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

Eurycoma longifolia has been widely used by society as an aphrodisiac especially in Indonesia, Vietnam and Malaysia. However, only few studies have been published related to the herb-drug interaction. Previous study showed that the standardized extract of E. longifolia affected phase I rosiglitazone metabolism especially in the old male rat hepatocytes for both diabetic and normal rats. The present study evaluated the possible mechanism of E. longifolia extract in affecting of phase I rosiglitazone metabolism in the old normal male rat hepatocytes.  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 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 0.001-100µg/mL of E. longifolia extract). Effect of E. longifolia extract on phase I rosiglitazone metabolism was determined by colourimetric method of Nash at 415nm. The results showed the significant effect of E. longifolia extract on rosiglitazone metabolism were found after rat hepatocytes were pretreated with okadaic acid and genistein. No significant effect was observed in the presence of KT5823, KT5720, furafyllin, L-ornithine, trifluoperazine, 3-isobutyl-methylxanthine/IBMX, phorbol-12-myristate-13-acetate/PMA and guanylyl-5’-imidodiphosphate/Gpp. This 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.