In Vitro Effect of Mitragynine (a Major Alkaloid of Mitragyna Speciosa Korth) on Aminopyrine Metabolism in Rat Hepatocytes

Mitragyna speciosa Korth. is a member of the Rubiaceae family. More than 25 alkaloids have been isolated from Mitragyna speciosa. Mitragynine is the major alkaloid of this plant and is responsible for antinociceptive action. No single study is available about the effect of mitragynine on aminopyrine Ndemethylase activity in rat hepatocytes. Experiments were undertaken to evaluate the effect of mitragynine in different age groups (adult & old) of SpragueDawley (SD) male and female rat hepatocytes. In vitro this evaluation was assessed by different concentration of mitragynine (0.0025μM-250μM). Hepatocytes were prepared by collagenase perfusion technique. Aminopyrine N-demethylase activity was determined by measuring the quantity of formaldehyde formed. Results showed that a significant increase in aminopyrine N-demethylase activity was observed in the adult male, female and old female SD rat hepatocytes treated with 250μM mitragynine (p< 0.05). However, the old male rat did not show any significant change at any concentration of mitragynine. In conclusion this study indicates the induction of hepatic drug metabolizing enzymes by mitragynine is affected by the aging process in male but unaffected in female. INTRODUCTION: Natural products have served as a major source of drugs for centuries; about half of the drugs in use today are derived from them. Herbal medicine, quinine, theophylline, cyclosporine, penicillin G, morphine, digoxin, vincristine all are cornerstones of modern pharmaceutical care and they are herbal medicine. Herbal derived medicines are often administered orally and can attain moderate to high concentration in the liver. CYP3A4 are abundantly expressed in hepatocytes. The modulation of hepatic CYP3A4 by herbal medicines represents a potentially important mechanism by which the bioavailability of co-administered drugs can be modulated . Advances in detection of herbal drug component have increased the understanding of the relation between the specific component and effects. There is widespread concern on the harmful effects of herbal drugs consequently leading to a greater numbers of studies carried out on herbal drug interactions 2, 3, . A new herbal drug Mitragyna speciosa has strong abuse potential . It is found in tropical and subtropical regions of Asia, indigenous to Thailand, where is called kratom 6 and in Malaysia it is called ketum. It can also be found in Cambodia, East and West Africa and in India . In Malaysian folk medicine, the leaves are used to treat diarrhea, fever, asthma, antihypertensive, pain