Orthosiphon Stamineus Increases Metabolism of Aminopyrine in Female Rat Hepatocytes by Inhibiting Protein Kinase- A

Orthosiphon stamineus (Family: Lamiaceae) has becoming one of the popular medicinal plants in Malaysia due to its high beneficial effects in treating diabetes mellitus, hypertension and kidney stones. The present study was conducted to evaluate the mechanism of O. stamineus in affecting metabolism of aminopyrine in female rat hepatocytes via second messenger pathway. Liver perfusion was used to isolate hepatocytes from the healthy female Sprague Dawley (SD) rats. Isolated perfused rat hepatocytes were pretreated with several enzyme inhibitors/stimulant targeted on the protein kinases, phosphatase and phosphodiesterase. From the results obtained, only the activity of aminopyrine N-demethylase in female rat hepatocytes pre-treated with KT5720 showed significantly increased in the presence of 1 ng/ml (P<0.05) of O. stamineus extract. For conclusion, 1 ng/ml of O. stamineus extract increased the metabolism of aminopyrine in rat hepatocytes by inhibiting the protein kinaseA activity. INTRODUCTION: Orthosiphon stamineus belongs to the family of Lamiceae, is commonly used to treat diabetes mellitus, hypertension and gout problems in many Southeast Asia countries . In many European countries, O. stamineus is consumed as herbal tea to promote health due to its high antioxidant property . Recent researchers from Universiti Sains Malaysia had reported that rosmarinic acid is the main component in the methanol extract of O. stamineus with concentration ranging from 5.1 % to 29.9% of the total dry leaf weight. Concentrations of 3’-hydroxy-5, 6, 7, 4’-tetramethoxyflavone (TMF), eupatorin (EUP) and sinensetin (SEN) ranged from 0.05% to 0.69%, 0.34% to 3.37% and 0.22% to 1.76% respectively . Hence, it has a great potential to be commercialized due to its high medicinal value. The information with regard to the potential interaction of this plant with other modern drugs is still limited. Previously, we have reported on the in vitro effect of O. stamineus on the activity of aminopyrine N-demethylase in female rat hepatocytes . Precaution should be taken due to the possibility of causing herb-drug interaction if both are consumed at the same times. Herb-drug interaction can be defined as any alteration either in the pharmacokinetic or pharmacodynamic effect of the drug caused by concurrent treatment with herb and drug. Herb-drug interaction can be generally divided into pharmacokinetic and pharmacodynamic interactions . The liver is one of the hardest working organs in the body for xenobiotic and drug metabolism and detoxification process .