Interactions of Orthosiphon stamineus and Morinda citrifolia with hepatic aminopyrine metabolism by CYP3A in rats

Herb-drug interaction studies have getting attention recently due to the increasingly use of herbal products worldwide. The porpose of the present study was to examine the in vitro effect of methanol leaf extract of Orthosiphon stamineus and Morinda citrifolia fruit juice extract on hepatic aminopyrine metabolism by CYP 3A in different age of normal and STZ-induced diabetic Sprague Dawley (SD) rats. Isolated rat hepatocytes were prepared using the collagenase perfusion technique. Aminopyrine was used as a probe substrate to determine the hepatic levels of CYP 3A by measuring the activity of N-demethylation of aminopyrine in rat hepatocytes according to the method described by Nash. Results obtained showed that aminopyrine N-demethylase activity measured from all diabetic rat hepatocytes was not affected by O. stamineus and M. citrifolia extract. A significant decrease in the aminopyrine N-demethylase activity was observed in the normal old male SD rat hepatocytes preincubated with 0.1 mg/kg (P<0.01) of methanol extract of O. stamineus when compared to the respective control group. M. citrifolia juice extract at 0.1 mg/ml (P<0.01) significantly increased aminopyrine N-demethylase activity in normal adult male SD rat hepatocytes as compared to the control group. For conclusion, both M. citrifolia and O. stamineus extract could affect the in vitro metabolism of aminopyrine by CYP3A in normal rat hepatocytes. No significant change in the hepatic aminopyrine metabolism was observed in the diabetic rats after incubating with different concentrations of M. citrifolia and O. stamineus extracts. The observed herb-drug interactions in the present study was age- and disease-dependent.