Effects of Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)on cytochrome P450 enzyme activities in rats

OBJECTIVE:To investigate the efficacy of Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)on cytochrome P450(CYP450)enzyme activities in rats.METHODS:A cocktail strategy was followed to evaluate the influence of Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)on the activities of CYP450 isoforms(CYP1A2,CYP3A4,CYP2E1,CYP2C19,CYP2C9,CYP2D6),which were determined by changes in the pharmacokinetic parameters of six probe drugs,theophylline,dapsone,chlorzoxazone,omeprazole,tolbutamide and dextromethorphan.Study groups included,Control group(CG),Tianma(Rhizoma Gastrodiae)group(TM),Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)group(GT)and Tianma Gouteng(Gastrodia Uncaria)group(TMGT).RESULTS:No significant differences between Tianma(Rhizoma Gastrodiae)and control groups were found.Compared with the control group,in the Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)group both the AUC and t1/2 of dapsone and tolbutamide were reduced,whereas the CL(clearance rate)of dapsone and tolbutamide were increased.Compared with the control group,in the Tianma Gouteng group,the AUC and t1/2 of dapsone and tolbutamide were reduced,the CL of dapsone and tolbutamide were increased,and the AUC and t1/2 of chlorzoxazone were increased and the CL of chlorzoxazone was reduced.CONCLUSION:Tianma(Rhizoma Gastrodiae)has no significant effect on the six CYP450 subtypes.The activities of CYP3A4 and CYP2C9 were increased by Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis).The activities of CYP3A4 and CYP2C9 were increased,whereas the activity of CYP32E1 was reduced by combined Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis).

UFLC‑PDA‑MS/MS Profling of Seven Uncaria Species Integrated with Melatonin/5‑Hydroxytryptamine Receptors Agonistic Assay

Uncariae Ramulus Cum Uncis(Gou-Teng),the dried hook-bearing stems of several Uncaria plants(Rubiaceae),is a wellknown herbal medicine in China.The clinical application of Gou-Teng is bewildered for the morphological and chemical similarity between diferent species.In order to discern their chemical and biological diference,an ultra-fast liquid chromatography equipped with ion trap time-of-fight mass spectrometry(UFLC-IT/TOF-MS)combining with melatonin(MT1 and MT2)and 5-hydroxytryptamine(5-HT1A and 5-HT2C)receptors agonistic assay in vitro was conducted on seven Uncaria species.As a result,57 compounds including 35 indole alkaloids,ten favonoids,fve triterpenoids,fve chlorogenic analogues,and two other compounds were characterized based on their MS/MS patterns and UV absorptions.Specifcally,cadambine-type and corynanthein-type alkaloids were exclusively present in U.rhynchophylla and U.scandens,whereas corynoxine-type alkaloids were commonly detected in all the seven Uncaria plants.Three Uncaria species,U.rhynchophylla,U.macrophylla,and U.yunnanensis showed obviously agnostic activity on four neurotransmitter receptors(MT1,MT2,5-HT1A,and 5-HT_(2C)).This frst-time UFLCMS-IT-TOF analyses integrated with biological assay on seven Uncaria plants will provide scientifc viewpoints for the clinical application of Gou-Teng.