EFFECT OF STANDARDIZED EURYCOMA LONGIFOLIA EXTRACT ON PHASE I ROSIGLITAZONE METABOLISM IN THE OLD NORMAL MALE RAT HEPATOCYTES: A MECHANISM STUDY

  • Purwantiningsih . Faculty of Pharmacy, Gadjah Mada University
  • Abas Hj Hussin Gadjah Mada University
  • Kit Lam Chan Gadjah Mada University

Abstract

Objective: The aim of present study was to evaluate the possible mechanism of E. longifolia extract in affecting phase I Rosiglitazone metabolism in the old normal male rat hepatocytes.

Methods: Experiment was performed used ten cellular stimulants/inhibitors. Old normal male rats were divided in ten groups (n = 6) and the hepatocytes were isolated using the perfusion technique. Each group had a negative control (in the presence of vehicle), a positive control (in the presence of cellular inhibitors/stimulants) and 6 test subgroups (in the presence of cellular inhibitors/stimulants and 0.001-100 µg. .mL-1 of E. longifolia extract). Effect of E. longifolia extract on phase I Rosiglitazone metabolism was determined by the colorimetric method of Nash at 415 nm.

Results: The results showed a significant effect of E. longifolia extract on phase I Rosiglitazone metabolism was observed after rat hepatocytes were pretreated with okadaic acid and genistein. After pre-incubation with KT5823 and trifluoperazine /TPA, the significant effect was only found in the presence of E. longifolia extract at the highest concentration (100 µg. .mL-1) and no significant effect was observed in the presence of KT5720, furafyllin, L-ornithine, 3-isobutyl-methylxanthine/IBMX, phorbol-12-myristate-13-acetate/PMA and guanylyl-5’-imidodiphosphate/Gpp.

Conclusion: The data suggested that the possible effect of E. longifolia extract on phase I Rosiglitazone metabolism in the old normal male rats was probably mediated through the activation of phosphatase and inhibition of tyrosine kinases.

 

Keywords: Rosiglitazone, Eurycoma longifolia, Old normal male rat, Mechanism study, Stimulant/inhibitor

Downloads

Download data is not yet available.

References

1. Ingelman-Sundberg M, Sim SC, Gomez A, Rodriguez-Antona C. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Therapeut 2007;116(3):496-526.
2. Oesch-Bartlomowicz B, Oesch F. Phosphorylation of cytochromes P450:First discovery of a posttranslational modification of a drug-metabolizing enzyme. Biochem Biophys Res Commun 2005;338(1):446-9.
3. Pelkonen O, Turpeinen M, Hakkola J, Honkakoski P, Hukkanen J, Raunio H. Inhibition and induction of human cytochrome P450 enzymes: current status. Arch Toxicol 2008;82(10):667-715.
4. Zhou S, Chan E, Pan SQ, Huang M, Lee EJ. Pharmacokinetic interactions of drugs with St John's wort. J Psychopharmacol 2004;18(2):262-76.
5. Le-Bigot JF, Begue JM, Kiechel JR, Guillouzo A. Species differences in metabolism of ketotifen in rat, rabbit and human: demonstration of similar pathways in vivo and in cultured hepatocytes. Life Sci 1987;40:883-90.
6. Chan KL, Choo CY, Morita H, Itokawa H. High performance liquid chromatography in phytomedical analysis of Eurycoma longifolia. Planta Med 1998;64:741-5.
7. Uji T. Eurycoma longifolia Jack. Plant Resources of South-East Asia In de Padua LS, Bunyapraphatsara N, Lemmens RHMJ, editors. Medicinal and poisonous plants No. 12(1). Leiden, Netherlands: Backhuys Publisher; 1999. p. 274-5.
8. Ang HH, Sim MK. Eurycoma longifolia Jack enhances libido in sexually experienced male rats. J Exp Anim Sci 1997;46:287-90.
9. Lin LC, Peng CY, Wang HS, Lee KW, Paulus WS. Reinvestigation of the chemical constituents of Eurycoma longifolia. Chin Pharm J 2001;53:97-106.
10. Ang HH, Lee KL, Kiyoshi M. Eurycoma longifolia Jack enhances sexual motivation in middle-aged male mice. J Basic Clin Physiol Pharmacol 2003;14:301-8.
11. Chan KL, Choo CY, Abdullah NR, Ismail Z. Antiplasmodial studies of Eurycoma longifolia Jack using the lactate dehydrogenase assay of Plasmodium falciparum. J Ethnopharmacol 2004;92:223-7.
12. Kardono LBS, Angerhofer CK, Tsauri S, Padmawinata K, Pezzuto JM, Kinghorn AD. Cytotoxic and antimalarial constituents of the roots of Eurycoma longifolia. J Nat Prod 1991;54:1360-7.
13. Jiwajinda S, Santisopasri V, Murakami A, Kawanaka M, Kawanaka H, Gasquet M, et al. In vitro anti-tumor promoting and anti-parasitic activities of the quassinoids from Eurycoma longifolia, a medicinal plant in Southeast Asia. J Ethnopharmacol 2002;82:55-8.
14. Salman SAB, Amrah S, Wahab MSA, Ismail Z, Ismail R, Yuen KH, et al. Modification of propranolol’s bioavailability by Eurycoma longifolia water-based extract. J Clin Pharm Ther 2010;35(6):691-6.
15. Purwantiningsih, Hussin AH, Chan KL. Phase I drug metabolism study of the standardised extract of Eurycoma longifolia (TAF-273) in rat hepatocytes. Int J Pharm Pharm Sci 2010;2 (suppl 3):147-52.
16. Purwantiningsih, Hussin AH, Chan KL. Herb-Drug interaction studies of eurycoma longifolia extract taf-273 on the metabolism of Rosiglitazone, an antidiabetic drug. Asian J Pharm Clin Res 2011;4(2):88-92.
17. Pan Y, Tiong KH, Abd-Rashid BA, Ismail Z, Ismail R, Mak JW, et al. Effect of eurycomanone on cytochrome P450 isoforms CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 in vitro. J Nat Med 2013;67(3):794-8.
18. Purwantiningsih, Ismail S, Hussin AH, Chan KL. Inhibitory effect of eurycoma longifolia extract and eurycomanone on human cytochrome p450 isoforms. Int J Pharm Pharm Sci 2014;6(6):441-4.
19. Purwantiningsih, Hussin AH, Chan KL. Herb-Drug interaction studies of eurycoma longifolia extract taf-273 on the metabolism of Rosiglitazone, an antidiabetic drug. Asian J Pharm Clin Res 2011;4(2):88-92.
20. Fioravanti L, Cappelletti V, Miodini P, Ronchi E, Brivio M, Di-Fronzo G. Genistein in the control of breast cancer cell growth: insights into the mechanism of action in vitro. Cancer Lett 1998;130:143-52.
21. Grider JR. Interplay of VIP and nitric oxide in regulation of the descending relaxant agents in isolated gastric muscle cells. Am J Physiol 1993;264:G334-40.
22. Simpson CS, Morris BJ. Induction of c-fos and Zif/268 gene expression in rat striatal neurons, following stimulation of D1-like dopamine receptors, involves protein kinase A and protein kinase C. Neurosci 1995;68:97-106.
23. Hube F, Lee YM, Rohrig K, Hauner H. The phosphodiesterase inhibitor IBMX supresses TNF-alpha expression in human adipocyte precursore cells: a possible explanation for its adipogenic effect. Horm Metab Res 1999;31:665-71.
24. Gonzales-Espinosa C, Garcia-Sainz JA. Protein kinases and phosphatase modulate c-fos expression in rat hepatocytes. Effects of angiotensin II and phorbol myristate acetate. Life Sci 1995;56:723-8.
25. Londos C, Salomon Y, Lin MC, Harwood JP, Schramm M, Wolff J, et al. 5'-Guanylylimidodiphosphate, a potent activator of adenylate cyclase systems in eukaryotic cells. Proc Natl Acad Sci USA 1974;7:3087-90.
26. Biolajan C, Takai A. Inhibitory effect of a marine-sponge toxin, okadaic acid, on protein phosphatase. Biochem J 1988;256:283-90.
27. Kimura S, Nagasaki K, Yamaguchi K, Fujiki H, Abe K. Stimulation of hepatic glycogenolysis by 12-O-tetradecanoylphorbol-13-acetate (TPA) via a calcium requiring process. Biochem Biophys Res Commun 1984;122:1057-64.
28. Dorothea S, Boobis AR, Murray BP, Segura J, De la Torre R, Davies DS. Furafylline is a potent and selective inhibitor of cytochrome P-4501A2 in Man. Br J Clin Pharmacol 1990;29:651-63.
29. Rees DD, Palmer RMJ, Schulz R, Hodson HF, Moncada S. Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Clin Pharmacol 1990;101:746-52.
30. Hussin AH, Skett P. Lack of effect of insulin in hepatocytes isolated from streptozotocin-diabetic male rats. Biochem Pharmacol 1988;37(9):1683-6.
31. Taher YA. Study on traditional medicine-modern drug interaction and its molecular mechanism elucidation in rat liver. Pulau Pinang: University Sains Malaysia; 1998.
32. Nash T. The colorimetric estimation of formaldehyde by means of the Hantzsch reaction. Biochem J 1953;55:416-21.
33. Gibson GG, Skett P. Introduction to Drug Metabolism. 3th ed. Cheltenham: Nelson Thornes Publishers; 2001.
34. Timbrell J. Principles of biochemical toxicology. London: Taylor & Francis Ltd; 2001.
35. Wang YQ, Liao M, Hoe N, Acharya P, Deng C, Krutchinsky AN, et al. Role for Protein Phosphorylation in Cytochrome P450 3A4 Ubiquitin-dependent Proteasomal Degradation. J Biol Chem 2009;284(9):5671-84.
36. Gietzen K, Sadorf I, Bader H. A model for the regulation of the calmodulin-dependent enzymes erythrocyte Ca2+-transport ATPase and brain phosphodiesterase by activators and inhibitors. Biochem J 1982;207:541-8.
37. Akiyama T, Ishida J, Nakagawa S, Ogawara H, Watanabe S, Itoh N. et al. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem 1987;262:5592-5.
38. Abas HH, Saringat HB, Rozana AA. Interaction of Several traditional Medicine Preparations with aminopyrine in rat hepatocytes. ASEAN Review of Biodiversity and Environmental Conservation (ARBEC) 1998;Article V: 1-7 [Online]. [Accessed 14th September 2011]. Available from World Wide Web:http://www.arbec.com.my/pdf/may-5.pdf
39. Han CJ, Hussin AH. Effect of the Orthosiphon stamineus Benth on aminopyrine metabolism in rat hepatocytes. M J P S 2007;5(1):25-32.
40. Chin JH, Mahfoudh M, Abas HH. Interactions of Orthosiphon stamineus and Morinda citrifolia with hepatic aminopyrine metabolism by CYP3A in rats. Pharmacogn Mag 2009;5:55-60.
Statistics
456 Views | 637 Downloads
How to Cite
., P., A. H. Hussin, and K. L. Chan. “EFFECT OF STANDARDIZED EURYCOMA LONGIFOLIA EXTRACT ON PHASE I ROSIGLITAZONE METABOLISM IN THE OLD NORMAL MALE RAT HEPATOCYTES: A MECHANISM STUDY”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 7, no. 2, Dec. 2014, pp. 80-83, https://innovareacademics.in/journals/index.php/ijpps/article/view/3491.
Section
Original Article(s)