RESUMO
Bufalin was a typical bioactive bufadienolide, existed in the traditional Chinese medicine Chan Su with the high content of 1-5%. The in vivo metabolites (1-5) of bufalin were prepared by various chromatographic techniques from the bile samples of SD rats, which were administrated with bufalin orally. Their structures were determined on the basis of the widely spectroscopic data, including HRESIMS, 1D-, and 2D NMR. And 1-3, 5 were new compounds. In the in vitro cytotoxicity assay, metabolites (1-5) showed weaker cytotoxic effects than bufalin against human cancer cell lines A549 and H1299, which indicated that the metabolism was a significant pathway for the detoxification of bufalin. Structures analyses indicated that metabolites 1-5 were hydroxylated derivatives of bufalin. This study suggested that Phase I metabolism catalyzed by CYP450 enzymes was one of the metabolic ways of bufalin, which may promote the excretion of bufalin.
Assuntos
Bufanolídeos/isolamento & purificação , Sistema Enzimático do Citocromo P-450/metabolismo , Animais , Bufanolídeos/química , Bufanolídeos/farmacologia , Humanos , Hidroxilação , Masculino , Medicina Tradicional Chinesa , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To study the effect of tanshinone microemulsion (Tan-M) on the cytotoxicity to human leukemia-cell-line (K562/ADM) and the reversion of MDR in vitro. METHOD: Microemulsion being supposed as the control group, MT method is adopted to test cytotoxicity and the reverse of MDR. RESULT: Obvious cytotoxicity to K562/ADM was observed for tan-M. Cell non-toxic dosage (growth quotiety > 95%) of Tan-M is 0.2 microg x mL(-1). Low toxic dosage (growth quotiety 85-90%) was 0.7 microg x mL(-1). Cell non-toxic dosage of was 0.7 microg x mL(-1) and low toxic dosage was 1.2 microg x mL(-1). Cell non-toxic dosage of Tan-M (0.2 microg x mL(-1)) significantly lowered the IC50 of K562/ADM by ADM (P < 0.01), and reversed MDR was 3.88 times. Low toxic dosage of Tan-M reversed MDR was 3.97 times. E-M (0.2 microg x mL(-1)) reversed MDR was 2.62 times. CONCLUSION: The result indicates that tanshinone microemulsion possesses cell-toxic effects on human leukemia cell-line and may reverse MDR of tumor cells.