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A Study on the Inhibitory potential of DPP-IV Enzyme by apigenin through in silico and in vivo approaches

Author Affiliations

  • 1Department of Biochemistry and Biotechnology, Annamalai University, Chidambaram, Tamil Nadu, INDIA

Res. J. Recent Sci., Volume 4, Issue (IYSC-2015), Pages 22-29, September,2 (2015)

Abstract

Dipeptidyl peptidase-IV (DPP-IV) inhibitors are incretin enhancers used in the treatment of diabetes. Due to their undesirable side effects, development of new agents preferably from natural sources with less adverse effects is needed. Apigenin (API), a well known insulin-secretagogue and insulin-mimetic agent is abundantly present in fruits, nuts and plant derived beverages. The present study investigates the DPP-IV inhibitory potential and antidiabetic effects of API using various approaches. Through in silico study, we showed that API has binding efficacy at Glu206 in the active site of DPP-IV. Plasma glucose and insulin levels were decreased when API (1.5 mg/kg b.w. for every alternate for last 30 days) was administered to high fat, high fructose diet (HFFD) fed rats. Further, the activity of DPP-IV in plasma and hippocampal homogenate was inhibited more in the API- treated group than in the sitagliptin (STG)- treated group. API has a strong inhibitory effect towards DPP-IV enzyme in vivo and in silico and therefore can be a promising compound for type 2 diabetes (T2D) treatment.

References

  1. Ansorge S., Nordhoff K., Bank U., Heimburg A., Julius H., Breyer D., Thielitz A., Reinhold D. and Tager M., Novel aspects of cellular action of dipeptidyl peptidase IV/CD26, Biol.Chem., 392, 153–168 (2011)
  2. Palalau A. I., Tahrani A. A., Piya M. K. and Barnett A.H., DPP-4 inhibitors in clinical practice, Postgrad. Med., 121, 70–100 (2009)
  3. Brian D.G., Clifford J.B. and Peter R.F., Gliptin Therapies for Inhibiting Dipeptidyl Peptidase-4 in Type 2 Diabetes, European Endocrinology, 6(2), 19–25 (2010)
  4. Reaven G. M., Role of insulin resistance in human disease, Diabetes., 37(12), 1595-1607 (1988)
  5. Pratchayasakul W., Kerdphoo S., Petsophonsakul P., Pongchaidecha A., Chattipakorn N. and Chattipakorn S.C., Effects of high-fat diet on insulin receptor function in rat hippocampus and the level of neuronal corticosterone, Life Sciences., 88(3-14), 88619–88627 (2011)
  6. Lindqvist A., Mohapel P., Bouter B., Frielingsdorf H., Pizzo D., Brundin P. and Erlanson-Albertsson C., High-fat diet impairs hippocampal neurogenesis in male rats, Eur. J. Neurol., 13, 1385–1388 (2006)
  7. Geetha R., Yogalakshmi B., Sreeja S., Bhavani K., Anuradha C. V., Troxerutin suppresses lipid abnormalities in the heart of high-fat–high-fructose diet-fed mice, Mol. Cell Biochem., 387(1-2),123-34 (2013)
  8. Bhuvaneswari S., Yogalakshmi B., Sreeja S., Anuradha C. V., Astaxanthin reduces hepatic endoplasmic reticulum stress and nuclear factor-ΞΊB-mediated inflammation in high fructose and high fat diet-fed mice, Cell Stress and Chaperones., 19, 183–191(2014)
  9. Semighini E.P., Resende J.A., De Andrade P., Morais P.A., Carvalho I., Taft C.A., Silva C.H., Using computer-aided drug design and medicinal chemistry strategies in the fight against diabetes, Journal of Biomolecular Structure and Dynamics., 28(5), 787–796 (2011)
  10. Jadav P., Bahekar R., Shah S. R., Patel D., Joharapurkar A., Kshirsagar S., Jain M., Shaikh M. and Sairam K.V., Long-acting peptidomimetics based DPP-IV inhibitors, Bioorganic and Medicinal Chemistry Letters., 22(10), 3516–3521 (2012)
  11. Janardhan S., Homology modeling and molecular docking studies of human DPP8 and DPP9, International Journal of Pharma Research and Development, 2(12), 131–146 (2011)
  12. Cao X., Liu B., Cao W., Zhang W., Zhang F., Zhao H., Meng R., Zhang L., Niu R., Hao X. and Zhang B., Autophagy inhibition enhances apigenin induced apoptosis in human breast cancer cells, Chin. J. Cancer. Res., 25, 212-222 (2013)
  13. Liu Q., Chen X., Yang G., Min X. and Deng M., Apigenin inhibits cell migration through MAPK pathways in human bladder smooth muscle cells, Biocell., 35, 71-79 (2011)
  14. Chowdhury M. H., Miltu K. G., Bhabani S. S., Niladri S. D., Biswajit M., Apigenin causes biochemical modulation, GLUT 4 and CD38 alterations to improve diabetes and to protect damages of some vital organs in experimental diabetes, American Journal of Pharmacology and Toxicology, 9(1), 39-52 (2014)
  15. Liu R., Zhang T., Yang H., Lan X., Ying J. and Du G., The flavonoid apigenin protects brain neurovascular coupling against amyloid-beta25-35-induced toxicity in mice, J. Alzheimers Dis., 24, 85–100 (2011)
  16. Friesner R.A., Banks J.L., Murphy R.B., Beard H.S., Frye L.L., Halgren T.A., Klicic J.J., Mainz D.T., Repasky M. P., Knoll E. H., Shelley M., Perry J. K., Shaw D. E., Francis P., Shenkin P. S., Glide: a new approach for rapid, accurate docking and scoring method and assessment of docking accuracy, J. Med. Chem., 7, 1739–1749 (2004)
  17. Shelley J.C., Cholleti A., Frye L.L., Greenwood J.R., Timlin M.R. and Uchimaya M., Epik: a software program for pK(a) prediction and protonation state generation for drug-like molecules, J. Comput. Aided Mol. Des.,12, 681–691 (2007)
  18. Friesner R.A., Murphy R.B., Repasky M.P., Frye L.L., Greenwood J.R., Halgren T.A., Sanschagrin P.C. and Mainz D.T., Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes, J. Med. Chem., 21, 6177–6196 (2006)
  19. Ohno M., Shibata C., Kishikawa T., Yoshikawa T., Takata A., Kojima K., Akanuma M., Kang Y.J., Yoshida H., Otsuka M. and Koike., The flavonoid apigenin improves glucose tolerance through inhibition of microRNA maturation in miRNA103 transgenic mice, Sci. Rep., 3, 2553-2559 (2013)
  20. Hiranya P., Nattayaporn A., Nipon C. and Siriporn C.C., DPP4 inhibitors improve cognition and brain mitochondrial functions of insulin-resistant rats, Society for Endocrinology., 218(1), 1-11 (2013)
  21. Kreisel W., Heussner R., Volk B., Buchsel R., Reutter W. and Gerok W., Identification of the 110 000 Mr glycoprotein isolated from rat liver plasma membrane as dipeptidylaminopeptidase IV., FEBS. Lett., 147, 85–88 (1982)
  22. Gutt M., Davis C. L., Spitzer S. B., Llabre M.M., Kumar M., Czarnecki E.M., Schneiderman N., Skyler J.S. and Marks J.B., Validation of the insulin sensitivity index (ISI0,120) : comparison with other measures, Diabetes Res. Clin. Pract., 47(3), 177-184 (2000) , 22-29 (2015)
  23. Mentlein R., Dipeptidyl-peptidase IV (CD26)-role in the inactivation of regulatory peptides, Regul. Pept., 85, 9–24 (1999)
  24. Jadav P., Bahekar R., Shah S. R., Patel D., Joharapurkar A., Kshirsagar S., Jain M., Shaikh M. and Sairam K.V., Long-acting peptidomimetics based DPP-IV inhibitors, Bioorganic and Medicinal Chemistry Letters., 22(10), 3516–3521 (2012)
  25. Pissurlenkar R.R.S., Shaikh M.S., Coutinho E.C., 3DQSAR studies of Dipeptidyl peptidase IV inhibitors using a docking based alignment, Journal of Molecular Modeling., 13(10), 1047–1071 (2007)
  26. Kimata H., Fukuda-Tsuru S., Yoshida K., Iwasaki S., Kiuchi S., Akahoshi F. and Ishii S., Teneligliptin, a novel selective dipeptidyl peptidase-4 inhibitor, improves postprandial hyperglycemia in a model of type 2 diabetes, zucker diabetic fatty rats, Med. Consult. New Remedies., 49, 9 (2012)
  27. Fan J., Johnson M.H., Lila M.A., Yousef G. and Mejia E.G., Berry and Citrus Phenolic Compounds Inhibit Dipeptidyl Peptidase IV: Implications in Diabetes Management, Complementary and Alternative Medicine., 2013, 1-13 (2013)
  28. Reddy S. S., Karuna R., Baskar R. and Saralakumari D., Prevention of insulin resistance by ingesting aqueous extract of Ocimum sanctum to fructose-fed rats, Horm. Metab. Res., 40, 44-49 (2008)
  29. Samane S., Christon R., Dombrowski L., Turcotte S., Charrouf Z., Lavigne C., Levy E., Bachelard H., Amarouch H., Marette A. and Haddad P.S., Fish oil and argan oil intake differently modulate insulin resistance and glucose intolerance in a rat model of dietary-induced obesity, Metab. Clin. Exp., 58, 909–919 (2009)
  30. Thirunavukkarasu V. and Anuradha C.V., Influence of lipoic acid on lipid peroxidation and antioxidant defence system in blood of insulin resistant rats, Diabetes Obes. Metab., 6(3), 200–207 (2004)
  31. Chakrabarti R., Bhavtaran S., Narendra P., Varghese N., Vanchhawng L., Shihabudeen M. S. and Thirumurgan K., Dipeptidyl Peptidase- IV Inhibitory Activity of Berberis aristata, Journal of Natural Products., 4, 158-163 (2011)
  32. www.rcsb.org, (2015)
  33. http://www.schrodinger.com, (2015)
  34. www.bioinformatics.leeds.ac.uk/qsitefinder, (2015)