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

摘要

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.