Accessible Requires Authentication Published by De Gruyter May 8, 2015

Syzygium cumini seed extract ameliorates adenosine deaminase activity and biochemical parameters but does not alter insulin sensitivity and pancreas architecture in a short-term model of diabetes

Paula Eliete Rodrigues Bitencourt, Karine Santos De Bona, Lariane Oliveira Cargnelutti, Gabriela Bonfanti, Aline Pigatto, Aline Boligon, Margareth L. Athayde, Felipe Pierezan, Régis Adriel Zanette and Maria Beatriz Moretto

Abstract

Background: The effects of the aqueous seed extract of Syzygium cumini (ASc) in a short-term model of diabetes in rats are little explored. The present study was designed to evaluate the effect of the ASc on adenosine deaminase (ADA) activity and on biochemical and histopathological parameters in diabetic rats.

Methods: ASc (100 mg/kg) was administered for 21 days in control and streptozotocin (STZ)-induced (60 mg/kg) diabetic rats. ADA activity, lipoperoxidation (cerebral cortex, kidney, liver and pancreas) and biochemical (serum) and histopathological (pancreas) parameters were evaluated.

Results: The main findings in this short-term model of Diabetes mellitus (DM) were that the ASc (i) significantly reverted the increase of ADA activity in serum and kidney; (ii) ameliorated the lipoperoxidation in the cerebral cortex and pancreas of the diabetic group; (iii) demonstrated hypolipidemic and hypoglycemic properties and recovered the liver glycogen; and iv) prevented the HOMA-IR index increase in the diabetic group. Therefore, the ASc can be a positive factor for increasing the availability of substrates with significant protective actions, such as adenosine. Moreover, by maintaining glycogen and HOMA-IR levels, the extract could modulate the hyperglycemic state through the direct peripheral glucose uptake.

Conclusions: Our data revealed that the short-term treatment with ASc has an important protective role under pathophysiological conditions caused by the early stage of DM. These results enhance our understanding of the effect of the ASc on the purinergic system in DM.

Acknowledgments

The authors wish to thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS). The first author acknowledges the fellowship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. American Diabetes Association. ADA standards of medical care in diabetes 2013. Diabetes Care2013;36:S11S66. Search in Google Scholar

2. Sociedade Brasileira de Diabetes. SBD Diretrizes da Sociedade Brasileira de Diabetes. Available at http://diabetes.org.com.br. Accessed:29Dec2014. Search in Google Scholar

3. RutkiewiczJ, GórskiJ. On the role of insulin in regulation of adenosine deaminase activity in rat tissues. FEBS Lett1990;271:7980. Search in Google Scholar

4. De BonaKS, BonfantiG, BitencourtPE, CargneluttiLO, Da SilvaTP, ZanetteRA, et al. Syzygium cumini is more effective in preventing the increase of erythrocytic ADA activity than phenolic compounds under hyperglycemic conditions in vitro. J Physiol Biochem2014;70:32130. Search in Google Scholar

5. DesrosiersMD, CembrolaKM, FakirMJ, StephensLA, JamaFM, ShameliA, et al. Adenosine deamination sustains dendritic cell activation in inflammation. J Immunol1892;2007:1884–. Search in Google Scholar

6. HoshinoT, YamadaK, MasuokaK, TsuboiI, ItohK, NonakaK, et al. Elevated adenosine deaminase activity in the serum of patients with diabetes mellitus. Diabetes Res Clin Pract1994;25:97102. Search in Google Scholar

7. BoppA, De BonaKS, BelléLP, MorescoRN, MorettoMB. Syzygium cumini inhibits adenosine deaminase activity and reduces glucose levels in hyperglycemic patients. Fund Clin Pharmacol2009;23:5017. Search in Google Scholar

8. SrivastavaS, ChandraD. Pharmacological potentials of Syzygium cumini: a review. J Sci Food Agric2013;93:208493. Search in Google Scholar

9. HelmstadterA. Syzygium cumini (L.) skeels (Myrtaceae) against diabetes–125 years of research. Pharmazie2008;63:91101. Search in Google Scholar

10. De BonaKS, BelléLP, SariMH, ThoméG, SchetingerMR, MorschVM, et al. Syzygium cumini extract decrease adenosine deaminase, 5′nucleotidase activities and oxidative damage in platelets of diabetic patients. Cell Physiol Biochem2010;26:72938. Search in Google Scholar

11. BelléLP, BitencourtPE, De BonaKS, ZanetteRA, MorescoRN, MorettoMB. Expression of CD26 and its association with dipeptidyl peptidase IV activity in lymphocytes of type 2 diabetes patients. Cell Biochem Biophys2011;61:297302. Search in Google Scholar

12. De BonaKS, BitencourtPE, BelléLP, BonfantiG, CargneluttiLO, PimentelVC, et al. Erythrocytic enzymes and antioxidant status in patients with type 2 diabetes: benefic effect of Syzygium cumini leaf extract in vitro. Diabetes Res Clin Pract2011;94:8490. Search in Google Scholar

13. BelléLP, BitencourtPE, De BonaKS, MorescoRN, MorettoMB. Association between HbA1c and dipeptidyl peptidase IV activity in type 2 diabetes mellitus. Clin Chim Acta2012;413:10201. Search in Google Scholar

14. PrincePS, MenonVP, PariL. Hypoglycemic activity of Syzygium cumini seeds: effect on lipid peroxidation in alloxan diabetic rats. J Ethnopharmacol1998;61:17. Search in Google Scholar

15. ShivannaN, NaikaM, KhanumF, KaulVK. Antioxidant, anti-diabetic and renal protective properties of Stevia rebaudiana. J Diabetes Complicat2013;27:10313. Search in Google Scholar

16. RaviK, RamachandranB, SubramanianS. Effect of Eugenia jambolana seed kernel on antioxidant defense system in streptozotocin induced diabetes in rats. Life Sci2004;75:271731. Search in Google Scholar

17. KrismanCR. A method for the colorimetric estimation of glycogen with iodine. Anal Biochem1962;4:1723. Search in Google Scholar

18. MatthewsDR, HoskerJP, RudenskiAS, NaylorBA, TreacherDF, TurnerRC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia1985;28:41219. Search in Google Scholar

19. GiustiG. Colorimetric method. In: BergmeyerHU, editor. Methods of enzymatic analysis. Weinheim: Verlag Chemie, 1984:31523. Search in Google Scholar

20. LowryOH, RosebroughNJ, FarrAL, RandallRJ. Protein measurement with the folin phenol reagent. J Biol Chem1951;193:26575. Search in Google Scholar

21. BuegeJA, AustSD. Microsomal lipid peroxidation. Methods Enzymol1978;52:30210. Search in Google Scholar

22. AnfossiG, RussoI, MassuccoP, MattielloL, CavalotF, BalboA, et al. Adenosine increases human platelet levels of cGMP through nitric oxide: possible role in its antiaggregating effect. Thromb Res2002;105:718. Search in Google Scholar

23. MelzigMF. Inhibition of adenosine deaminase activity of aortic endothelial cells by selected flavonoids. Planta Med1996;62:202. Search in Google Scholar

24. SchmatzR, MannTR, SpanevelloR, MachadoMM, ZaniniD, PimentelVC, et al. Moderate red wine and grape juice consumption modulates the hydrolysis of the adenine nucleotides and decreases platelet aggregation in streptozotocin-induced diabetic rats. Cell Biochem Biophys2013;65:12943. Search in Google Scholar

25. VallonV, MuhlbauerB, OsswaldH. Adenosine and kidney function. Physiol Rev2006;86:90140. Search in Google Scholar

26. PawelczykT, SakowiczM, Szczepanska-KonkelM, AngielskiS. Decreased expression of adenosine kinase in streptozotocin-induced diabetes mellitus rats. Arch Biochem Bioph2000;375:16. Search in Google Scholar

27. AnderssonO, AdamsBA, YooD, EllisGC, GutP, AndersonRM, et al. Adenosine signaling promotes regeneration of pancreatic β cells in vivo. Cell Metab2012;15:88594. Search in Google Scholar

28. SharmaAK, BhartiS, KumarR, KrishnamurthyB, BhatiaJ, KumariS, et al. Syzygium cumini ameliorates insulin resistance and β-cell dysfunction via modulation of PPAR, dyslipidemia, oxidative stress, and TNF-α in type 2 diabetic rats. J Pharmacol Sci2012;119:20513. Search in Google Scholar

29. AchrekarS, KaklijGS, PoteMS, KelkarSM. Hypoglycemic activity of Eugenia jambolana and Ficus bengalensis: mechanism of action. In Vivo1991;5:1437. Search in Google Scholar

30. RizviSI, TraditionalMN. Indian medicines used for the management of diabetes mellitus. J Diabetes Res2013;2013:712092. Search in Google Scholar

31. TeixeiraCC, PintoLP, KesslerFH, KnijnikL, PintoCP, GastaldoGJ, et al. The effect of Syzygium cumini (L.) Skeels on post-prandial blood glucose levels in non-diabetic rats and rats with streptozotocin-induced diabetes mellitus. J Ethnopharmacol1997;56:20913. Search in Google Scholar

32. OliveiraAC, EndringerDC, AmorimLA, BrandãoMG, CoelhoMM. Effect of the extracts and fractions of Baccharis trimera and Syzygium cumini on glycaemia of diabetic and non-diabetic mice. J Ethnopharmacol2005;102:4659. Search in Google Scholar

Received: 2015-2-10
Accepted: 2015-4-21
Published Online: 2015-5-8
Published in Print: 2015-9-1

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