DOI QR코드

DOI QR Code

Beneficial Antioxidative and Antiperoxidative Effect of Cinnamaldehyde Protect Streptozotocin-Induced Pancreatic β-Cells Damage in Wistar Rats

  • Subash-Babu, P. (Department of Food Sciences and Nutrition, College of Food Sciences and Agriculture, King Saud University) ;
  • Alshatwi, Ali A. (Department of Food Sciences and Nutrition, College of Food Sciences and Agriculture, King Saud University) ;
  • Ignacimuthu, S. (Division of Ethnopharmacology, Entomology Research Institute, Loyola College)
  • Received : 2013.11.22
  • Accepted : 2014.01.10
  • Published : 2014.01.31

Abstract

The present study was aimed to evaluate the antioxidant defense system of cinnamaldehyde in normal, diabetic rats and its possible protection of pancreatic ${\beta}$-cells against its gradual loss under diabetic conditions. In vitro free radical scavenging effect of cinnamaldehyde was determined using DPPH (1,1-diphenyl-2-dipicrylhydrazyl), superoxide radical, and nitric oxide radical. Streptozotocin (STZ) diabetic rats were orally administered with cinnamaldehyde at concentrations of 5, 10 and 20 mg/kg body weight for 45 days. At the end of the experiment, the levels of plasma lipid peroxides and antioxidants such as vitamin C, vitamin E, ceruloplasmin, catalase, superoxide dismutase, reduced glutathione and glutathione peroxidase were determined. A significant increase in the levels of plasma glucose, vitamin E, ceruloplasmin, and lipid peroxides and significant decrease in the levels of plasma insulin and reduced glutathione were observed in the diabetic rats. Also the activities of pancreatic antioxidant enzymes were altered in the STZ-induced diabetic rats. The altered enzyme activities were reverted to near-normal levels after treatment with cinnamaldehyde and glibenclamide. Histopathological studies also revealed a protective effect of cinnamaldehyde on pancreatic ${\beta}$-cells. Cinnamaldehyde enhances the antioxidant defense against reactive oxygen species produced under hyperglycemic conditions and thus protects pancreatic ${\beta}$-cells against their loss and exhibits antidiabetic properties.

Acknowledgement

Supported by : King Saud University

References

  1. Halliwell, B. and Gutteridge, J. M. (1990) The antioxidants of human extracellular fluids. Arch. Biochem. Biophys. 280, 1-8. https://doi.org/10.1016/0003-9861(90)90510-6
  2. Ialenti, S., Moncada, M. and Rosa, D. (1993) Modulation of adjuvant arthritis by endogenous nitric oxide. Brit. J. Pharmacol. 110, 701-706. https://doi.org/10.1111/j.1476-5381.1993.tb13868.x
  3. Jia, J., Zhang, X., Hu, Y. S., Wu, Y., Wang, Q. Z., Li, N. N., Guo, Q. C. and Dong, X. C. (2009) Evaluation of in vivo antioxidant activities of Ganoderma lucidum polysaccharides in STZ-diabetic rats. Food Chem. 115, 32-36. https://doi.org/10.1016/j.foodchem.2008.11.043
  4. Jiang, Z. Y., Hunt, J. V. and Wolff, S. P. (1992) Ferrous ion oxidation in the presence of Xylenol orange for detection of lipid hydroperoxide in low density lipoprotein. Anal. Biochem. 202, 384-389. https://doi.org/10.1016/0003-2697(92)90122-N
  5. Kakkar, R., Kalra, J., Mantha, S. V. and Prasad, K. (1995) Lipid peroxidation and activity of antioxidant enzymes in diabetic rats. Mol. Cell. Biochem. 151, 113-119. https://doi.org/10.1007/BF01322333
  6. Kinalski, M., Sledziewski, A., Telejko, B., Zarzycki, W. and Kinalska, I. (2000) Lipid peroxidation and scavenging enzyme activity in streptozotocin-induced diabtetes. Acta Diabetol. 37, 179-183. https://doi.org/10.1007/s005920070002
  7. Lee, H. S. (2002) Inhibitary activity of Cinnamomum cassia bark derived component against rat lens aldolase reductase. J. Pharm. Pharm. Sci. 5, 226-230.
  8. Lee, J. S., Jeon, S. M., Park, E. M., Huk, T. L., Kwon, O. S., Lee, M. K. and Cois, M. S. (2003) Cinnamate supplementation enhances hepatic lipid metabolism and antioxidant defense systems in high cholesterol-fed rats. J. Med. Food 6, 183-191. https://doi.org/10.1089/10966200360716599
  9. Miller, N. J. and Rice-Evans, C. (1997) Factors influencing the antioxidant activity determined by the $ABTS^{.s}$ radical cation assay. Free Radic. Res. 26, 195-199. https://doi.org/10.3109/10715769709097799
  10. Lowry, O. H., Rosenbrough, N. J., Farr, A. L. and Randall, R. (1951) Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265-275.
  11. Maritim, A. C., Sanders, R. A. and Watkins, J. B. (2003) Effects of alpha-lipoic acid on biomarkers of oxidative stress in streptozotocin-induced diabetic rats. J. Nutr. Biochem. 14, 288-94. https://doi.org/10.1016/S0955-2863(03)00036-6
  12. Ellman, G. C. (1959) Tissue Sulfhydryl groups. Arch. Biochem. Biophys. 82, 70-77. https://doi.org/10.1016/0003-9861(59)90090-6
  13. Green, L. C., Wanger, D. A., Glogowski, J., Skipper, P. L., Wishnok, J. S. and Tannenbaum, S. R. (1982) Analysis of nitrate and [$^{15}N$] nitrate in biological fluids. Anal. Biochem. 126, 131-138. https://doi.org/10.1016/0003-2697(82)90118-X
  14. Desai, I. D. (1984) Vitamin E analysis methods for animal tissues. Methods Enzymol. 105, 138-147. https://doi.org/10.1016/S0076-6879(84)05019-9
  15. Bagri, P., Ali, M., Aeri, V., Bhowmik, M. and Sultana, S. (2009) Antidiabetic effect of Punica granatum flowers: effect on hyperlipidemia, pancreatic cells lipid peroxidation and antioxidant enzymes in experimental diabetes. Food Chem. Toxicol. 47, 50-54. https://doi.org/10.1016/j.fct.2008.09.058
  16. Bhatia, A. L. and Jain, M. (2003) Amaranthus paniculatus (Linn.) improves learning after radiation stress. J. Ethnopharmacol. 85, 73-79. https://doi.org/10.1016/S0378-8741(02)00337-9
  17. Bhattacharya, S. K., Satyan, K. S. and Chakrabarti, A. (1997) Effect of trasina, an ayurvedic herbal formulation on pancreatic islet superoxide dismutase activity in hyperglycaemic rats. Indian J. Exp. Biol. 35, 297-299.
  18. Blois, M. S. (1958) Antioxidant determinations by the use of stable free radical. Nature 181, 1199-1200. https://doi.org/10.1038/1811199a0
  19. Cao, G., Sofic, E. and Prior, R. L. (1997) Antioxidant and prooxidant behaviour of flavonoides: structure-activity relationships. Free Radic. Bio. Med. 22, 749-760. https://doi.org/10.1016/S0891-5849(96)00351-6
  20. Dormandy, T. L. (1980) Free radical reactions in biological systems. Ann. R. Coll. Surg. Engl. 62, 188-194.
  21. Duncan, B. D. (1957) Multiple range tests for correlated and heteroscedastic means. Biometrics 13, 164-176. https://doi.org/10.2307/2527799
  22. Misra, H.P. and Fridovich, I. (1972) The role of superoxide anion in the auto oxidation of epinephrine and a simple assay of superoxide dismutase. J. Biol. Chem. 247, 3170-3175.
  23. Moser, U. and Bendich, A. (1991) Vitamin C. In Handbook of vitamins, 2nd Ed, (Machlin, L. J., Ed), pp195-232. Marcel Dekker, New York.
  24. Mullarkey, C. J., Edelstein, D. and Brownlee, L. (1990) Free radical generation by early glycation products: a mechanism for accelerated atherogenesis in diabetes. Biochem. Biophys. Res. Commun. 173, 932-939. https://doi.org/10.1016/S0006-291X(05)80875-7
  25. Nishimiki, M., Rao, N. A. and Yagi, K. (1972) The occurance of superoxide anion in the reaction of reduced phenazine methosulphate and molecular oxygen. Biochem. Biophys. Res. Commun. 46, 849-854. https://doi.org/10.1016/S0006-291X(72)80218-3
  26. Nogueira, F. N., Carvalho, A. M., Yamaguti, P. M. and Nicolau, J. (2005) Antioxidants parameters and lipid peroxidation in salivary glands of streptozotocin-induced diabetic rats. Clin. Chim. Acta 353, 133-139. https://doi.org/10.1016/j.cccn.2004.11.004
  27. Qujeq, D. and Rezvani, T. (2007) Catalase (antioxidant enzyme) activity in streptozotocin- induced diabetic rats. Int. J. Diabetes Metab. 15, 22-24.
  28. Omaye, S. T., Turnabull, J. C. and Sanberlick, H. E. (1979) Selected methods for the determination of ascorbic acid in animal cells, tissues and fluids. Methods Enzymol. 62, 3-11. https://doi.org/10.1016/0076-6879(79)62181-X
  29. Pitozzi, V., Giovannelli, L., Bardini, G., Rotella, C. M. and Dolara, P. (2003) Oxidative DNA damage in peripheral blood cells in type 2 diabetes mellitus: higher vulnerability of polymorphonuclear leukocytes. Mutat. Res. 529, 129-133. https://doi.org/10.1016/S0027-5107(03)00114-3
  30. Qin, B., Nagasaki, M., Ren, M., Bajotto, G., Oshida, Y. and Sato, Y. (2003) Cinnamon extract (traditional herb) potentiates in vivo insulin regulated glucose utilization via enhancing insulin signaling in rats. Diabetes Res. Clin. Pract. 62, 139-148. https://doi.org/10.1016/S0168-8227(03)00173-6
  31. Rajarajeswari, N. and Pari, L. (2011) Antioxidant role of coumarin on streptozotocin-nicotinamide-induced type 2 diabetic rats. J. Biochem. Mol. Toxicol. 25, 355-361. https://doi.org/10.1002/jbt.20395
  32. Ravi, K., Ramachandran, B. and Subramaniyan, S. (2004) Effect of Eugenia jambolana seed kernel on antioxidant defense system in streptozotocin-induced diabetes in rats. Life Sci. 75, 2717-2731. https://doi.org/10.1016/j.lfs.2004.08.005
  33. Ravin, H. A. (1961) An improved colorimetric enzymatic assay of ceruloplasmin. J. Lab. Clin. Med. 58, 161-168.
  34. Ray, G. and Husain, S. A. (2002) Oxidants, antioxidants and carcinogenesis. Indian J. Exp. Biol. 40, 1213-1232.
  35. Rolo, A. P. and Palmeira, C. M. (2006) Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress. Toxicol. Appl. Pharmacol. 212, 167-178. https://doi.org/10.1016/j.taap.2006.01.003
  36. Sharma, S. B., Nasir, A., Prabhu, K. M., Murthy, P. S. and Dev, G. (2003) Hypoglycemic and hypolipidemic effect of ethanolic extract of seeds of Eugenia jambolana in alloxan induced diabetic rabbits. J. Ethnopharmacol. 85, 201-206. https://doi.org/10.1016/S0378-8741(02)00366-5
  37. Rotruck, J. T., Pope, A. L., Ganther, H. E., Swanson, A. B., Hafeman, D. G. and Hoekstra, W. G. (1973) Selenium; Biochemical role as a component of glutathione peroxidase. Science 179, 588-590. https://doi.org/10.1126/science.179.4073.588
  38. Sanchez-Moreno, C., Larrauri, J. A. and Saura-Calixto, F. (1999) Free radical scavenging capacity and inhibition of lipid peroxidation of wines, grape juices and related polyphenolic constituents. Food Res. Int. 32, 407-412. https://doi.org/10.1016/S0963-9969(99)00097-6
  39. Saxena, A. K., Srivastava, P., Kale, R. K. and Baquer, N. Z. (1993) Impaired antioxidant status in diabetic rat liver: effect of vanadate. Biochem. Pharmacol. 45, 539-542.
  40. Simmons, R. A. (2006) Developmental origins of diabetes: the role of oxidative stress. Free Radic. Biol. Med. 40, 917-922. https://doi.org/10.1016/j.freeradbiomed.2005.12.018
  41. Soto, C., Recoba, R., Barron, H., Alvarez, C. and Favari, L. (2003) Silymarin increases antioxidant enzymes in alloxan induced diabetes in rat pancreas. Comp. Biochem. Physiol. C. Toxicol. Pharmacol. 136, 205-212. https://doi.org/10.1016/S1532-0456(03)00214-X
  42. Stocker, R. and Frei, B. (1991) Endogenous antioxidant defense in human blood plasma. In Oxidative Stress: Oxidants and antioxidants (H. Sies, Ed), pp213-243. Academic Press, London.
  43. Subash Babu, P. and Prince, P. S. M. (2004) Antihyperglycemic and antioxidant effect of Hyponidd, an ayurvedic herbomineral formulation in streptozotocin induced diabetic rats. J. Pharm. Pharmacol. 56, 1435-1442. https://doi.org/10.1211/0022357044607
  44. Subash-Babu, P., Prabuseenivasan, S. and Ignacimuthu, S. (2007) Cinnamaldehyde- A potential antidiabetic agent. Phytomedicine 14, 15-22.
  45. World Health Organization. (2008) Prevalence data of diabetes worldwide. Available at http://www.who.int/ media centre/fact sheets/fs312/en/index.html, Accessed 24.04.2008.
  46. Subash-Babu, P., Ignacimuthu, S., Agastian, P. and Varghese, B. (2009) Partial regeneration of beta-cells in the islets of Langerhans by Nymphayol a sterol isolated from Nymphaea stellata (Willd.) flowers. Bioorg. Med. Chem. 17, 2864-2870. https://doi.org/10.1016/j.bmc.2009.02.021
  47. Takahara, S., Hamilton, B. H., Nell, J. V., Kobara, T. Y., Ogura, Y. and Nishimura, E. T. (1960) Hypocatalasemia, a new genetic carrier state. J. Clin. Inv. 39, 610-619. https://doi.org/10.1172/JCI104075
  48. Wefers, H. and Sies, H. (1988) The protection by ascorbate and glutathione against microsomal lipid peroxidation is dependent on vitamin E. Eur. J. Biochem. 174, 353-357. https://doi.org/10.1111/j.1432-1033.1988.tb14105.x
  49. Yagi, K. (1976) A simple fluorometric assay for lipid peroxide in blood plasma. Biochem. Med. 15, 212-216. https://doi.org/10.1016/0006-2944(76)90049-1
  50. Yokozawa, T., Chen, C. P., Dong, E., Tanaka, T., Nonaka, G. I. and Nishioka, I. (1998) Study on the inhibitory effect of tannins and flavonoids against the 1,1-diphenyl-2-picrylhydrazyl radical. Biochem. Pharmacol. 56, 213-222. https://doi.org/10.1016/S0006-2952(98)00128-2

Cited by

  1. Cinnamaldehyde in diabetes: A review of pharmacology, pharmacokinetics and safety vol.122, 2017, https://doi.org/10.1016/j.phrs.2017.05.019
  2. Vitis vinifera(Muscat Variety) Seed Ethanolic Extract Preserves Activity Levels of Enzymes and Histology of the Liver in Adult Male Rats with Diabetes vol.2015, 2015, https://doi.org/10.1155/2015/542026
  3. Cinnamaldehyde Mitigates Carbon Tetrachloride-induced Acute Liver Injury in Rats Through Inhibition of Toll-like Receptor 4 Signaling Pathway vol.12, pp.8, 2016, https://doi.org/10.3923/ijp.2016.851.862
  4. Effect of paricalcitol on pancreatic oxidative stress, inflammatory markers, and glycemic status in diabetic rats 2017, https://doi.org/10.1007/s11845-017-1635-7
  5. Maternal cinnamon extract intake during lactation leads to sex-specific endocrine modifications in rat offspring vol.97, pp.11, 2017, https://doi.org/10.1002/jsfa.8253
  6. Cinnamaldehyde potentially attenuates gestational hyperglycemia in rats through modulation of PPARγ, proinflammatory cytokines and oxidative stress vol.88, 2017, https://doi.org/10.1016/j.biopha.2017.01.054
  7. Comparative study of herbal plants on the phenolic and flavonoid content, antioxidant activities and toxicity on cells and zebrafish embryo 2017, https://doi.org/10.1016/j.jtcme.2016.12.006
  8. Evaluating Pharmacological Effects of Two Major Components of Shuangdan Oral Liquid: Role of Danshensu and Paeonol in Diabetic Nephropathy Rat vol.24, pp.5, 2016, https://doi.org/10.4062/biomolther.2015.191
  9. Antioxidative and Anti-Inflammatory Activities of Galloyl Derivatives and Antidiabetic Activities of Acer ginnala vol.2017, 2017, https://doi.org/10.1155/2017/6945912
  10. Changes in pancreatic histology, insulin secretion and oxidative status in diabetic rats following treatment with Ficus deltoidea and vitexin vol.17, pp.1, 2017, https://doi.org/10.1186/s12906-017-1762-8
  11. In vitro antioxidant activities of resveratrol, cinnamaldehyde and their synergistic effect against cyadox-induced cytotoxicity in rabbit erythrocytes vol.40, pp.2, 2017, https://doi.org/10.1080/01480545.2016.1193866
  12. Cinnamaldehyde Ameliorates Cadmium-Inhibited Root Elongation in Tobacco Seedlings via Decreasing Endogenous Hydrogen Sulfide Production vol.22, pp.1, 2016, https://doi.org/10.3390/molecules22010015
  13. Cinnamaldehyde and Nitric Oxide Attenuate Advanced Glycation End Products-Induced the JAK/STAT Signaling in Human Renal Tubular Cells vol.116, pp.6, 2015, https://doi.org/10.1002/jcb.25058
  14. Anti-oxidative and anti-inflammatory effects of cinnamaldehyde on protecting high glucose-induced damage in cultured dorsal root ganglion neurons of rats vol.22, pp.1, 2016, https://doi.org/10.1007/s11655-015-2103-8
  15. Effect of Resveratrol, Cinnamaldehyde and their Combinations on the Antioxidant Defense System and ATP Release of Rabbit Erythrocytes: In vitro Study vol.12, pp.1, 2017, https://doi.org/10.3923/ajava.2017.1.9
  16. Study of the Hypoglycemic Activity of Derivatives of Isoflavones from Cicer arietinum L. vol.2017, 2017, https://doi.org/10.1155/2017/8746823
  17. Cinnamaldehyde ameliorates STZ-induced rat diabetes through modulation of IRS1/PI3K/AKT2 pathway and AGEs/RAGE interaction pp.1432-1912, 2018, https://doi.org/10.1007/s00210-018-1583-4
  18. -induced skeletal muscle atrophy by ameliorating the proteolytic and antioxidant defense systems pp.00219541, 2018, https://doi.org/10.1002/jcp.27348
  19. Cinnamaldehyde exerts vasculoprotective effects in hypercholestrolemic rabbits vol.391, pp.11, 2018, https://doi.org/10.1007/s00210-018-1547-8
  20. Spice-Derived Bioactive Ingredients: Potential Agents or Food Adjuvant in the Management of Diabetes Mellitus vol.9, pp.1663-9812, 2018, https://doi.org/10.3389/fphar.2018.00893
  21. Jiao-Tai-Wan Improves Cognitive Dysfunctions through Cholinergic Pathway in Scopolamine-Treated Mice vol.2018, pp.2314-6141, 2018, https://doi.org/10.1155/2018/3538763
  22. The effects of cinnamaldehyde on acute or chronic stress-induced anxiety-related behavior and locomotion in male mice pp.1607-8888, 2019, https://doi.org/10.1080/10253890.2019.1567710