-tests with a control design for blood glucose levels; and post-test only utilizing control for mRNA RAGE and NF-κB expressions. A total of 30 male mice, 8-10 weeks old, weighing 20-25 g were divided into 6 treatment groups: non-diabetic, Diabetic, Diabetic+metformin, Diabetic+TBS 10 mg/100 g BW, Diabetic+TBS 20 mg/100 g BW, and Diabetic+TBS 40 mg/100 g BW. STZ induction once a day for two days was preceded by NA to create a DM mice model; meanwhile, TBS was administrated once a day for 21 days.
Results: The mean difference of fasting glucose levels in the diabetic+TBS 40 mg/100 g BW group was the highest when compared to the diabetic group (159.52±1.85) mg/dL. One-way ANOVA revealed statistically significant differences in fasting glucose levels, RAGE and NF-κB expressions in the Diabetic+TBS group at various dosage levels compared to the diabetic control group. Relative mRNA expressions of RAGE and NF-κB were downregulated in the treatment group compared to the diabetic control group.
Conclusion: TBS can decrease fasting blood glucose levels and downregulate relative mRNA expressions of RAGE and NF-κB in type 2 DM mice.
References
da Rocha Fernandes J, Ogurtsova K, Linnenkamp U, Guariguata L, Seuring T, Zhang P, et al. IDF diabetes atlas estimates of 2014 global health expenditures on diabetes. Diabetes Res Clin Pract 2016;117:48-54. doi: 10.1016/j.diabres.2016.04.016.
Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, et al. IDF diabetes atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 2018;138:271-81. doi: 10.1016/j.diabres.2018.02.023.
Khan IA, Jahan P, Hasan Q, Rao P. Genetic confirmation of T2DM meta-analysis variants studied in gestational diabetes mellitus in an Indian population. Diabetes Metab Syndr 2019;13:688-94. doi: 10.1016/j.dsx.2018.11.035.
Kumar MP, Mamidala E, Al-Ghanim KA, Al-Misned F, Mahboob S. Evaluation of the andrographolides role and its indoleamine 2,3-dioxygenase inhibitory potential and attendant molecular mechanism against STZ-induced diabetic rats. Saudi J Biol Sci 2020;27:713-9. doi: 10.1016/j.sjbs.2019.12.007.
American Diabetes Association. Classification and diagnosis of diabetes: standards of medical care in diabetes-2020. Diabetes Care 2020;43:S14-31. doi: 10.2337/dc20-S002.
Landon R, Gueguen V, Petite H, Letourneur D, Pavon-Djavid G, Anagnostou F. Impact of astaxanthin on diabetes pathogenesis and chronic complications. Mar Drugs 2020;18. doi: 10.3390/md18070357.
Liu Y, Qu Y, Wang R, Ma Y, Xia C, Gao C, et al. The alternative crosstalk between RAGE and nitrative thioredoxin inactivation during diabetic myocardial ischemia-reperfusion injury. Am J Physiol Endocrinol Metab 2012;303:E841-52. doi: 10.1152/ajpendo.00075.2012.
Patel S, Santani D. Role of NF-kappa B in the pathogenesis of diabetes and its associated complications. Pharmacol Rep 2009;61:595-603. doi: 10.1016/s1734-1140(09)70111-2.
Rameshwar P, Narayanan R, Qian J, Denny TN, Colon C, Gascon P. NF-kappa B as a central mediator in the induction of TGF-beta in monocytes from patients with idiopathic myelofibrosis: an inflammatory response beyond the realm of homeostasis. J Immunol 2000;165:2271-7. doi: 10.4049/jimmunol.165.4.2271.
Suryavanshi SV, Kulkarni YA. NF-κB: a potential target in the management of vascular complications of diabetes. Front Pharmacol 2017;8:798. doi: 10.3389/fphar.2017.00798.
Ysrafil Y, Sapiun Z, Slamet NS, Mohamad F, Hartati H, Damiti SA, et al. Anti-inflammatory activities of flavonoid derivates. Admet dmpk 2023;11:331-59. doi: 10.5599/admet.1918.
Liu D, Zhen W, Yang Z, Carter JD, Si H, Reynolds KA. Genistein acutely stimulates insulin secretion in pancreatic beta-cells through a cAMP-dependent protein kinase pathway. Diabetes 2006;55:1043-50. doi: 10.2337/diabetes.55.04.06.db05-1089.
Prud’homme GJ, Glinka Y, Udovyk O, Hasilo C, Paraskevas S, Wang Q. GABA protects pancreatic beta cells against apoptosis by increasing SIRT1 expression and activity. Biochem Biophys Res Commun 2014;452:649-54. doi: 10.1016/j.bbrc.2014.08.135.
Esaki H, Onozaki H, Kawakishi S, Osawa T. New antioxidant isolated from tempeh. J Agric Food Chem 1996;44:696-700. doi: 10.1021/jf950454t.
Kim EK, Kwon KB, Song MY, Seo SW, Park SJ, Ka SO, et al. Genistein protects pancreatic beta cells against cytokine-mediated toxicity. Mol Cell Endocrinol 2007;278:18-28. doi: 10.1016/j.mce.2007.08.003.
Watanabe N, Fujimoto K, Aoki H. Antioxidant activities of the water-soluble fraction in tempeh-like fermented soybean (GABA-tempeh). Int J Food Sci Nutr 2007;58:577-87. doi: 10.1080/09637480701343846.
Mohd Yusof H, Ali NM, Yeap SK, Ho WY, Beh BK, Koh SP, et al. Hepatoprotective effect of fermented soybean (nutrient enriched soybean tempeh) against alcohol-induced liver damage in mice. Evid Based Complement Alternat Med 2013;2013:274274. doi: 10.1155/2013/274274.
Hwang JH, Wu SJ, Wu PL, Shih YY, Chan YC. Neuroprotective effect of tempeh against lipopolysaccharide-induced damage in BV-2 microglial cells. Nutr Neurosci 2019;22:840-9. doi: 10.1080/1028415x.2018.1456040.
Aoki H, Uda I, Tagami K, Furuya Y, Endo Y, Fujimoto K. The production of a new tempeh-like fermented soybean containing a high level of gamma-aminobutyric acid by anaerobic incubation with Rhizopus. Biosci Biotechnol Biochem 2003;67:1018-23. doi: 10.1271/bbb.67.1018.
Saono S, Hull RR, Dhamcharee B. Concise handbook of indigenous fermented foods in the ASCA countries. Jakarta, Indonesia: indonesian institute of sciences; 1986.
Aoki H, Furuya Y, Endo Y, Fujimoto K. Effect of gamma-aminobutyric acid-enriched tempeh-like fermented soybean (GABA-Tempeh) on the blood pressure of spontaneously hypertensive rats. Biosci Biotechnol Biochem 2003;67:1806-8. doi: 10.1271/bbb.67.1806.
Ito M, Ito T, Aoki H, Nishioka K, Shiokawa T, Tada H, et al. Isolation and identification of the antimicrobial substance included in tempeh using Rhizopus stolonifer NBRC 30816 for fermentation. Int J Food Microbiol 2020;325:108645. doi: 10.1016/j.ijfoodmicro.2020.108645.
Nistiar F, Racz O, Lukacinova A, Hubkova B, Novakova J, Lovasova E, et al. Age dependency on some physiological and biochemical parameters of male wistar rats in controlled environment. J Environ Sci Health A Tox Hazard Subst Environ Eng 2012;47:1224-33. doi: 10.1080/10934529.2012.672071.
Bathina S, Gundala NKV, Rhenghachar P, Polavarapu S, Hari AD, Sadananda M, et al. Resolvin D1 ameliorates nicotinamide-streptozotocin-induced type 2 diabetes mellitus by its anti-inflammatory action and modulating PI3K/Akt/mTOR pathway in the brain. Arch Med Res 2020;51:492-503. doi: 10.1016/j.arcmed.2020.05.002.
Zhu L, Sha L, Li K, Wang Z, Wang T, Li Y, et al. Dietary flaxseed oil rich in omega-3 suppresses severity of type 2 diabetes mellitus via anti-inflammation and modulating gut microbiota in rats. Lipids Health Dis 2020;19:20. doi: 10.1186/s12944-019-1167-4.
Chen YX, Fang CF, Wang X, Nie RQ, Li G, Tang L, et al. Glucometabolic state of in-hospital primary hypertension patients with normal fasting blood glucose in a sub-population of China. Diabetes Metab Res Rev 2009;25:357-62. doi: 10.1002/dmrr.950.
Stephanie T, Kartawidjajaputra F, Silo W, Yogiara Y, Suwanto A. Tempeh consumption enhanced beneficial bacteria in the human gut. Food Res 2019;3:57-63. doi: 10.26656/fr.2017.3(1).230.
Baú TR, Garcia S, Ida EI. Changes in soymilk during fermentation with kefir culture: oligosaccharides hydrolysis and isoflavone aglycone production. Int J Food Sci Nutr 2015;66:845-50. doi: 10.3109/09637486.2015.1095861.
Cao ZH, Green-Johnson JM, Buckley ND, Lin QY. Bioactivity of soy-based fermented foods: a review. Biotechnol Adv 2019;37:223-38. doi: 10.1016/j.biotechadv.2018.12.001.
Dao MC, Everard A, Aron-Wisnewsky J, Sokolovska N, Prifti E, Verger EO, et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut 2016;65:426-36. doi: 10.1136/gutjnl-2014-308778.
Li J, Yang G, Zhang Q, Liu Z, Jiang X, Xin Y. Function of akkermansia muciniphila in type 2 diabetes and related diseases. Front Microbiol 2023;14:1172400. doi: 10.3389/fmicb.2023.1172400.
Blaschke F, Takata Y, Caglayan E, Law RE, Hsueh WA. Obesity, peroxisome proliferator-activated receptor, and atherosclerosis in type 2 diabetes. Arterioscler Thromb Vasc Biol 2006;26:28-40. doi: 10.1161/01.Atv.0000191663.12164.77.
Sanjiwani MID, Aryadi IPH, Semadi IMS. Review of literature on akkermansia muciniphila and its possible role in the etiopathogenesis and therapy of type 2 diabetes mellitus. J ASEAN Fed Endocr Soc 2022;37:69-74. doi: 10.15605/jafes.037.01.13.
Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia 2017;60:1577-85. doi: 10.1007/s00125-017-4342-z.
Zhou Z, Tang Y, Jin X, Chen C, Lu Y, Liu L, et al. Metformin inhibits advanced glycation end products-induced inflammatory response in murine macrophages partly through AMPK activation and RAGE/NFκB pathway suppression. J Diabetes Res 2016;2016:4847812. doi: 10.1155/2016/4847812.
Tian J, Dang HN, Yong J, Chui WS, Dizon MP, Yaw CK, et al. Oral treatment with γ-aminobutyric acid improves glucose tolerance and insulin sensitivity by inhibiting inflammation in high fat diet-fed mice. PLoS One 2011;6:e25338. doi: 10.1371/journal.pone.0025338.
Palanisamy N, Kannappan S, Anuradha CV. Genistein modulates NF-κB-associated renal inflammation, fibrosis and podocyte abnormalities in fructose-fed rats. Eur J Pharmacol 2011;667:355-64. doi: 10.1016/j.ejphar.2011.06.011.
Lu MP, Wang R, Song X, Chibbar R, Wang X, Wu L, et al. Dietary soy isoflavones increase insulin secretion and prevent the development of diabetic cataracts in streptozotocin-induced diabetic rats. Nutr Res 2008;28:464-71. doi: 10.1016/j.nutres.2008.03.009.
Liu Y, Liang C, Liu X, Liao B, Pan X, Ren Y, et al. AGEs increased migration and inflammatory responses of adventitial fibroblasts via RAGE, MAPK and NF-kappaB pathways. Atherosclerosis 2010;208:34-42. doi: 10.1016/j.atherosclerosis.2009.06.007.
Vlassara H. The AGE-receptor in the pathogenesis of diabetic complications. Diabetes Metab Res Rev 2001;17:436-43. doi: 10.1002/dmrr.233.
Stokes SE, Winn LM. NF-κB signaling is increased in HD3 cells following exposure to 1,4-benzoquinone: role of reactive oxygen species and p38-MAPK. Toxicol Sci 2014;137:303-10. doi: 10.1093/toxsci/kft256.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.