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  • 1 University Sains Malaysia School of Pharmaceutical Sciences 11800 Penang Malaysia
  • 2 University Sains Malaysia Centre for Drug Research 11800 Penang Malaysia
  • 3 Gadjah Mada University Department of Pharmacology & Clinical Pharmacy, Faculty of Pharmacy 55281 Yogyakarta Indonesia
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Previous study showed that the standardised 50% aqueous-methanol extract of Eurycoma longifolia (TAF-273) affected phase 1 aminopyrine metabolism especially in adult male and female rat hepatocytes. The present study evaluated the molecular mechanism of TAF-273 on phase 1 aminopyrine metabolism in adult male and female rat hepatocytes by using ten cellular stimulants/inhibitors. The study suggested that the effect of TAF-273 on hepatic phase 1 aminopyrine metabolism in adult male rats was probably mediated through the inhibition of tyrosine kinases and through the activation of G-protein, protein kinase G, protein kinase A in the cAMP pathway, calmodulin and protein kinase C. On the contrary, the extract affected adult female rat hepatocytes, only through the activation of G-protein, protein kinase G, protein kinase A in the cAMP pathway and protein kinase C. The effect of TAF-273 on aminopyrine metabolism in the presence of trifluoperazine, phorbol myristate acetate and genistein also exhibited significant difference (P<0.05) between male and female rats. The rate of aminopyrine metabolism was higher in male rats than in female rats and the effect of TAF-273 on aminopyrine metabolism at the molecular level was different in male and female rats on the activation of calmodulin, protein kinase C and tyrosine kinases.

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    • Search Google Scholar
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    • Search Google Scholar
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    • Search Google Scholar
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    • Search Google Scholar
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    • Search Google Scholar
  • Kanchanapoom, T., Kasai, R., Chumsri, P., Hiraga, Y. & Yamasaki, K. (2001): Canthin-6-one and β-carboline alkaloids from Eurycoma harmandiana. Phytochemistry, 56, 383–386.

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    • Search Google Scholar
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    • Search Google Scholar
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    • Search Google Scholar
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    • Search Google Scholar
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    • Search Google Scholar
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    • Search Google Scholar
  • Morita, H., Kishi, E., Takeya, K., Itokawa, H. & Iitaka, Y. (1993): Highly oxygenated quassinoids from Eurycoma longifolia. Phytocemistry, 33, 691–696.

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    • Search Google Scholar
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    Nash T. , 'The colorimetric estimation of formaldehyde by means of the Hantzsch Reaction ' (1953 ) 55 Biochem. J. : 416 -421.

    • Search Google Scholar
  • Oesch-Bartlomowicz, B. & Oesch, F. (2008): Phosphorylation of xenobiotic-metabolising cytochromes P450. Anal. Bioanal. Chem., 392, 1085–1092.

    Oesch F. , 'Phosphorylation of xenobiotic-metabolising cytochromes P450 ' (2008 ) 392 Anal. Bioanal. Chem. : 1085 -1092.

    • Search Google Scholar
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    Stevenson I.H. , 'Effect of age and sex on human drug metabolism ' (1971 ) 3 B. M. J. : 607 -609.

    • Search Google Scholar
  • Pelkonen, O., Turpeinen, M., Hakkola, J., Honkakoski, O., Hukkanen, J. & Raunio, H. (2008): Inhibition and induction of human cytochrome P450 enzymes: current status. Arch. Toxicol., 82, 667–715.

    Raunio H. , 'Inhibition and induction of human cytochrome P450 enzymes: current status ' (2008 ) 82 Arch. Toxicol. : 667 -715.

    • Search Google Scholar
  • Purwantiningsih, Hussin, A.H. & Chan, K.L. (2010): Phase I drug metabolism study of the standardised extract of Eurycoma longifolia (TAF-273) in rat hepatocytes. Int. J. Pharm. & Pharm. Sci., 2, 147–152.

    Chan K.L. , 'Phase I drug metabolism study of the standardised extract of Eurycoma longifolia (TAF-273) in rat hepatocytes ' (2010 ) 2 Int. J. Pharm. & Pharm. Sci. : 147 -152.

    • Search Google Scholar
  • Rees, D.D., Palmer, R.M.J., Schulz, R., Hodson, H.F. & Moncada, S. (1990): Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br. J. Pharmacol., 101, 746–752.

    Moncada S. , 'Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo ' (1990 ) 101 Br. J. Pharmacol. : 746 -752.

    • Search Google Scholar
  • Saxena, A., Tripathi, K.P., Roy, S., Khan, F. & Sharma, A. (2008): Pharmacovigilance: Effects of herbal components on human drugs interactions involving cytochrome P450. Bioinformation, 3, 198–204.

    Sharma A. , 'Pharmacovigilance: Effects of herbal components on human drugs interactions involving cytochrome P450 ' (2008 ) 3 Bioinformation : 198 -204.

    • Search Google Scholar
  • Simpson, C.S. & Morris, B.J. (1995): 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. Neuroscience, 68, 97–106.

    Morris B.J. , '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 ' (1995 ) 68 Neuroscience : 97 -106.

    • Search Google Scholar
  • Taher, Y.A. (1998): Study on traditional medicine-modern drug interaction and its molecular mechanism elucidation in rat liver. Unpublished Master’s Thesis, University Sains Malaysia, Penang, pp. 49–74.

    Taher Y.A. , '', in Study on traditional medicine-modern drug interaction and its molecular mechanism elucidation in rat liver , (1998 ) -.

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