Volume 26, Issue 5 (8-2019)
RJMS 2019, 26(5): 67-78 |
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nikkhah S, sazgar H, Zia-jahromi N. Effect of silymarin on blood glucose concentration and pax4 gene expression and histopathology of pancreatic tissue in streptozotocin-induced diabetic wistar rats. RJMS 2019; 26 (5) :67-78
URL: http://rjms.iums.ac.ir/article-1-5546-en.html
URL: http://rjms.iums.ac.ir/article-1-5546-en.html
Islamic Azad University, Shahrekord, Iran , h.seazgar@iaushk.com
Abstract: (3533 Views)
Background: Considering the high rates of diabetes in Iran and the world and also due to the lower side effects of medicinal plants compared to industrial and chemical arbitrators, this study examined the effect of the active ingredient of tall moss (silymarin) on the expression of pax4 gene, one of the key genes for development and reconstruction of pancreatic beta cells.
Methods: The present study was of a fundamental type and its experimental method. 42 male Wistar rats were randomly selected and divided into 7 groups of sixths. Diabetic rats with diabetes mellitus straptozotocin have been diagnosed with fasting blood glucose every 10 days and then anesthetized and described after the end of the rats with anesthetics. A portion of the pancreatic tissue was isolated and the pax4 gene expression was analyzed using Real Time RT PCR.
Results: The active ingredient of silymarin caused a significant decrease in blood glucose levels in all of the patient groups receiving the drug (C, D, E, F). This drug significantly increased the expression of pax4 gene in the doses of mg/kg 150 and 100 silymarin (D, E) compared to diabetic controls (B) and other groups receiving silymarin and metformin (p<0.05). This increase in the gene expression is not dose-dependent and in the group treated by 150 mg/kg (D) dose of silymarin, the gene expression is lower than the group treated by 100 mg/kg (D) dose of silymarin.
Conclusion: The active ingredient of silymarin significantly increased the expression of the pax4 gene, and this gene, one of the beta cells repair and upkeep genes, improves and restores beta cells and pancreatic islets.
Methods: The present study was of a fundamental type and its experimental method. 42 male Wistar rats were randomly selected and divided into 7 groups of sixths. Diabetic rats with diabetes mellitus straptozotocin have been diagnosed with fasting blood glucose every 10 days and then anesthetized and described after the end of the rats with anesthetics. A portion of the pancreatic tissue was isolated and the pax4 gene expression was analyzed using Real Time RT PCR.
Results: The active ingredient of silymarin caused a significant decrease in blood glucose levels in all of the patient groups receiving the drug (C, D, E, F). This drug significantly increased the expression of pax4 gene in the doses of mg/kg 150 and 100 silymarin (D, E) compared to diabetic controls (B) and other groups receiving silymarin and metformin (p<0.05). This increase in the gene expression is not dose-dependent and in the group treated by 150 mg/kg (D) dose of silymarin, the gene expression is lower than the group treated by 100 mg/kg (D) dose of silymarin.
Conclusion: The active ingredient of silymarin significantly increased the expression of the pax4 gene, and this gene, one of the beta cells repair and upkeep genes, improves and restores beta cells and pancreatic islets.
References
1. 1. Meusel LA, Kansal N, Tchistiakova E, Yuen W, MacIntosh BJ, Greenwood CE, Anderson ND. A systematic review of type 2 diabetes mellitus and hypertension in imaging studies of cognitive aging: time to establish new norms. Front Aging Neurosci. 2014;8(6):148. doi: https://doi.org/10.3389/fnagi.2014.00148
2. 2. Patel DK, Kumar R, Prasad SK, Sairam K, Hemalatha S. Antidiabetic and in vitro antioxidant potential of Hybanthus enneaspermus (Linn) F. Muell in streptozotocin-induced diabetic rats. Asian Pac J Trop Biomed. 2011;1(4):316-322. doi: 10.1016/S2221-1691(11)60051-8
3. 3.Das-Munshi J, Stewart R, Ismail K, Bebbington PE, Jenkins R, Prince MJ. Diabetes, Common Mental Disorders and disability: Findings From the UK National Psychiatric Morbidity Survey. Psychosomatic Medicine. 2007;69(6):543-550. doi: 10.1016/S2221-1691(11)60051-8
4. 4. Wilkin TJ. The accelerator hypothesis: weight gain as the missing link between type I and type II diabetes. Diabetologia. 2001;44(7):914-922. doi: 10.1007/s001250100548
5. 5. Grant SF, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, Sainz J, Helgason A, Stefansson H, Emilsson V, Helgadottir A. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. 2006;38(3):320-323. DOI: 10.1038/ng1732
6. 6. Kondrashova A, Reunanen A, Romanov A, Karvonen A, Viskari H, Vesikari T, Ilonen J, Knip M, Hyöty H. A sixfold gradient in the incidence of type 1 diabetes at the eastern border of Finland. Ann Med. 2005;37(1):67-72. https://doi.org/10.1080/07853890410018952
7. 7. Guyton A, Hall JE. Insulin, Glucagon and diabetes medical Physiology. Translation Sepehri H, Rastgar Farajzadeh A, ghassemi K. 4th ed Tehran Andishhe Rafie perssm. 2011:1194-1215.
8. 8. Pinent M, Castell A, Baiges I, Montagut G, Arola L, Ardevol A. Bioactivity of flavonoids on insulin-secreting cells. Compr Rev Food Sci F.2008;7:299-308. https://doi.org/10.1111/j.1541-4337.2008.00048.x
9. 9. Chakrabarti SK, Mirmira RG. Transcription factors direct the development and function of pancreatic β cells. TRENDS in Endocrinology and Metabolism. 2003;14(2):78-84. DOI: doi.org/10.1016/S1043-2760(02)00039-5
10. 10. Sasai Y, Kageyama R, Tagawa Y, Shigemoto R, Nakanishi S. Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split. Genes Develop. 1992;6(12):2620-2634. doi: 10.1101/gad.6.12b.2620
11. 11. Tamura T, Izumikawa Y, Kishino T, Soejima H, Jinno Y, Niikawa N. Assignment of the human Pax4 gene to chromosome band 7q32 by fluorescence in situ hybridization. Cytogenet, Cell Genet. 1994;66(2):132-134. Doi: https://doi.org/10.1159/000133684
12. 12. Sosa-Pineda B, Chowdhury K, Torres M, Oliver G, Gruss P. The Pax4 gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreas. Nature. 1997;386(6623):399-402. doi: 10.1038/386399a0
13. 13. Blyszczuk P, Czyz J, Kania G, Wagner M, Roll U, Onge L, Wobus A. Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells. Pnas. 2003;100(3):998-1003. Doi: 10.1073/pnas.0237371100
14. 14. Mellado-Gil JM, Jimenez-Moreno C, Martin-Montalvo A, Alvarez-Mercado AI, Fuente-Martin E, Cobo-Vuilleumier N, Lorenzo PI, et al. Pax4 preserves endoplasmic reticulum integrity preventing beta cell degeneration in a mouse model of type 1 diabetes mellitus. Diabetologia. 2016;59(4):755-765. doi: 10.1007/s00125-016-3864-0
15. 15. Tokuyama Y, Yagui K, Sakurai K, Hashimoto N, Saito Y, Kanatsuka A. Molecular cloning of rat Pax4: identification of four isoforms in rat insulinoma cells. Biochemical and Biophysical Research Communications. 1998;248(1):153-156. doi.org/10.1006/bbrc.1998.8925
16. Fallah Huseini H, Fakhrzadeh H, Larijani B, Shikh Samani A. Review of anti-diabetic medicinal plant used in traditional medicine. JMP. 2006;1(S2):1-8. URL: http://jmp.ir/article-1-583-fa.html
17. 20. Abenavoli L, Capasso R, Milic N, Capasso F. milk thistle in liver diseases: past, present, future. phytother res. 2010;24(10):1423-1432. Doi: 10.1002/ptr.3207
18. 21. Fallah Huseini H, Yazdani D, Amin G, Makkizadeh M. Milk thistle and cancer. JMP. 2005;1(S1):46-53
19. URL: http://jmp.ir/article-1-832-fa.html
20. 22. Campos R, Garrido A, Guerra R, Valenzuela A. Silybin dihemsuccinate protects against glutathioine depletion and lipid peroxidation induced by acetaminophen on rat liver. Plant Meidca. 1998;55(5):417-419. Doi: 10.1055/s-2006-962055
21. 23. Sakai I, Izumi SI, Murano T, Okuwaki S, Makino T, Suzuki T. Presence of aldose reductase inhibitors in tea leaves. Jpn J Pharmacol. 2001;85(3):322-326. Doi: https://doi.org/10.1254/jjp.85.322
22. 24. Velussi M, Cernigoi AM, De Monte A, Dapas F, Caffau C, Zilli M. Long- term (23 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. J Hepatol. 1997;26(4):871-879. Doi: https://doi.org/10.1016/S0168-8278(97)80255-3
23. 25. Dixit N, Baboota S, Kohli K, Ahmad S, Ali J. Silymarin: A review of Pharmacological aspects and bioavailability enhancement approaches. Indian J Pharamacol. 2007;39(4):172-179. Doi: 10.4103/0253-7613.36534
24. 26. Soto C, Raya L, Pereza J, Gonzalez I, Perez S. Silymarin Induces Expression of Pancreatic Nkx6.1 Transcription Factor and β-Cells Neogenesis in a Pancreatectomy Mode. Molecules. 2014;19(4):4654-4668. Doi: https://doi.org/10.3390/molecules19044654
25. 27. Kvasnicka F, Biba B, Sevcik R, Voldrich M, Kratka J. Analysis of the active components of Silymarin. Journal of Chromatography. 2003;990(1-2):239-245. Doi: https://doi.org/10.1016/S0021-9673(02)01971-4
26. 28.Musavi Ezmar SF, Moazeni M, Heidarian A, Alipanahmoghadam R, Rafieian M, Ebrahimi M. The effect of the extract Chevilan (Ferulago angulate) on glucose and lipid in diabetic rats. Journal of Endocrinology and Metabolism tiny Druze chiefs Iran. 2015;3:237-230. URL: http://ijem.sbmu.ac.ir/article-1-1871-fa.html
27. 29. Hedayati M, Pouraboli I, Pouraboli B. Effect of Methanolic Extract of Otostegia persica on Serum Levels of Glucose and Lipids in Type I Diabetic Male Rats. Iranian Journal of Endocrinology and Metabolism. 2010; 12 (4):435-442. URL: http://ijem.sbmu.ac.ir/article-1-936-fa.html
29. 31. Valenzuela A, Garrido A. Biochemical bases of the pharmacological action of the flavonoid silymarin and of its structural isomer silibinin. Biol Res. 1994;27(2):105–112. PMID:8640239
30. 32. Soto CP, Perez BL, Favari LP, Reyes JL. Prevention of alloxan-induced diabetes mellitus in the rat by silymarin. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1998;119(2):125–129. https://doi.org/10.1016/S0742-8413(97)00198-9
31. 33. Stockinger l, Trost w, Uebel h. Quantification électronique des lesions hépatiques experimentales, mises en evidence en histologic. Arch Anat Cytol Pathol. 1976;24: 203-209. Google Scholar
32. 34. Soto C, Recoba R, Barro´n H, Alvarez C, Favari L. Silymarin increases antioxidant enzymes in alloxan-induced diabetes mellitus in the rat pancreas. Comparative Biochemistry and Physiology. 2003;136(3):205–212. https://doi.org/10.1016/S1532-0456(03)00214-X
33. 35. Hunt J, Dean R, Wolff SP. Hydroxyl radical production and autoxidative glycosylation glucose autoxidation as the cause of oxidative damage in the experimental glycation model of diabetes mellitus and ageing. Biochemical Journal. 1998;256(1):205–212. DOI: 10.1042/bj2560205
34. 36. Gokkusu C, Palanduz S, Ademoglu E, Tamer S. Oxidant and antioxidant systems in niddm patients: influence of vitamin E supplementation. Endocrinology Research. 2001;27(3):377–386. https://doi.org/10.1081/ERC-100106015
35. 37. Som S, Basu S, Mukherjee D, Deb S, Choudhury PR, Mukherjee S, Chatterjee SN, Chatterjee IB. Ascorbic acid metabolism in diabetes mellitus. Metabolism. 1981;30(6):572-577. https://doi.org/10.1016/0026-0495(81)90133-5
36. 38. valenzuela A, Aspillaga, Vial S, Guerra R. Selectivity of silymarin in the increase of the glutathione content in different tissues of the rat. Planta Medica. 1989;55(5):420–422 DOI:10.1055/s-2006-962056
37. 39. Utrilla M. Natural products with hepatoprotective action. Methods Find Experimental Clinical Pharmacology 18 (Suppl. B).1996:11–12. PMID: 8899686
38. 40. Blyszczuk P, Czyz J, Kania G, Wagner M, Roll U, St-Onge L, Wobus AM. Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells. Proc Natl Acad Sci U S A. 2003;100(3):998-1003. DOI: 10.1073/pnas.023737110
39. 41. Collombat P, Xu X, Ravassard P, Sosa-Pineda B, Dussaud S, Billestrup N, et al. The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into α and subsequently β cells. Cell. 2009;138(3):449-462. DOI: 10.1016/j.cell.2009.05.035
40. 42. Soto C, Raya L, Juárez J, Pérez J, González I. Effect of Silymarin in Pdx-1 expression and the proliferation of pancreatic β-cells in a pancreatectomy model. Phytomedicine. 2014;21(3):233-239. DOI: 10.1016/j.phymed.2013.09.008
41. 43. Soto C, Raya L, Pérez J, González I, Pérez S. Silymarin induces expression of pancreatic Nkx6. 1 transcription factor and β-cells neogenesis in a pancreatectomy model. Molecules. 2014;19(4):4654-68. DOI: 10.3390/molecules19044654
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