BERRY EXTRACTS IMPROVED INFLAMMATORY CYTOKINES, ANTIOXIDANT ENZYME AND SUPPRESSED THE GENE EXPRESSION ALTERATIONS IN DIABETIC RATS

  • Farouk K. El-baz Plant Biochemistry Department, National Research Centre (NRC), 33 El Bohouth st. (former El Tahrir st.), Dokki, Giza, Egypt, P.O.12622 http://orcid.org/0000-0002-4750-3559
  • Wagdy K. B. Khalil Cell Biology Department, National Research Centre (NRC), 33 El Bohouth st. (former El Tahrir st.), Dokki, Giza, Egypt, P.O.12622
  • Hanan F. Aly Therapeutic Chemistry Department, National Research Centre (NRC), 33 El Bohouth st. (former El Tahrir st.), Dokki, Giza, Egypt, P.O.12622
  • Hoda F. Booles Cell Biology Department, National Research Centre (NRC), 33 El Bohouth st. (former El Tahrir st.), Dokki, Giza, Egypt, P.O.12622

Abstract

Objective: The present work was conducted to evaluate the ameliorative effect of red berry (Morus rubra) and white berry (Morus alba) extracts in diabetic rats.

Methods: Inflammatory biomarkers; tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), transforming growth factor-β (TGF-β), paraoxanase1 (PON1), gene expression of apoptosis and inflammatory related genes were carried out.

Results: Treatment of male rats with streptozotocin (STZ) to induce diabetes increased the levels of TNF-α, IL-1β, TGF-β, the apoptosis rates and the alterations of the pro-apoptosis (eotaxin, caspase-1, and caspase-2) and inflammation; nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB1) and allograft inflammatory factor 1 (AIF-1) related genes. While marked reduction in PON1 level was detected in STZ-induced diabetic rats. However, treatment of STZ-exposed rats with red and white berry extracts exhibited noticeable ameliorations in TNF-α, IL-1β, TGF-β levels and PON1 activity as well as low apoptosis rates and decreased the alteration of the pro-apoptosis and inflammatory related genes.

Conclusion: Red and white berry extracts exhibited attenuation in antioxidant status, suppressed inflammatory cytokines, apoptosis and the alterations in the apoptosis and inflammatory related genes induced by STZ in male rats.

Keywords: Red berry, White berry, STZ, Diabetes, TNF-α, IL-1β, Apoptotic gene, NF-κB1 and AIF-1

Downloads

Download data is not yet available.

References

1. Lindarto D, Syafril S, Zein U, Saragih A. The effect of dhawalsan-1 (Curanga fel-terrae [Lour.]) extract versus metformin on the metabolic and inflammatory characteristics of patients with newly diagnosed type 2 diabetes mellitus. Asian J Pharm Clin Res 2016;9:225-8.
2. Navarro-González JF, Mora-Fernández C. The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol 2008;19:433-42.
3. Ingle PV, Patel DM. C-reactive protein in various disease condition-an overview. Asian J Pharm Clin Res 2011;4:9-13.
4. Herder C, Brunner EJ, Rathmann W. Elevated levels of the anti-inflammatory interleukin-1 receptor antagonist precede the onset of type 2 diabetes: the Whitehall II study. Diabetes Care 2009;32:421-3.
5. Durrington PN, Mackness B, Mackness MI. Paraoxonase and atherosclerosis. Arterioscler Thromb Vasc Biol 2001;21:473-80.
6. Rozenberg O, Rosenblat M, Coleman R, Shih DM, Aviram M. Paraoxonase (PON1) deficiency is associated with increased macrophage oxidative stress: Studies in PON1-knockout mice. Free Radical Biol Med 2003;34:774-84.
7. Ferretti G, Bacchetti T. Effect of dietary lipids on paraoxonase-1 activity and gene expression. Nutr Metab Cardiovasc Dis 2012;22:88-94.
8. Loued S, Isabelle M, Berrougui H, Khalil A. The anti-inflammatory effect of paraoxonase 1 against oxidized lipids depends on its association with high-density lipoproteins. Life Sci 2012;90:82-8.
9. Deakin SP, James RW. Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1. Clin Sci (Lond) 2004;107:435-47.
10. Loued S, Berrougui H, Componova P, Ikhlef S, Helal O, Khalil A. Extra-virgin olive oil consumption reduces the age-related decrease in HDL and paraoxonase 1 anti-inflammatory activities. Br J Nutr 2013;110:1272-84.
11. Krijnen PAJ, Simsek S, Niessen HWM. Apoptosis in diabetes. Apoptosis 2009;14:1387-8.
12. Gao J, Gelber-Schwalb TA, Addeo JV, Stern ME. Apoptosis in the lacrimal gland and conjunctiva of dry eye dogs. Adv Exp Med Biol 1998;438:453-60.
13. Creagh EM, Conroy H, Martin SJ. Caspase-activation pathways in apoptosis and immunity. Immunol Rev 2003;193:10-21.
14. Zhivotovsky B, Orrenius S. Caspase-2 function in response to DNA damage. Biochem Biophys Res Commun 2005;331:859-67.
15. Mariathasan S, Newton K, Monack DM, Vucic D, French DM, Lee WP, et al. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature 2004;430:213-8.
16. Doitsh G, Galloway NL, Geng X, Yang Z, Monroe KM, Zepeda O, et al. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature 2014;505:509-14.
17. Monroe KM, Yang Z, Johnson JR, Geng X, Doitsh G, Krogan NJ, et al. IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively infected with HIV. Science 2014;343:428-32.
18. Krumschnabel G, Manzl C, Villunger A. Caspase-2:killer, savior and safeguard-emerging versatile roles for an ill-defined caspase. Oncogene 2009;28:3093-6.
19. Humbles AA, Conroy DM, Marleau S, Rankin SM, Palframan RT, Proudfoot AEI, et al. Kinetics of eotaxin generation and its relationship to eosinophil accumulation in allergic airways disease: analysis in a guinea pig model in vivo. J Exp Med 1997;186:601-12.
20. Rothenberg ME, Maclean JA, Pearlman E, Luster AD, Leder P. Targeted disruption of the chemokine eotaxin partially reduces antigen-induced tissue eosinophilia. J Exp Med 1997;185:785-90.
21. Ponath PD, Qin S, Ringler DJ, Clark-Lewis I, Wang J, Kassam N, et al. Cloning of the human eosinophil chemoattractant, eotaxin: expression, receptor binding and functional properties suggest a mechanism for selective recruitment of eosinophils. J Clin Invest 1996;97:604-12.
22. Ogilvie P, Bardi G, Clark-Lewis I, Baggiolini M, Uguccioni M. Eotaxin is a natural antagonist for CCR2 and an agonist for CCR5. Blood 2001;97:1920-4.
23. Gilmore TD. Introduction to NF-kappa b: players, pathways, perspectives. Oncogene 2006;25:6680-4.
24. Brasier AR. The NF-kappa B regulatory network. Cardiovasc Toxicol 2006;6:111-30.
25. Perkins ND. Integrating cell-signalling pathways with NF-kappa B and IKK function. Nat Rev Mol Cell Biol 2007;8:49-62.
26. Gilmore TD. The Rel/NF-kappa B signal transduction pathway: an introduction. Oncogene 1999;18:6842-4.
27. Tian B, Brasier AR. Identification of a nuclear factor kappa B-dependent gene network. Recent Prog Horm Res 2003;58:95-130.
28. Albensi BC, Mattson MP. Evidence for the involvement of TNF and NF-kappa B in hippocampal synaptic plasticity. Synapse 2000;35:151-9.
29. Meffert MK, Chang JM, Wiltgen BJ, Fanselow MS, Baltimore D. NF-kappa B functions in synaptic signaling and behavior. Nat Neurosci 2003;1072-8.
30. Levenson JM, Choi S, Lee SY, Cao YA, Ahn HJ, Worley KC, et al. A bioinformatics analysis of memory consolidation reveals the involvement of the transcription factor c-rel. J Neurosci 2004;24:3933-43.
31. Freudenthal R, Locatelli F, Hermitte G, Maldonado H, Lafourcade C, Delorenzi A, et al. Kappa-B like DNA-binding activity is enhanced after spaced training that induces long-term memory in the crab chasm agnathous. Neurosci Lett 1998;242:143-6.
32. Merlo E, Freudenthal R, Romano A. The Ikappa B kinase inhibitor sulfasalazine impairs long-term memory in the crab chasm agnathous. Neuroscience 2002;112:161-72.
33. Deininger MH, Meyermann R, Schluesener HJ. The allograft inflammatory factor-1 family of proteins. FEBS Lett 2002;514:115-21.
34. Imai Y, Ohsawa K, Nakajima K, Fukuuchi Y, Kohsaka S. Microglia-specific localization of a novel calcium binding protein, Iba1. Brain Res Mol Brain Res 1998;57:1-9.
35. Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longevity 2009;2:270-8.
36. Graf BA, Milbury PE, Blumberg JB. Flavonols, flavonones, flavanones and human health: epidemiological evidence. J Med Food 2005;8:281-90.
37. Arts ICW, Hollman PCH. Polyphenols and disease risk in epidemiologic studies. Am J Clin Nutr 2005;81:317-25.
38. Kanthal LK, Dey A, Satyavathi K, Bhojaraju P. GC-MS analysis of bio-active compounds in methanolic extract of Lactuca runcinata DC. Pharmacogn Res 2014;6:58-61.
39. Ravisankar N, Sivaraj C, Seeni S, Joseph J, Raaman N. GC-MS analysis and anticancer activity of methanol extract of leaves of Hypericum hookerianum wight and ARN. Int J Pharm Pharm Sci 2014;6:515-9.
40. AOAC (Association of Analytical Communities). Official methods of analysis of the Association of Official Analytical Chemistry. 17th ed. AOAC, Gathersubrg, MD, USA; 2005. p. 18.
41. Milani E, Nikfar S, Khorasani R, Zamani MJ, Abdollahi M. Reduction of diabetes-induced oxidative stress by phosphodiesterase inhibitors in rats. Comp Biochem Physiol Part C: Toxicol Pharmacol 2005;140C:251-5.
42. Rajesh RK, Aparna HS, Manjunatha HB. Comparative analysis of silk gland proteins of both heats shocked and normal silkworm larvae of NB4D2 strain by 2-DE. Int J Appl Agric Res 2009;4:125-30.
43. Shalaby NMM, Abd-Alla HI, Aly HF, Albalawy MA, Shaker KH, Bouajila J. Preliminary in vitro and in vivo evaluation of antidiabetic activity of Ducrosia anethifolia Boiss. and its linear furanocoumarins. Biomed Res Int 2014:1-13. http://dx.doi.org/10.1155/2014/480545
44. Matsumoto M, Hara H, Chiji H, Kasai T. Gastroprotective effect of red pigments in black chokeberry fruit (Aronia melanocarpa Elliot) on acute gastric hemorrhagic lesions in rats. J Agric Food Chem 2004;21:2226-9.
45. Dachicourt N, Bailbé D, Gangnerau MN, Serradas P, Ravel D, Portha B. Effect of gliclazide treatment on insulin secretion and beta-cell mass in noninsulin dependent diabetic Goto-kaki saki rats. Eur J Pharmacol 1998;361:243-51.
46. Villalba M, Martinez-Serrano A, Borner C, Blanco P, Satrustegui J. NMDA-induced increase in [Ca2+](i) and 45 Ca2+uptake in acutely dissociated brain cells derived from adult rats. Brain Res 1992;570:347-53.
47. Deng Y, Xu ZF, Liu W, Xu B, Yang HB, Wei YG. Riluzole-triggered GSH synthesis via activation of glutamate transporters to antagonize methylmercury-induced oxidative stress in rat cerebral cortex. Oxid Med Cell Longevity 2012:1-12. Doi: 10.1155/2012/534705
48. Ahmed HH, Shousha WG, Shalby AB, El-Mezayen HA, Ismaiel NN, Mahmoud NS. Implications of sex hormone receptor gene expression in the predominance of hepatocellular carcinoma in males: the role of natural products. Asian Pac J Cancer Prev 2014;16:4949-54.
49. Center SA. Metabolic, antioxidant, nutraceutical, probiotic, and herbal therapies relating to the management of hepatobiliary disorders. Vet Clin North Am Small Anim Pract 2004;34:67-172.
50. Nakamoto N, Kanai T. Role of toll-like receptors in immune activation and tolerance in the liver. Front Immunol 2014;5:1-8.
51. Samuni Y, Goldstein S, Dean OM, Berk M. The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta 2013;1830:4117-29.
52. Bhogal RH, Curbishley SM, Weston CJ, Adams DH, Afford SC. Reactive oxygen species mediate human hepatocyte injury during hypoxia/reoxygenation. Liver Transpl 2010;16:1303-13.
53. Czaja AJ. Hepatic inflammation and progressive liver fibrosis in chronic liver disease. World J Gastroenterol 2014;20:2515-32.
54. Lee HS. The pathogenic role of TGF-β in diabetic nephropathy diabetes and metabolism. Int J Diabetes Metab 2013;S9:1-7.
55. Lee HS. Mechanisms and consequences of TGF-β overexpression by podocytes in progressive podocyte disease. Cell Tissue Res 2012;347:129-40.
56. Mackness Mi, Durrington Pn, Mackness B. The role of paraoxonase 1 activity in cardiovascular disease: potential for therapeutic intervention. Am J Cardiovasc Drugs 2004;4:211-7.
57. Karabina Sa, Lehner An, Frank E, Parthasarathy S, Santanam N. Oxidative inactivation of paraoxonase-implications in diabetes mellitus and atherosclerosis. Biochim Biophys Acta 2005;1725:213-21.
58. Flekac M, Skrha J, Zidkova K, Lacinova Z, Hilgertova J. Paraoxonase 1 gene polymorphisms and enzyme activities in diabetes mellitus. Physiol Res 2008;57:717-26.
59. Kalousova M, Zima T, Tesarv, Dusilova-Sulkova S, Skrha J. Advanced glycoxidation end products in chronic diseases-clinical chemistry and genetic background. Mutat Res 2005;579:37-46.
60. Maritim Ac, Sanders Ra, Watkins Jb. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 2003;17:24-38.
61. Saini KS, Thompson C, Winterford CM, Walker NI, Cameron DP. Streptozotocin at low doses induces apoptosis and at high doses causes necrosis in a murine pancreatic beta cell line, INS-1. Biochem Mol Biol Int 1996;39:1229-36.
62. Turk J, Corbett JA, Romanadham S, Bohrer A, McDaniel ML. Biochemical evidence for nitric oxide formation from streptozotocin in isolated pancreatic islets. Biochem Biophys Res Commun 1993;197:1458-64.
63. Eizirik DL, Strandell E, Sandler S. Culture of mouse pancreatic islets in different glucose concentrations modifies B-cell sensitivity to streptozotocin. Diabetologia 1988;31:168-74.
64. Stennicke HR, Salvesen GS. Caspases-controlling intracellular signals by protease zymogen activation. Biochim Biophys Acta 2000;1477:299-306.
65. Maedler K, Spinas GA, Lehmann R, Sergeev P, Weber M, Fontana A, et al. Glucose induces beta-cell apoptosis via upregulation of the Fas receptor in human islets. Diabetes 2001;50:1683-90.
66. Soon YY, Tan BK. Evaluation of the hypoglycemic and antioxidant activities of Morinda officinalis in streptozotocin-induced diabetic rats. Singapore Med J 2002;43:77-85.
67. Mak DH, Ip SP, Li PC, Poon MK, Ko KM. Alterations in tissue glutathione antioxidant system in streptozotocin-induced diabetic rats. Mol Cell Biochem 1996;162:153-8.
68. Williamson G, Clifford MN. Colonic metabolites of berry polyphenols: the missing link to biological activity? Br J Nutr 2010;104:S48-66.
69. Pearson JR, Gill CI, Rowland IR. Diet, fecal water, and colon cancer development of a biomarker. Nutr Rev 2009;67:509-26.
70. Sharma M, Li L, Celver J, Killian C, Kovoor A, Seeram NP. Effects of fruit ellagitannin extracts, ellagic acid, and their colonic metabolite, urolithin A, on Wnt signaling. J Agric Food Chem 2010;58:3965-9.
71. Gonzalez-Sarrias A, Larrosa M, Tomas-Barberan FA, Dolara P, Espin JC. NF-kappa B-dependent anti-inflammatory activity of urolithins, gut microbiota ellagic acid-derived metabolites, in human colonic fibroblasts. Br J Nutr 2010;104:503-12.
Statistics
372 Views | 714 Downloads
How to Cite
El-baz, F. K., W. K. B. Khalil, H. F. Aly, and H. F. Booles. “BERRY EXTRACTS IMPROVED INFLAMMATORY CYTOKINES, ANTIOXIDANT ENZYME AND SUPPRESSED THE GENE EXPRESSION ALTERATIONS IN DIABETIC RATS”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 8, no. 11, Oct. 2016, pp. 294-02, doi:10.22159/ijpps.2016v8i11.14480.
Section
Original Article(s)