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Evaluation of in vivo hypoglycemic potential of 4-ethyloxychalcone in alloxan-induced diabetic rats

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Abstract

The presently available therapies for type 2 diabetes have not been able to achieve normoglycemic status in a majority of the patients which may be either due to the limitations of the drug itself or its side effects. In an effort to develop potent and safe oral antidiabetic agents, 4-ethyloxychalcone, which was found to be the most potent antiglycating agent in our previous study, has been evaluated for its in vivo hypoglycemic activity using an alloxanized diabetic rat model. The diabetes was induced in rats by injection of intraperitoneal alloxan. However, the oral route was used for the administration of 4-ethyloxychalcone. A significant glucose-lowering effect (P < 0.05) comparable with the standard glibenclamide has been observed for 4-ethyloxychalcone in an oral glucose tolerance test. 4-Ethyloxychalcone also produced a significant decrease (P < 0.05) in fasting blood glucose levels during the 42 days of treatment. Furthermore, a significant lowering (P < 0.05) of glycated hemoglobin (HbA1C ) level was also shown by 4-ethyloxychalcone after 42 days of treatment. Thus, 4-ethyloxychalcone might be regarded as a potential hypoglycemic agent that can act as a platform for the development of future antidiabetic drugs.

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References

  1. L.J. Gray, J. Dales, E.M. Brady, K. Khunti, W. Hanif, M.J. Davies, Safety and effectiveness of non-insulin glucose-lowering agents in the treatment of people with type 2 diabetes who observe Ramadan: a systematic review and meta-analysis. Diabetes Obes. Metab. 17, 639–648 (2015)

    Article  CAS  Google Scholar 

  2. M.G. Lepard, A.L. Joseph, A.A. Agne, A.L. Cherrington, Diabetes self-management interventions for adults with type 2 diabetes living in rural areas: a systematic literature review. Curr. Diabetes Rep. 15(6), 1–12 (2015)

    Article  CAS  Google Scholar 

  3. J.W. Stevens, K. Khunti, R. Harvey, M. Johnson, L. Preston, H.B. Woods, M. Davies, E. Goyder, Preventing the progression to Type 2 diabetes mellitus in adults at high risk: a systematic review and network meta-analysis of lifestyle, pharmacological and surgical interventions. Diabetes Res. Clin. Pract. 107, 320–331 (2015)

    Article  CAS  Google Scholar 

  4. S.J. Chen, C. Aikawa, T. Matsui, Quantitative analysis of methylglyoxal, glyoxal and free advanced glycation end-products in the plasma of wistar rats during the oral glucose tolerance test. Biol. Pharm. Bull. 38, 336–339 (2015)

    Article  CAS  Google Scholar 

  5. S. Menini, C. Iacobini, C. Ricci, C.B. Fantauzzi, G. Pugliese, Protection from diabetes-induced atherosclerosis and renal disease by d-carnosine-octylester: effects of early vs late inhibition of advanced glycation end-products in Apoe-null mice. Diabetologia 58, 845–853 (2015)

    Article  CAS  Google Scholar 

  6. M. Brownlee, Biochemistry and molecular cell biology of diabetic complications. Nature 414, 813–820 (2001)

    Article  CAS  Google Scholar 

  7. A.M. Schmidt, S.D. Yan, S.F. Yan, D.M. Stern, The biology of the receptor for advanced glycation end products and its ligands. Biochim. Biophys. Acta-Mol Cell Res. 1498, 99–111 (2000)

    Article  CAS  Google Scholar 

  8. T. Takeuchi, O. Tsutsumi, Y. Ikezuki, Y. Takai, Y. Taketani, Positive relationship between androgen and the endocrine disruptor, bisphenol A, in normal women and women with ovarian dysfunction. Endocr. J. 51, 165–169 (2004)

    Article  CAS  Google Scholar 

  9. K.M. Khan, M. Taha, F. Rahim, M.I. Fakhri, W. Jamil, M. Khan, S. Rasheed, A. Karim, S. Perveen, M.I. Choudhary, Acylhydrazide Schiff Bases: synthesis and antiglycation activity. J. Chem. Soc. Pak. 35, 929–937 (2013)

    Google Scholar 

  10. J.M. Gamble, A. Clarke, K.J. Myers, M.D. Agnew, K. Hatch, M.M. Snow, E.M. Davis, Incretin-based medications for type 2 diabetes: an overview of reviews. Diabetes Obes. Metab. 17, 649–658 (2015)

    Article  CAS  Google Scholar 

  11. R.S. Rita, K. Dezaki, T. Kurashina, M. Kakei, T. Yada, Partial blockade of Kv2.1 channel potentiates GLP-1’s insulinotropic effects in islets and reduces its dose required for improving glucose tolerance in type 2 diabetic male mice. Endocrinology 156, 114–123 (2015)

    Article  Google Scholar 

  12. W.M. Valenciaand, H. Florez, Pharmacological treatment of diabetes in older people. Diabetes Obes. Metab. 16, 1192–1203 (2014)

    Article  Google Scholar 

  13. V. Eapen, D. Shiers, J. Curtis, Bridging the gap from evidence to policy and practice: reducing the progression to metabolic syndrome for children and adolescents on antipsychotic medication. Aust. N. Z. J. Psychiatry 47, 435–442 (2013)

    Article  Google Scholar 

  14. K.L. Edward, B. Rasmussen, I. Munro, Nursing care of clients treated with atypical antipsychotics who have a risk of developing metabolic instability and/or type 2 diabetes. Arch. Psychiatr. Nurs. 24, 46–53 (2010)

    Article  Google Scholar 

  15. T. Deng, H.J. Wang, C. Cai, Application of bis (oxazoline) in asymmetric beta-amination of chalcones. New J. Chem. 39, 102–105 (2015)

    Article  CAS  Google Scholar 

  16. C. Karthikeyan, N.S.H.N. Moorthy, S. Ramasamy, U. Vanam, E. Manivannan, D. Karunagaran, P. Trivedi, Advances in chalcones with anticancer activities. Recent Patient Anti-Cancer Drug Discov. 10, 97–115 (2015)

    Article  CAS  Google Scholar 

  17. G.A. Meshramand, V.A. Vala, Synthesis, characterization, and antimicrobial activity of benzimidazole-derived chalcones containing 1,3,4-oxadiazole moiety. Chem. Heterocycl. Compd. 51, 44–50 (2015)

    Article  Google Scholar 

  18. B.I. Roman, T. De Ryck, S. Verhasselt, M.E. Bracke, C.V. Stevens, Further studies on anti-invasive chemotypes: an excursion from chalcones to curcuminoids. Bioorg. Med. Chem. Lett. 25, 1021–1025 (2015)

    Article  CAS  Google Scholar 

  19. M.J. Matos, S. Vazquez-Rodriguez, E. Uriarte, L. Santana, Potential pharmacological uses of chalcones: a patent review (from June 2011–2014). Expert Opin. Ther. Patents 25, 351–366 (2015)

    Article  CAS  Google Scholar 

  20. P. Singh, A. Anand, V. Kumar, Recent developments in biological activities of chalcones: a mini review. Eur. J. Med. Chem. 85, 758–777 (2014)

    Article  CAS  Google Scholar 

  21. M. Ritter, R.M. Martins, D. Dias, C.M.P. Pereira, Recent advances on the synthesis of chalcones with antimicrobial activities: a brief review. Lett. Org. Chem. 11, 498–508 (2014)

    Article  CAS  Google Scholar 

  22. Z. Nowakowska, A review of anti-infective and anti-inflammatory chalcones. Eur. J. Med. Chem. 42, 125–137 (2007)

    Article  CAS  Google Scholar 

  23. D.K. Mahapatra, V. Asati, S.K. Bharti, Chalcones and their therapeutic targets for the management of diabetes: structural and pharmacological perspectives. Eur. J. Med. Chem. 92, 839–865 (2015)

    Article  CAS  Google Scholar 

  24. S.M. Gomha, S.M. Riyadha, M.M. Abdalla, Solvent-drop grinding method: efficient synthesis, DPPH radical scavenging and anti-diabetic activities of chalcones, bis-chalcones, azolines, and bis-azolines. Curr. Org. Synth. 12, 220–228 (2015)

    Article  CAS  Google Scholar 

  25. T. Enoki, H. Ofinogi, K. Nagamine, Y. Kudo, K. Sugiyama, M. Tanabe, E. Kobayashi, H. Sagawa, I. Kato, Antidiabetic activities of chalcones isolated from a Japanese herb, Angelica keiskei. J. Agric. Food Chem. 55, 6013–6017 (2007)

    Article  CAS  Google Scholar 

  26. K. Kawanishi, H. Ueda, M. Moriyasu, Aldose reductase inhibitors from the nature. Curr. Med. Chem. 10, 1353–1374 (2003)

    Article  CAS  Google Scholar 

  27. A. Abbas, S. Kalsoom, T.B. Hadda, M.M. Naseer, Evaluation of 4-alkoxychalcones as a new class of antiglycating agents: a combined experimental and docking study. Res. Chem. Intermed. 41, 6443–6462 (2015)

    Article  CAS  Google Scholar 

  28. A. Hussain, M.K. Kashif, M.M. Naseer, U.A. Rana, S. Hameed, Synthesis and in vivo hypoglycemic activity of new imidazolidine-2,4-dione derivatives. Res. Chem. Intermed. 41, 7313–7326 (2015)

    Article  CAS  Google Scholar 

  29. T.M. Babar, M.M. Naseer, F.I. Ali, N.H. Rama, T. Ben Hadda, Synthesis and effect of substituent position on anti-inflammatory activity of 3-(halobenzyl) isocarbostyrils. Med. Chem. Res. 23, 4607–4618 (2014)

    Article  CAS  Google Scholar 

  30. T.M. Babar, M.M. Naseer, M.K. Rauf, H. Pervez, M. Ebihara, N.H. Rama, Synthesis of hexacyclic fused isocoumarin framework through selective domino multicyclizations under catalyst and solvent free conditions. Chin. Chem. Lett. 25, 1282–1286 (2014)

    Article  CAS  Google Scholar 

  31. F. Anam, A. Abbas, K.M. Lo, Zia-ur-Rehman, S. Hameed, M.M. Naseer, Homologous 1,3,5-triarylpyrazolines: synthesis, CH···π interactions guided self-assembly and effect of alkyloxy chain length on DNA binding properties. New J. Chem. 38, 5617–5625 (2014)

    CAS  Google Scholar 

  32. A. Abbas, M.M. Naseer, Synthesis and anti-inflammatory activity of new N-acyl-2-pyrazolines bearing homologous alkyloxy side chains. Acta Chim. Slov. 61, 792–802 (2014)

    CAS  Google Scholar 

  33. K.L. Joyand, R. Kuttan, Anti-diabetic activity of Picrorrhiza kurroa extract. J. Ethnopharmacol. 67, 143–148 (1999)

    Article  Google Scholar 

  34. J. Naowaboot, P. Pannangpetch, V. Kukongviriyapan, B. Kongyingyoes, U. Kukongviriyapan, Antihyperglycemic, antioxidant and antiglycation activities of mulberry leaf extract in streptozotocin-induced chronic diabetic rats. Plant Foods Hum. Nutr. 64, 116–121 (2009)

    Article  CAS  Google Scholar 

  35. E.H. Alberton, R.G. Damazio, L.H. Cazarolli, L.D. Chiaradia, P.U. Leal, R.J. Nunes, R.A. Yunes, F.R.M.B. Silva, Influence of chalcone analogues on serum glucose levels in hyperglycemic rats. Chem. Biol. Interact. 171, 355–362 (2008)

    Article  CAS  Google Scholar 

  36. R.G. Damazio, A.P. Zanatta, L.H. Cazarolli, L.D. Chiaradia, A. Mascarello, R.J. Nunes, R.A. Yunes, F.R.M.B. Silva, Antihyperglycemic activity of naphthylchalcones. Eur. J. Med. Chem. 45, 1332–1337 (2010)

    Article  CAS  Google Scholar 

  37. M. Najafian, A. Ebrahim-Habibi, P. Yaghmaei, K. Parivar, B. Larijani, Core structure of flavonoids precursor as an antihyperglycemic and antihyperlipidemic agent: an in vivo study in rats. Acta Biochim. Pol. 57, 553–560 (2010)

    CAS  Google Scholar 

  38. A. Andrade-Cettoand, H. Wiedenfeld, Hypoglycemic effect of Cecropia obtusifolia on streptozotocin diabetic rats. J. Ethnopharmacol. 78, 145–149 (2001)

    Article  Google Scholar 

  39. S. Lenzen, The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 51, 216–226 (2008)

    Article  CAS  Google Scholar 

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Murtaza, B., Abbas, A., Aslam, A. et al. Evaluation of in vivo hypoglycemic potential of 4-ethyloxychalcone in alloxan-induced diabetic rats. Res Chem Intermed 42, 4161–4170 (2016). https://doi.org/10.1007/s11164-015-2266-0

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