اثر اولئوروپین بر میزان گلوکز خون و بیان ژن پیروات کیناز در موش های صحرایی نر دیابتی شده با استرپتوزوتوسین
اثر اولئوروپین بر گلوکز خون و ژن پیروات کیناز در موش های صحرایی دیابتی
محورهای موضوعی : نشانگر های زیستی پلاسما
اکرم اسدی
1
,
مریم رفیعی راد
2
,
آمنه جاوید
3
1 - علم و هنر یزد
2 - گروه زیست شناسی دانشگاه آزاد اسلامی واحد ایذه
3 - گروه زیست شناسی دانشکده مهندسی و علوم دانشگاه علم و هنر یزد
کلید واژه: دیابت, اولئوروپین, پیروات کیناز, موش صحرایی,
چکیده مقاله :
زمینه و هدف: با توجه به خواص آنتی اکسیدانی اولئوروپین و نقش آنتی اکسیدان ها در بهبود دیابت، این مطالعه با هـدف بررسی اثر اولئوروپین بر میزان گلوکز خون و بیان ژن پیروات کیناز در موش های صحرایی نر دیابتی انجام شد. مواد و روش ها : با تزریق استرپتوزوتوسین (mg/kg60) در موش هاي صحرایی نر (250-200گرم) دیابت ایجـاد شـد. ح پس از تزریق داخل صفاقی STZ، حیوانات دارای قند خون بالای 200mg/dL، دیابتی تلقی شدند. گروه‌های کنترل و گروه دیابتی فقط سالین و گروه‌های دیابتی درمان شده به مدت چهار هفته روزانه بصورت گاواژ اولئوروپین mg/kg 10،20دریافت کردند. سپس رت ها با دارو بی هوش و تشریح شدند. بافت کبد جداسازی و برای بررسی بیان ژن پیروات کیناز به روش Real-time PCR استفاده شد. تجزیه و تحلیل داده‌ها با استفاده از آزمون توکی در سطح P<0.05 انجام شد. نتایج : نتایج نشان داد در گروه دیابتی دریافت کننده دوزهای mg/kg 20و10 اولئوروپین نسبت به گروه دیابتی به طور معناداری کاهش یافت. بررسی بیان ژن پیروات کیناز نیز نـشان داد در گروه دیابتی ﻧﺴﺒﺖ ﺑﻪ گروه کنترل ﺳﺎﻟﻢ ﺩﺍﺭﺍﻱ کاهش ﺑﻮﺩ ﺍﻣﺎ ﺍﻳﻦ کاهش ﺍﺯ ﻧﻈﺮ ﺁﻣﺎﺭﻱ ﺩﺭ ﺣﺪ ﻣﻌﻨﻲﺩﺍﺭﻱ ﺑﻴﺎﻥ ﻧﺸﺪ. از طرفی ﺩﺭ گروه دیابتی تحت درمان با دوز های mg/kg 20 و 10 اولئوروپین میزان بیان ژن پیروات کیناز نسبت به گروه دیابتی به طور معناداری افزایش داشته است. نتیجه گیری: نتایج تحقیق حاضر نشان می دهد که احتمالا تجویز اولئوروپین توانسته از طریق تغییر میزان بیان ژن پیرووات کیناز باعث کاهش گلوکز خون شود
Background & Aim: Considering the antioxidant properties of oleuropein and the role of antioxidants in improving diabetes, this study was conducted with the aim of investigating the effect of oleuropein on blood glucose levels and pyruvate kinase gene expression in diabetic male rats. Materials & Methods: 40 rats aged 2-3 months (weighing 200-250 grams) were divided into four groups of ten. By injecting streptozotocin (60 mg/kg), type 1 diabetes was induced in male rats. After intraperitoneal injection of STZ, animals with blood glucose above 200 mg/kg were considered diabetic. The control groups and the diabetic group only received saline and the treated diabetic groups received 10, 20 mg/kg oleuropein daily by gavage for four weeks. At the end of the experiment period, all the rats were dissected after anesthesia with ether by drawing blood from the heart and liver tissue was isolated and used to check the expression of pyruvate kinase gene by Real-time PCR method. Data analysis was performed using Tukey's test at P<0.05 level. Results: The results showed that in the diabetic group receiving doses of 10 and 20 mg/kg of oleuropein, the blood glucose level decreased significantly compared to the diabetic group. Examining the expression of pyruvate kinase gene also showed that there was a decrease in the diabetic group compared to the healthy control group, but this decrease was not statistically significant. On the other hand, in the diabetic group treated with 20 and 10 mg/kg doses of oleuropein, pyruvate kinase gene expression increased significantly compared to the diabetic group. Conclusion: The results of the present study showed that the administration of oleuropein has been able to reduce blood glucose by changing the expression of the pyruvate kinase gene.
1.Risbridger G, Wang H, Young P, Kurita T,Wang YZ, Lubahn D, et al. Evidences That Epithelial And Mesenchymal Estrogen ReceptorAlpha Mediates Effects Of Estrogen On Prostatic Epithelium. Dev Biol .2001; 229(2): 432-42. 2. Karabag-Coban F, Hazman O, Bozkurt MF, Ince S. Antioxidant Status And Anti-Inflammatory Effects Of Oleuropein In Streptozotocin-Induced Diabetic Nephropathy In Rats. Eur J Med Plants. 2017; 18(2): 1-10. 3.Jemai H, Sayadi S. Heart Histopathology And Oxidative Features In Diabetic Rats And Protective Effects Of Oleuropein. Advances in Bioscience and Biotechnology .2015; 6(6): 383-9. 4.Meyer K, Deutscher J, Anil M, Berthold A, Bartsch G, Kiess W. Serum Androgen Levels In Adolescents With Type I Diabetes: Relationship To Pubertal Stage And Metabolic Control. J Endocrinol Invest. 2000; 23: 362-8. 5.Kumar S, Malhotra R, Kumar D. Antidiabetic And Free Radical Scavenging Potential Of Euphorbia Hirta Flower Extract. Indian J Pharm Sci .2010; 72(4): 533-7. 6. Wooll JO, Friesen RHE, White MA, Watowich SJ, Fox RO, Ching Lee J, et al. Structural and functional linkages between subunit interfaces in mammalian pyruvate kinase. Journal of Molecular Biology 2001; 312: 525- 40. 7. Noguchi R, Yamada K, Inove H, Matsuda T, Tanaka T. The L-and R-type isozymes of rat pyruvate kinase are produced from a single gene by use a different promoters. The Journal of Biological Chemistry 1987; 262(29): 14366- 71. 8. Noguchi T, Inove H, Tanaka T. The M1-and M2-type isozymes of rat pyruvate kinase are produced from the same gene by alternative RNA splicing. The Journal of Biological Chemistry 1986; 261(29): 13807-12. 9.Omar SH. Oleuropein in olive and its pharmacological effects. Sci Pharm 2010;78(2):133-54. 10.Al Jamal AR, Ibrahim A Effects Of Olive Oil On Lipid Profiles And Blood Glucose In Type2 Diabetic Patients. Int J Diabetes Metab 2011; 19:19-22. 11. Anup KM, Smriti T, Zabeer A, Ram KS.Antidiabetic and antihhyperlipidemic effect of Euphorbia hirta in Streptozotocin induced diabetic rats. Scholars Research Library. 2012;4(2):703-7. 12. Özlem S, Aslan T, Tülay AÇ. Antioxidant, cytotoxic and apoptotic activities of extracts from medicinal plant Euphorbia platyphyllos L. Journal of Medicinal Plants Research. 2013;7(19):1293-304. 13.Anup KM, Smriti T, Zabeer A, Ram K S. Antidiabetic and antihhyperlipidemic effect of Euphorbia hirta in Streptozotocin induced diabetic rats. Scholars Research Library 2012; 4 (2):703-7. 14. Omar SH. Oleuropein in olive and its pharmacological effects. Science Pharmacology.2010;30;78(2):133-54. 15.Lee OH, Lee BY, Lee J, Lee HB, Son JY, Park CS, et al. Assessment of phenolics-enriched extract and fractions of olive leaves and their antioxidant activities. Bioresource Technology.2009;100(23):6107-13. 16. Omar SH. Cardio protective and neuroprotective roles of oleuropein in olive. Saudi Pharmaceutical Journal. 2011;18(3):111-21. 17.Nediani C, Ruzzolini J, Romani A, Calorini L.Oleuropein, a Bioactive Compound from Olea europaea L., as a potential preventive and therapeutic agent in non-communicable diseases.Antioxidants. 2019;8(12):578. 18. Karabag-Coban F, Hazman O, Bozkurt MF, Ince S. Antioxidant status and anti-inflammatory effects of oleuropein in Streptozotocin-induced diabetic nephropathy in rats. European Journal of Medicinal Plants. 2017;18(2):1-10. 19.Ahmadvand H, Noori A, Ghasemi Dehnoo M, Bagheri S, Cheraghi R. Hypoglycemic, hypolipidemic and antiatherogenic effects of oleuropein in alloxan-induced type 1 diabetic rats. Asian Pacific Journal of Tropical Disease. 2014;4(1):421-25. 20. Karabag-Coban F, Hazman O, Bozkurt MF, Ince S. Antioxidant status and anti-inflammatory effects of oleuropein in Streptozotocin-induced diabetic nephropathy in rats. European Journal of Medicinal Plants. 2017;18(2):1-10. 21. Rafieirad M, Abdolhassan Doulah AH, Goudarzi S. Evaluation of the Effect of Alpha-pinene on Blood Glucose and Lipid Profiles, in Diabetic Rats. Journal of Animal Biology.2022; 14(3): 171-180. 22.Ghasemzadeh Dehkordi S, Doulah A, Rafieirad M. The Effect of Four Weeks Swimming Practice and Oleuropin Supplementation on Memory Impairment and Parkinson's Pain in Adult Male Rats. The Quarterly Journal of Applied Biology.2022;35(1):180-195. 180-195. 23.Darvish Sargazi M, Sabbagh S, Miri H R, Najafi S, Sabbagh K. The effect of hydro-alcoholic Prosopis farcta fruit extract on blood glucose and gene expression of pyruvate kinase in type 1 diabetic rats. yafte 2016; 17 (4) :54-61. 24.Can A, Akev N, Ozsoy N, Bolkent S, Arda BP, Yanardag R, et al. Effect of Aloe vera leaf gel and pulp extracts on the liver in type-II diabetic rat models. Biological and Pharmaceutical Bulletin.2004; 27(5): 694-8. 25.Chahardoli M, Mahmoodi M, Hajizadeh M, Khoramdel Azad H, Khoshdel A, Mirzaei M. Effect of Aloe Vera Hydroalcoholic Extract on Blood Glucose, Serum Insulin and the Key Enzymes in Metabolic Pathways of Glycolysis and Gluconeogenesis in Hepatocytes of Type 1 Diabetic Rats. JRUMS.2015; 13 (8) :669-682. 26.Zhang X, Yang S, Chen J, Su Z.Unraveling the regulation of hepatic gluconeogenesis. Front Endocrinol.2019; 9: 802. 27.Biyani MK, Banavalikar MM, Suthar AC, Shahani S, Sivakami S, Vidri J. Antihyperglycemic effects of three extract from momoridaca charantia. Journal of Ethnopharmocology.2003; 88: 107-11. 28. Rajala A, Soni K, Rajala RVS. Metabolic and Non-metabolic Roles of Pyruvate Kinase M2 Isoform in Diabetic Retinopathy. Sci Rep. 2020 May 4;10(1):7456. 29- Lee IK. The role of pyruvate dehydrogenase kinase in diabetes and obesity. Diabetes Metab J. 2014 Jun;38(3):181-6. 30-Can A, Akev N, Ozsoy N, Bolkent S, Arda BP, Yanardag R, et al. Effect of Aloe vera leaf gel and pulp extracts on the liver in type-II diabetic rat models. Biological and Pharmaceutical Bulletin.2004;27(5): 694-8. 31- Yeylaghi Ashrafi MR, Abednatanzi H, Ghazalian F. The effect of eight weeks of high intensity interval training and nchromosomal royal jelly on G6Pase gene expression in hepatocytes, glucose levels and insulin resistance in type 2 diabetic rats.RJMS 2020; 27(8): 135-150 (Persian). 32- Haeusler RA, Camastra S, Astiarraga B, Nannipieri M, Anselmino M, Ferrannini E. Decreased expression of hepatic glucokinase in type 2 diabetes. Mol Metabol. 2015;4(3):222-6. 33- Rui L. Energy metabolism in the liver. Comprehen Physiol. 2014;4(1):177-97. 34-Postic C, Dentin R, Girard J. Role of the liver in the control of carbohydrate and lipid homeostasis. Diabetes Metab. 2004;30(5): 398-408. 35-Rahimi N, Delfan B, Motamed-Gorji N, Dehpour AR. Effects of oleuropein on pentylenetetrazol-induced seizures in mice: involvement of opioidergic and nitrergic systems. J Nat .2017;71(2):389-96. 36- Pourkhodadad S, Alirezaei M, Moghaddasi M, Ahmadvand H, Karami M, Delfan B, et al. Neuroprotective effects of oleuropein against cognitive dysfunction induced by colchicine in hippocampal CA1 area in rats .J Physiol Sci. 2016 Sep;66(5):397-405. 37.Rahimi N, Delfan B, Motamed-Gorji N, Dehpour AR. Effects of oleuropein on pentylenetetrazol-induced seizures in mice: involvement of opioidergic and nitrergic systems. J Nat .2017;71(2):389-96. 38.Dekanski D, Selaković V, Piperski V, Radulović Ž, Korenić A, Radenović L. Protective effect of olive leaf extract on hippocampal injury induced by transient global cerebral ischemia and reperfusion in Mongolian gerbils. Phytomedicine.2011;18(13):1137-43. 39.De La Cruz JP, Del Río S, Arrebola MM, López-Villodres JA, Jebrouni N, González-Correa JA. Effect of virgin olive oil plus acetylsalicylic acid on brain slices damage after hypoxia-reoxygenation in rats with type 1-like diabetes mellitus. Neurosci Lett.2010; 471(2):89-93. 40. Kuem N, Song SJ, Yu R, Yun JW, Park T. Oleuropein attenuates visceral adiposity in high‐fat diet‐induced obese mice through the modulation of WNT10b‐and galanin‐mediated signaling. Mol Nutr Food Res. 2014;58(11):2166-76. 41. Khalatbary AR, Ghaffari E, Mohammadnegad B. Protective role of oleuropein against acute deltamethrin-induced neurotoxicity in rat brain. Iran Biomed .2015;19(4):247-53. 42.Khalatbary AL. Olive oil phenols and neuroprotection. Nutr Neurosci. 2013;16(6):243-9. 43. Barzin M, Hosseinpanah F, Arzhan S, Azizi F. Trends of obesity and abdominal obesity in Tehranian adults. Pajoohandeh Journal.2011; 16(5):212-8. (In Persian) 44.Janghorbani M, Amini M, Willett WC, Gouya MM, Delavari A, Alikhani S, et al. First nationwide survey of prevalence of overweight, underweight, and abdominal obesity in Iranian adults. Obesity.2007;15(11):2797-808. 45.Mahmoodi M, Hosseini-Zijoud SM, Kazemi Arababadi M, Khorramdelazad H. Effect of Persian shallot (Allium hirtifolium Boiss. extract on glucokinase (GCK), glycogen phosphorylase and phosphoenolpyruvate carboxykinase (PEPCK) genes expression in diabetic rats. African J Pharmacy and Pharmacol 2013; 7(7): 389-96. 46. Hosseini-Zijoud SM, Mahmoodi M. The effects of Persian shallot extract on the levels of some blood biochemical parameters in streptozotocin-induced diabetic rats. African Journal of Agricultural Research 2012; 7(22): 3308-13. 47. Nazari M, Hajizadeh MR, Mahmoodi M, Mirzaei MR, Hassanshahi G. The regulatory impacts of Morus Alba leaf extract on some enzymes involved in glucosemetabolism pathways in diabetic rat liver. Clin Lab 2012; 59(5-6): 497-504. 48.Bazi Shad A, Miri H R, Esmaeilzadeh Bahabadi S, Hajinezhad M R, Dahmardeh Ghale no F, Sabori H et al. The effect of hydroalcoholic extract of Prosopis farcta on weight, blood glucose and gene expression of Pyruvate Kinase in Diabetic Rats (Type1). Jms.2017; 4 (4) :1-9 49.Arsalandeh F, Hoseini SM, Hoseini J.Effects of Allium hirtifoliu extract on gene expression of glycogene phosphorylase and phosphoenol pyruvate carboxykinase. First National Student Conference of Biotechn.2012;46-56. (In Persian) 50.Shahsavari G, Ehsani A, Hooshmand M. Effect of essential oils of Satureia khuzestanica Jamzad on enzyme activity and gene expression of some regulatory enzymes of glucose in diabetic and normal rats. Yafte.2008; 10(4): 71-80. (In Persian) 51.Yılmaz, S.The Levels of Pyruvate Kinase Activity in Renal and Hepatic Tissues of Rats with Diabetes Induced by Streptozotocin. Turkish Journal of Veterinary and Animal Sciences.2002;26 (3):549-553. 52.Zheng S, Huang K, Tong T.Efficacy and Mechanisms of Oleuropein in Mitigating Diabetes and Diabetes Complications. J Agric Food Chem.2021; 9;69(22):6145-6155. 53.Drira R, Chen S, Sakamoto K. Oleuropein and hydroxytyrosol inhibit adipocyte differentiation in 3 T3-L1 cells. Life Sci.2011; Nov 7;89(19-20):708-16. 54.Ahmadvand H, Shahsavari G, Tavafi M, Bagheri S, Moradkhani MR, Kkorramabadi RM, Khosravi P, Jafari M, Zahabi K, Eftekhar R, Soleimaninejad M, Moghadam S. Protective effects of oleuropein against renal injury oxidative damage in alloxan-induced diabetic rats; a histological and biochemical study. J Nephropathol.2017;6(3):204-209. 55.Nekooeian AA, Khalili A, Khosravi MB. Effects of oleuropein in rats with simultaneous type 2 diabetes and renal hypertension: a study of antihypertensive mechanisms. J
Asian Nat Prod Res.2014;16(9):953-62.
