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The Effect of P-Cymene on Glucose, Insulin, Antioxidant Power, and the Level of AKT Gene mRNA in Streptozotocin-Induced Diabetes Model in Male Wistar Rats
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Maryam Arabloei Sani1    , Zahra Hajebrahimi2 , Parichehreh Yaghmaei1 , Nasim Hayati Roodbari1 |
1- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
2- Aerospace Research Institute, Ministry of Science Research and Technology, Tehran, Iran , hajebrahimi@ari.ac.ir |
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Abstract: (889 Views) |
Background and Aim: Diabetes is a main metabolic disorder in middle-aged and older people. Oxidative stress can interfere with insulin signaling and are directly relevant to the incidence of diabetes. The AKT signaling pathways plays a critical role in regulating glucose homeostasis and proliferation of β cells. P-cymene is an aromatic monotropene with antioxidant and anti-inflammatory properties. In the present study, the therapeutic effects of p-cymene on blood glucose and insulin levels, the antioxidant power of serum (FRAP assay) and the expression of AKT mRNAs in streptozotocin-induced diabetic rats were investigated.
Materials and Methods: Diabetes was induced using the injection of 55 mg/kg streptozotocin in male Wistar rats. Histological, biochemical, and real-time PCR analyses were done to study the effects of metformin (55 mg/kg) and p-cymene (25, 50, and 100 mg/kg) on levels of glucose, insulin, oxidative stress status, and the expression of AKT mRNA.
Results: Streptozotocin increased serum levels of glucose and decreased serum levels of insulin, the antioxidant power of serum, pancreas levels of AKT mRNA, and β island size. Administration of metformin or p-cymene improved the levels of glucose, insulin, AKT mRNA, β island size, and antioxidant power in an independent manner of dose.
Conclusion: These results suggest that p-cymene has hypoglycemic, hyperinsulinemia, and antioxidant properties. It can regulate Akt signaling pathway. Therefore, it may be suggested for the diabetes therapy alone or in combination with metformin.
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| Keywords: Diabetes Mellitus, P-Cymene, Oxidative Stress, AKT |
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Full-Text [PDF 676 kb]
(214 Downloads)
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Type of Study: Original Research |
Subject:
Pharmacology
Received: 2024/01/17 | Accepted: 2024/05/26 | Published: 2024/12/29
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1. Murea M, Ma L, Freedman BI. Genetic and environmental factors associated with type 2 diabetes and diabetic vascular complications. Rev Diabet Stud. 2012;9(1):6-22. [ DOI:10.1900/RDS.2012.9.6] [ PMID] [ ] 2. Oguntibeju OO. Type 2 diabetes mellitus, oxidative stress and inflammation: examining the links. IJPPP. 2019;11(3):45-63. 3. Abeyrathna P, Su Y. The critical role of Akt in cardiovascular function. Curr. Vasc. Pharmacol.2015;74:38-48. [ DOI:10.1016/j.vph.2015.05.008] [ PMID] [ ] 4. Zdychová J, Komers R. Emerging role of Akt kinase/protein kinase B signaling in pathophysiology of diabetes and its complications. Physiol Res. 2005;54:1. [ DOI:10.33549/physiolres.930582] [ PMID] 5. Bernal-Mizrachi E, Wen W, Stahlhut S, Welling CM, Permutt MA. Islet beta cell expression of constitutively active Akt1/PKB alpha induces striking hypertrophy, hyperplasia, and hyperinsulinemia. J Clin Invest. 2001;108(11):1631-8. [ DOI:10.1172/JCI200113785] [ PMID] [ ] 6. Jiang ZY, Zhou QL, Coleman KA, Chouinard M, Boese Q, Czech MP. Insulin signaling through akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing. PNAS. 2003;100:7569-74. [ DOI:10.1073/pnas.1332633100] [ PMID] [ ] 7. Beg M, Abdullah N, Thowfeik FS, Altorki NK, McGraw TE. Distinct Akt phosphorylation states are required for insulin regulated Glut4 and Glut1-mediated glucose uptake. eLife. 2017;6:e26896. [ DOI:10.7554/eLife.26896] [ PMID] [ ] 8. De Oliveira TM, de Carvalho RBF, da Costa IHF, de Oliveira GAL, de Souza AA, de Lima SG, et al. Evaluation of p-cymene, a natural antioxidant. Pharm Bio. 2015;53:423-8. [ DOI:10.3109/13880209.2014.923003] [ PMID] 9. Quintans-Júnior L, Moreira JC, Pasquali MA, Rabie SM, Pires AS, Schröder R, et al. Antinociceptive Activity and Redox Profile of the Monoterpenes (+)-Camphene, p-Cymene, and Geranyl Acetate in Experimental Models. ISRN Toxicol. 2013;2013:459530. [ DOI:10.1155/2013/459530] [ PMID] [ ] 10. Haribabu J, Ranade DS, Bhuvanesh NSP, Kulkarni PP, Karvembu R. Ru(II)-p-cymene thiosemicarbazone complexes as inhibitors of amyloid β (Aβ) peptide aggregation and Aβ-induced cytotoxicity. Chemistry Select. 2017;2(35):11638-44. [ DOI:10.1002/slct.201702390] 11. Seifi-Nahavandi B, Yaghmaei P, Ahmadian S, Ghobeh M, Ebrahim-Habibi A. Cymene consumption and physical activity effect in Alzheimer's disease model: an in vivo and in vitro study. J Diabetes Metab Disord. 2020;19(2):1381-89. [ DOI:10.1007/s40200-020-00658-2] [ PMID] [ ] 12. Wang S, Wang X, Wang Y, Leng Q, Sun Y, Hoffman RM, eta al. The Anti-oxidant Monoterpene p-Cymene Reduced the Occurrence of Colorectal Cancer in a Hyperlipidemia Rat Model by Reducing Oxidative Stress and Expression of Inflammatory Cytokines. Anticancer Res. 2021;41(3):1213-18. [ DOI:10.21873/anticanres.14878] [ PMID] 13. Rahimpour P, Sheikholeslami-Vatani D, Moloudi M, Ghaeeni S. The effect of training type on the signaling Pathway of ceramide-dependent insulin resistance in the flexor hallucis longus muscle of streptozotocin-induced diabetic rats. Cell J. 2023;25(7):461-9. 14. de Oliveira TM, de Carvalho RBF, da Costa IHF, de Oliveira GAL, de Souza AA, de Lima SG, et al. Evaluation of p-cymene, a natural antioxidant. Pharm Biol. 2015;53(3):423-8. [ DOI:10.3109/13880209.2014.923003] [ PMID] 15. Lotfi P, Yaghmaei P, Ebrahim-Habibi A. Cymene and Metformin treatment effect on biochemical parameters of male NMRI mice fed with high fat diet. J Diabetes Metab Disord. 2015;14:52. [ DOI:10.1186/s40200-015-0182-x] [ PMID] [ ] 16. Poorgholam P, Yaghmaei P, Noureddini M, Hajebrahimi Z. Effects of artemisinin and TSP‑1‑human endometrial‑derived stem cells on a streptozocin‑induced model of Alzheimer's disease and diabetes in Wistar rats. Acta Neurobiol Exp. 2021;81(2):141-150. [ DOI:10.21307/ane-2021-013] 17. Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of"antioxidant power": the FRAP assay. Anal Biochem. 1996;239(1):70-6. [ DOI:10.1006/abio.1996.0292] [ PMID] 18. Ahmadi A, Vahabzadeh Z, Moloudi M, Farhadi L, Shirahmadi S. Contribution of toll-like receptor 2 and nicotinamide adenine dinucleotide phosphate oxidase to the trimethylamine N-oxide-induced inflammatory reactions in U937-derived macrophages. ARYA Atheroscler. 2021;17:2096. 19. Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia. 2008;51(2):216-26. [ DOI:10.1007/s00125-007-0886-7] [ PMID] 20. Nukatsuka M, Yoshimura Y, Nishida M, Kawada J. Allopurinol protects pancreatic beta cells from the cytotoxic effect of streptozotocin: in vitro study. J Pharmacobiodyn. 1990;13:259-62. [ DOI:10.1248/bpb1978.13.259] [ PMID] 21. Nogueira-Machado JA, Chaves MM. From hyperglycemia to AGE-RAGE interaction on the cell surface: a dangerous metabolic route for diabetic patients. Expert Opin Ther Targets. 2008;12:871-82. [ DOI:10.1517/14728222.12.7.871] [ PMID] 22. Rong Y, McPhee C K, Deng S, Huang L, Chen L, Liu M, et al. Spinster is required for autophagic lysosome reformation and mTOR reactivation following starvation. Proc Natl Acad Sci USA 2011;108(19):7826-31. [ DOI:10.1073/pnas.1013800108] [ PMID] [ ] 23. Chetram MA, Bethea DA, Jones KJ, Don-Salu-Hewage AS, Odero-Marah VA, Hinton CV. ROS-mediated activation of AKT induces apoptosis via pVHL in prostate cancer cells. Mol Cell Biochem. 2013;376(1-2):63-71. [ DOI:10.1007/s11010-012-1549-7] [ PMID] [ ] 24. Wen C, Wang H, Wu X, He L, Zhou Q, Wang F, et al. ROS-mediated inactivation of the PI3K/AKT pathway is involved in the antigastric cancer effects of thioredoxin reductase-1 inhibitor chaetocin. Cell Death Dis. 2019;10(11):809. [ DOI:10.1038/s41419-019-2035-x] [ PMID] [ ] 25. Li X, Song D, Leng SX. Link between type 2 diabetes and Alzheimer's disease: from epidemiology to mechanism and treatment. Clin Interv Aging. 2015;10:549-60. [ DOI:10.2147/CIA.S74042] [ PMID] [ ] 26. Balcazar N, Sathyamurthy A, Elghazi L, Gould A, Weiss A, Shiojima I, et al. mTORC1 activation regulatesbeta-cell mass and proliferation by modulation of cyclin D2 synthesis andstability. J Biol Chem. 2009;284:7832-42. [ DOI:10.1074/jbc.M807458200] [ PMID] [ ] 27. Stamateris RE, Sharma RB, Kong Y, Ebrahimpour P, Panday D, Ranganath P, et al. Glucose induces mouse b-cell proliferation via IRS2, MTOR, and cyclin D2 but not the insulin receptor. Diabetes. 2016;65:981-95. [ DOI:10.2337/db15-0529] [ PMID] [ ] |
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Research code: -- Ethics code: IR.IAU.SRB.REC.1396.168
Arabloei Sani M, Hajebrahimi Z, Yaghmaei P, Hayati Roodbari N. The Effect of P-Cymene on Glucose, Insulin, Antioxidant Power, and the Level of AKT Gene mRNA in Streptozotocin-Induced Diabetes Model in Male Wistar Rats. SJKU 2024; 29 (5) :25-36 URL: http://sjku.muk.ac.ir/article-1-8288-en.html
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