Molecular docking of citrus flavonoids with some targets related to diabetes

  • Wei Shen State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai
  • Yan-Hua Lu State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai
Keywords: Citrus flavonoid, Docking analysis, Diabetes mellitus

Abstract

Citrus flavonoids isolated from citrus peel (flavedo and albedo) were taken as ligands for molecular docking. The molecular targets, (i.e. glucokinase, glycogen synthase kinases 3?, peroxisome proliferator-activated receptor gamma, and dipeptidyl peptidase IV) whose crystallographic structures are available on the PDB database as 1V4S, 1Q4L, 2PRG, 2ONC respectively, were used for the docking analysis using the Autodock tool V 4.2 and ADT v1.5.4 programs. The docking studies of the ligands citrus flavonoids with four different target proteins showed that citrus flavonoids are good molecules which dock well with various targets related to diabetes mellitus. The above results demonstrate that citrus flavonoids might be potentially used for blood glucose regulation. 

Downloads

Download data is not yet available.
Abstract
2934
Download
2107 Read
595

References

Abu-Hamdah R, Rabiee A, Meneilly GS, Shannon RP, Andersen DK, Elahi D. The extra-pancreatic effects of glucagon-like peptide-1 and related peptides. J Clin Endocrinol Metab. 2009; 94: 1843-52.

Akhtar M, Bharatam PV. 3D-QSAR and molecular docking studies on 3-anilino-4-arylmaleimide derivatives as glycogen synthase kinase-3? inhibitors. Chem Biol Drug Design. 2012; 79: 560-71.

Akiyama S, Katsumata S, Suzuki K, Nakaya Y, Ishimi Y, Uehara M. Hypoglycemic and hypolipidemic effects of hesperidin and cyclodextrin-clathrate hesperetin in Goto-Kakizaki rats with type 2 diabetes. Biosci Biotechnol Biochem. 2009; 73: 2779-82.

Akiyama S, Katsumata S, Suzuki K, Ishimi Y, Wu J, Uehara M. Dietary hesperidin exerts hypoglycemic and hypolipidemic effects in streptozotocin-induced marginal type 1 diabetic rats. J Clin Biochem Nutr. 2010; 46: 87-92.

Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007; 132: 2131-57.

Balamurugan R, Stalin A, Ignacimuthu S. Molecular docking of ?-sitosterol with some targets related to diabetes. Eur J Med Chem. 2012; 47: 38-43.

Benavente-Garcia O, Castillo J. Update on uses and properties of citrus flavonoids: New findings in anticancer, cardiovascular, and anti-inflammatory activity. J Agric Food. 2008; 2: 6185-205.

Bruning JB, Chalmers MJ, Prasad S, Busby SA, Kamenecka TM, He Y, Nettles KW, Griffin PR. Partial agonists activate PPARgamma using a helix 12 independent mechanism. Structure 2007; 15: 1258-71.

Chandramohan C, Ignacimuthu S, Pugalendi KV. A novel compound from Casearia esculenta (Roxb.) root and its effect on carbohydrate metabolism in streptozotocin-diabetic rats. Eur J Pharmacol. 2008; 590: 437-43.

Choi EJ, Ahn WS. Neuroprotective effects of chronic hesperetin administration in mice. Arch Pharm Res. 2008; 31: 1457-62.

Choi JH, Banks AS, Kamenecka TM et al. Antidiabetic actions of a non-agonist PPAR? ligand blocking Cdk5-mediated phosphorylation. Nature 2011; 477: 477-81.

Deacon CF. Therapeutic strategies based on glucagon-like peptide 1. Diabetes 2004; 53: 2181-89.

Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006. 368: 1696-705.

Johnson JL, Rupasinghe SG, Stefani, F, Schuler MA, Gonzalez de Mejia E. Citrus flavonoids luteolin, apigenin, and quercetin inhibit glycogen synthase kinase-3? enzymatic activity by lowering the interaction energy within the binding cavity. J Med Food. 2011; 14: 325-33.

Jung UJ, Lee MK, Jeong KS, Choi MS. The hypoglycemic effects of hesperidin and naringin are partly mediated by hepatic glucose-regulating enzymes in C57BL/KsJ-db/db mice. J Nutri. 2004; 4: 2499-503.

Jung UJ, Lee MK, Park YB, Kang MA, Choi MS. Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA levels in type-2 diabetic mice. Int J Biochem Cell Biol. 2006; 38: 1134-45.

Kamata K, Mitsuya M, Nishimura T, Eiki J, Nagata Y. Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase. Structure 2004; 12: 429-38.

Khanfar MA, Hill RA, Kaddoumi A, El Sayed KA. Discovery of novel GSK-3? inhibitors with potent in vitro and in vivo activities and excellent brain permeability using combined ligand- and structure-based virtual screening. J Med Chem. 2010; 53: 8534-45.

Lee YS, Cha BY, Saito K et al. Nobiletin improves hyperglycemia and insulin resistance in obese diabetic ob/ob mice. Biochem Pharmacol. 2010; 79: 1674-83.

Liu Q, Chen L, Hu L, Shen X. Small molecules from natural sources, targeting signaling pathways in diabetes. Biochim Biophys Acta. 2010; 1799: 854-65.

Maltarollo VG, Honório KM. Ligand- and structure-based drug design strategies and PPAR?/? selectivity. Chem Biol Drug Design. 2012; 80: 533-44.

Manthey JA, Grohmann K, Guthrie N. Biological properties of citrus flavonoids pertaining to cancer and inflammation. Curr Med Chem. 2001; 8: 135-53.

Nolte RT, Wisely GB, Westin S, Cobb JE, lambert MH, Kurokawa R, Rosenfeld MG, Wilson TM, Glass CK, Milburn MV. Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-?. Nature 1998; 16: 137-143.

Osguthorpe DJ, Sherman W, Hagler AT. Generation of receptor structural ensembles for virtual screening using binding site shape analysis and clustering. Chem Biol Drug Des. 2012; 80: 182-93.

Osolodkin DI, Palyulin VA, Zefirov NS. Structure-based virtual screening of glycogen synthase kinase 3? inhibitors: analysis of scoring functions applied to large true actives and decoy sets. Chem Biol Drug Des. 2011; 78: 378-90.

Parmar HS, Jain P, Chauhan DS, Bhinchar MK, Munjal V, Yusuf M, Choube K, Tawani A, Tiwari V, Manivannan E, Kumar A. DPP-IV inhibitory potential of naringin: An in silico, in vitro and in vivo study. Diabetes Res Clin Pract. 2012; 97: 105-11.

Shen W, Xu Y, Lu YH. Inhibitory effects of citrus flavonoids on starch digestion and antihyperglycemic effects in HepG2 cells. J Agric Food Chem. 2012; 60: 9609-19.

Stoffel M, Froguel PH, Takeda J, Zouali H, el al. Human glucokinase gene: Isolation, characterization, and identification of two missense mutations linked to early-onset non-insulin-dependent (type 2) diabetes mellitus. Proc Natl Acad Sci. 1992; 89: 7698-702.

Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: Principles of pathogenesis and therapy. Lancet 2005; 365: 1333-46.

Verspohl EJ. Novel therapeutics for type 2 diabetes: incretin hormone mimetics (glucagon-like peptide-1 receptor agonists) and dipeptidyl peptidase-4 inhibitors. Pharmacol Ther. 2009; 124: 113-38.

Published
2013-04-19
How to Cite
Shen, W., and Y.-H. Lu. “Molecular Docking of Citrus Flavonoids With Some Targets Related to Diabetes”. Bangladesh Journal of Pharmacology, Vol. 8, no. 2, Apr. 2013, pp. 156-70, doi:10.3329/bjp.v8i2.14240.
Section
Research Articles