SYNTHESIS AND EVALUATION OF ANTIDIABETIC PROPERTIES OF A ZINC MIXED LIGAND COMPLEX IN HIGH-FAT DIET - LOW-DOSE STREPTOZOTOCIN-INDUCED DIABETIC RATS

Authors

  • Muruganantham Koothappan Department of Biochemistry, University of Madras, Guindy Campus, Chennai – 600 025, Tamil Nadu, India.
  • Roshana Devi Vellai Department of Biochemistry, University of Madras, Guindy Campus, Chennai – 600 025, Tamil Nadu, India.
  • Iyyam Pillai Subramanian Department of Chemistry, Pachaiyappa’s College, Chennai – 600 030, Tamil Nadu, India.
  • Subramanian Sorimuthu Pillai Department of Biochemistry, University of Madras, Guindy Campus, Chennai – 600 025, Tamil Nadu, India.

DOI:

https://doi.org/10.22159/ajpcr.2018.v11i5.24870

Keywords:

Diabetes, Zinc complexes, Metformin-3-hydroxyflavone, Spectral studies, Antidiabetic properties

Abstract

Objective: Due to the multifactorial and multisystemic nature of diabetes mellitus (DM), it is often treated with a combination of therapeutic agents. Earlier, we have synthesized and characterized several organozinc complexes and evaluated their safety and antidiabetic properties in experimental DM. In the present study, a new zinc mixed ligand (metformin-3-hydroxyflavone) was synthesized and characterized by various spectral studies and its antidiabetic properties were evaluated in high-fat diet (HFD) fed – low-dose streptozotocin (STZ)-induced Type 2 D (T2D) in rats.

Methods: The zinc mixed ligand complex was characterized by spectral studies. The toxicity and dosage fixation studies were carried out as per OECD guidelines 423. HFD fed low-dose STZ-induced T2DM in rats was used as the experimental model. The hypoglycemic efficacy of the complex was evaluated through oral glucose tolerance test, homeostasis model assessment of insulin resistance (IR), QUICK I and by determining the status of important biochemical parameters. The activities of marker enzymes such as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were assayed. Metformin was used as a standard drug.

Results: The spectral data evidenced the synthesis of a new zinc mixed ligand complex. The biochemical studies evidenced that the oral administration of the complex at a concentration of 10 mg/kg b.w/rat/day for 30 days to diabetic rats significantly improved the glucose homeostasis which was comparable to metformin treatment (50 mg/kg b.w).

Conclusion: The zinc mixed complex possesses significant antidiabetic properties in ameliorating IR and stimulatory properties.

Downloads

Download data is not yet available.

References

American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010;33 Suppl 1:S62-9.

International Diabetes Federation. IDF Diabetes Atlas. 7th ed. Brussels, Belgium: International Diabetes Federation; 2015.

Tabish SA. Is diabetes becoming the biggest epidemic of the twenty-first century? Int J Health Sci (Qassim) 2007;1:V-VIII.

Thulé PM. Mechanisms of current therapies for diabetes mellitus Type 2. Adv Physiol Educ 2012;36:275-83.

Redmon B, Caccamo D, Flavin P, Michels R, O’Connor P, Roberts J, et al. Diagnosis and Management of Type 2 Diabetes Mellitus in Adults. Bloomington (MN): Institute for Clinical Systems Improvement (ICSI); 2014. p. 85.

Ramakrishna A, Ravishankar GA. Influence of abiotic stress signals on secondary metabolites in plants. Plant Signal Behav 2011;6:1720-31.

Pandey A, Tripathi P, Pandey R, Srivatava R, Goswami S. Alternative therapies useful in the management of diabetes: A systematic review. J Pharm Bioall Sci 2011;3:504-12.

Cornard JP, Merlin JC. Comparison of the chelating power of hydroxyflavones. J Mol Struct 2003;651-653:381-7.

Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 1996;20:933-56.

Witters LA. The blooming of the French lilac. J Clin Invest 2001;108:1105-7.

Maruthur NM, Tseng E, Hutfless S, Wilson LM, Suarez-Cuervo C, Berger Z, et al. Diabetes medications as monotherapy or metformin-based combination therapy for Type 2 diabetes: A systematic review and meta-analysis. Ann Intern Med 2016;164:740-51.

Quaile MP, Melich DH, Jordan HL, Nold JB, Chism JP, Polli JW, et al. Toxicity and toxicokinetics of metformin in rats. Toxicol Appl Pharmacol 2010;243:340-7.

Tsuji A, Sakurai H. Vanadyl ion suppresses nitric oxide production from peritoneal macrophages of streptozotocin-induced diabetic mice. Biochem Biophys Res Commun 1996;226:506-11.

Maanvizhi S, Boppana T, Krishnan C, Arumugam G. Metal complexes in the management of diabetes mellitus: A new therapeutic strategy. Int J Pharm Pharm Sci 2014;6:40-4.

Vijayaraghavan K, Iyyam Pillai S, Subramanian SP. Design, synthesis and characterization of zinc-3 hydroxy flavone, a novel zinc metallo complex for the treatment of experimental diabetes in rats. Eur J Pharmacol 2012;680:122-9.

Sendrayaperumal V, Iyyam Pillai S, Subramanian S. Design, synthesis and characterization of zinc-morin, a metal flavonol complex and evaluation of its antidiabetic potential in HFD-STZ induced Type 2 diabetes in rats. Chem Biol Interact 2014;219:9-17.

Maheswari JU, Pillai SI, Subramanian SP. Zinc-silibinin complex: Synthesis, spectral characterization and biochemical evaluation of antidiabetic potential in high fat fed low dose STZ induced Type 2 diabetic rats. J Chem Pharm Res 2015;7:2051-64.

Gopalakrishnan V, Pillai SI, Subramanian SP. Synthesis, spectral characterization and biochemical evaluation of antidiabetic properties of a new zinc-diosmin complex studied in high fat diet fed-low dose streptozotocin induced experimental Type 2 diabetes in rats. Biochem Res Int 2015;2015:350829.

Srinivasan K, Viswanad B, Asrat L, Kaul CL, Ramarao P. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: A model for type 2 diabetes and pharmacological screening. Pharmacol Res 2005;52:313-20.

Prabhakar PK, Doble M. Effect of natural products on commercial oral antidiabetic drugs in enhancing 2-deoxyglucose uptake by 3T3-L1 adipocytes. Ther Adv Endocrinol Metab 2011;2:103-14.

Panchal I, Sen DJ, Navle A, Shah U. Structure-based drug designing, scoring, and synthesis of some substituted sulphonylureas/guanidine-based derivatives as hypoglycemic agents. Int J Pharm Pharm Sci 2017;9:226-32.

Vella S, Buetow L, Royle P, Livingstone S, Colhoun HM, Petrie JR, et al. The use of metformin in Type 1 diabetes: A systematic review of efficacy. Diabetologia 2010;53:809-20.

Komoroski B, Vachharajani N, Feng Y, Li L, Kornhauser D, Pfister M, et al. Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with Type 2 diabetes mellitus. Clin Pharmacol Ther 2009;85:513-9.

Retnakaran R, Qi Y, Harris SB, Hanley AJ, Zinman B. Changes over time in glycemic control, insulin sensitivity, and beta-cell function in response to low-dose metformin and thiazolidinedione combination therapy in patients with impaired glucose tolerance. Diabetes Care 2011;34:1601-4.

Dujic T, Zhou K, Donnelly LA, Tavendale R, Palmer CN, Pearson ER, et al. Association of organic cation transporter 1 with intolerance to metformin in Type 2 diabetes: A GoDARTS study. Diabetes 2015;64:1786-93.

Zhu M, Lu L, Yang P, Jinb X. Bis(1,1-dimethylbiguanido)nickel(II). Acta Crystallogr Sect 2002;58:272-4.

Enyedy EA, Hollender D, Kiss T. Lipophilicity of kinetically labile metal complexes through the example of antidiabetic zn(II) and VO(IV) compounds. J Pharm Biomed Anal 2011;54:1073-81.

Sobola AO, Watkins GM, Brecht BV. Synthesis, characterization and antimicrobial activity of copper(II) complexes of some ortho-substituted aniline schiff bases; Crystal structure of bis(2-methoxy-6- imino)methylphenol copper(II) complex. Afr J Chem 2014;67:45-51.

Saydam S, Yilmaz E. Synthesis, characterization and thermal behavior of 4-chloromethyl-2-(2-hydroxybenzilidenehydrazino) thiazole and its complexes with cr(III), co(II), ni(II) and cu(II). Spectrochim Acta A Mol Biomol Spectrosc 2006;63:506-10.

Ferraro JR. Low-Frequency Vibrations of Inorganic and Coordination Compounds. New York: Plenum Press; 1971.

Tas E, Aslanoglu M, Guler M, Ulusoy M. Synthesis, characterization and electrochemical properties of copper(II) complexes with novel bidentate salicylaldimines derived from 3,5-DI-t-butyl-2- hydroxybenzaldehyde. J Coord Chem 2004;57:583-9.

Reed MJ, Meszaros K, Entes LJ, Claypool MD, Pinkett JG, Gadbois TM, et al. A new rat model of Type 2 diabetes: The fat-fed, streptozotocin-treated rat. Metabolism 2000;49:1390-4.

Wilcox G. Insulin and insulin resistance. Clin Biochem Rev 2005;26:19- 39.

Stumvoll M, Mitrakou A, Pimenta W, Jenssen T, Yki-Järvinen H, Van Haeften T, et al. Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care 2000;23:295-301.

Clark SL, Santin AE, Bryant PA, Holman R, Rodnick KJ. The initial noncovalent binding of glucose to human hemoglobin in nonenzymatic glycation. Glycobiology 2013;23:1250-9.

Florkowski C. HbA1c as a diagnostic test for diabetes mellitus-reviewing the evidence. Clin Biochem Rev 2013;34:75-83.

Wajchenberg BL. Beta-cell failure in diabetes and preservation by clinical treatment. Endocr Rev 2007;28:187-218.

Cerf ME. Beta cell dysfunction and insulin resistance. Front Endocrinol (Lausanne) 2013;4:37.

Sallie R, Tredger JM, Williams R. Drugs and the liver. Part 1: Testing liver function. Biopharm Drug Dispos 1991;12:251-9.

Jaiganesh C, Devi VR, Pillai SI, Subramanian S. Synthesis, characterization And evaluation of antidiabetic properties of a new metformin-3-hydroxyflavone complex studied in high fat diet fed-low dose streptozotocin induced experimental Type 2 diabetes in wistar rats. Int J Pharm BioSci 2017;8:1-15.

Jaiganesh C, Subramanian S. Metformin-3-hydroxyflavone, a new schiff base complex modulates the activities of carbohydrate regulatory enzymes in high fat diet fed-low dose streptozotocin induced Type 2 diabetes in experimental rats. J Chem Pharm Res 2017;9:90-100.

Published

01-05-2018

How to Cite

Koothappan, M., R. Devi Vellai, I. Pillai Subramanian, and S. Sorimuthu Pillai. “SYNTHESIS AND EVALUATION OF ANTIDIABETIC PROPERTIES OF A ZINC MIXED LIGAND COMPLEX IN HIGH-FAT DIET - LOW-DOSE STREPTOZOTOCIN-INDUCED DIABETIC RATS”. Asian Journal of Pharmaceutical and Clinical Research, vol. 11, no. 5, May 2018, pp. 429-38, doi:10.22159/ajpcr.2018.v11i5.24870.

Issue

Section

Original Article(s)