Cytotoxicity evaluation and metabolism of hepatotoxicity components of Euodiae Fructus in L02 cells.

Euodiae Fructus (EF), the dried unripe scented fruit of Euodia rutaecarpa (Juss.) Benth., was reported to show anti-hypertensive, antitumor, and anti-obesity effects. The main alkaloids of EF were reported as the reason for toxicity of EF by metabolic activation majority through CYP3A. Up till the present moment, the cytotoxicity mechanisms of EF have not yet to be fully clarified. For the purposes of this article, the influence of CYP3A inducer and inhibitor on cytotoxicity of EF and metabolism in L02 cells of five alkaloids related to toxicity of EF were evaluated. The results indicated that CYP3A inducer aggravated the toxicity and CYP3A inhibitor alleviated the toxicity. UPLC-Q-Exactive-MS was used for the identification of five alkaloids of EF in L02 cells. A total of 13 metabolites were detected in L02 cells. In general, five alkaloids were widely metabolized in L02 cells such as oxygenation, demethylation, dehydrogenation, and etc. In addition, oxygenation was the main metabolic pathway. It was inferred that the toxicity of EF was closely related to the CYP3A and the metabolic intermediate might be one of the reasons for the toxicity of EF. Hence, the choice of optimal dose might be critical to avoid the adverse reactions owing to combination of EF and CYP3A inducer.

Effect of Cinnamomum cassia on the Pharmacokinetics and Pharmacodynamics of Pioglitazone.

BACKGROUND: Millions of people today use herbs either as food or in the form of medicine along with other medications. Many of the herbs can interact with these medications, causing either potentially dangerous side effects or improved or reduced benefits from the medication. OBJECTIVE: The present study was performed to determine the influence of cinnamon, on the pharmacokinetics and pharmacodynamics of pioglitazone. METHOD: Studies were conducted in normal and alloxan induced diabetic rats and rabbits with oral administration of selected doses of pioglitazone, cinnamon and their combination. Blood samples were collected at regular intervals of time and were analysed for glucose by GOD/POD method and for pioglitazone by HPLC method respectively. Body weights were also measured every week. RESULTS: Significant differences were seen in pharmacokinetic parameters of pioglitazone like AUC, t1/2, Ke, Cl/F, Vd/F when given in combination with cinnamon in normal and diabetic rabbits. The combination of pioglitazone and cinnamon was found to reduce the glucose levels and body weights significantly than pioglitazone. The results indicating increased AUC of pioglitazone on pretreatment with cinnamon suggest an interaction indicating decreased metabolism of pioglitazone as a result of CYP 3A4 inhibition and thereby producing a potentiating effect. CONCLUSION: Cinnamon enhanced the bioavailability of pioglitazone by inhibiting the CYP3A4 enzyme. Hence, cinnamon might be beneficial when used in combination with pioglitazone in diabetic patients and an adjustment of dose of pioglitazone may be necessary.