RESUMEN
To date, pharmacokinetics of maslinic (MA) and oleanolic (OA) acids, at normal dietary intakes in humans, have not been evaluated, and data concerning their bioactive effects are scarce. We assessed MA and OA pharmacokinetics after ingestion of olive oils (OOs) with high and low triterpenic acid contents, and specifically the effect of triterpenes on endothelial function. We performed a double-blind, dose-response, randomized, cross-over nutritional intervention in healthy adults, and observed that MA and OA increased in biological fluids in a dose-dependent manner. MA bioavailability was greater than that of OA, and consumption of pentacyclic triterpenes was associated with improved endothelial function. To the best of our knowledge, this is the first time MA pharmacokinetics, and effects on endothelial function in vivo, have been reported in humans.
Asunto(s)
Ácido Oleanólico/farmacocinética , Aceite de Oliva/metabolismo , Triterpenos/farmacocinética , Adulto , Presión Sanguínea , Estudios Cruzados , Método Doble Ciego , Endotelio/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ácido Oleanólico/sangre , Ácido Oleanólico/orina , Aceite de Oliva/química , Triterpenos/sangre , Triterpenos/orina , Adulto JovenRESUMEN
OBJECTIVE: To determinate triptolide and wilforlide A in biological samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method and to verify the method. METHODS: After 0.4 mL blood, urine or 0.4 g hepatic tissues with internal standard were extracted by ethyl acetate, they were separated on a Allure PFP Propyl (100 mm x 2.1 mm, 5 µm) with a mobile phase of methanol-20 mmol/L ammonium acetate using gradient elution. For mass spectrometric detection, electrospray ionization (ESIâº) in positive mode was elected and the data was collected using multiple-reaction monitoring (MRM). RESULTS: The linearity was good (r > 0.995 0) and the limit of detection was 2 ng/mL or 2 ng/g for triptolide and wilforlide A. The recovery was 61.08%-102.98%. The intra-day and inter-day precision was less than 12.58% for each biological sample, and the accuracy was 90.61%-105.80%. CONCLUSION: This method is simple, convenient and good selective, and could be applied to analysis of triptolide and wilforlide A in different biological samples. And the method may provide technical support for forensic medicine identification, clinical diagnosis and treatment of tripterygium wilfordii Hook. f. poisoning.
Asunto(s)
Cromatografía Líquida de Alta Presión , Diterpenos/sangre , Diterpenos/orina , Ácido Oleanólico/análogos & derivados , Fenantrenos/sangre , Fenantrenos/orina , Espectrometría de Masas en Tándem , Compuestos Epoxi/sangre , Compuestos Epoxi/orina , Humanos , Ácido Oleanólico/sangre , Ácido Oleanólico/orina , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE@#To determinate triptolide and wilforlide A in biological samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method and to verify the method.@*METHODS@#After 0.4 mL blood, urine or 0.4 g hepatic tissues with internal standard were extracted by ethyl acetate, they were separated on a Allure PFP Propyl (100 mm x 2.1 mm, 5 µm) with a mobile phase of methanol-20 mmol/L ammonium acetate using gradient elution. For mass spectrometric detection, electrospray ionization (ESI⁺) in positive mode was elected and the data was collected using multiple-reaction monitoring (MRM).@*RESULTS@#The linearity was good (r > 0.995 0) and the limit of detection was 2 ng/mL or 2 ng/g for triptolide and wilforlide A. The recovery was 61.08%-102.98%. The intra-day and inter-day precision was less than 12.58% for each biological sample, and the accuracy was 90.61%-105.80%.@*CONCLUSION@#This method is simple, convenient and good selective, and could be applied to analysis of triptolide and wilforlide A in different biological samples. And the method may provide technical support for forensic medicine identification, clinical diagnosis and treatment of tripterygium wilfordii Hook. f. poisoning.
Asunto(s)
Humanos , Cromatografía Líquida de Alta Presión , Diterpenos/orina , Compuestos Epoxi/orina , Ácido Oleanólico/orina , Fenantrenos/orina , Sensibilidad y Especificidad , Espectrometría de Masas en TándemRESUMEN
The main objective of the present study was to completely characterize the metabolites of the triterpenoid saikosaponin a (SSa) in rats. To this aim, we compared the metabolites in plasma, bile, urine, and feces samples following oral and i.v. routes of administration using liquid chromatography-diode array detector coupled with hybrid ion trap-time-of-flight mass spectrometry. As a result, besides 2 known metabolites, prosaikogenin f and saikogenin f, 15 new metabolites were detected in all. It was found that SSa is metabolized mainly in phase I manner, i.e., hydration and monooxidation on the aglycone moiety and hydrolysis of the ß-glucosidic bond in the liver, and sequential hydrolysis of ß-glucosidic and ß-fucosidic bonds followed by dehydrogenation, hydroxylation, carboxylation, and combinations of these steps on the aglycone moiety in the intestinal tract. Both the renal and biliary routes were observed for the excretion of SSa and its metabolites. Further, a clear metabolic profile in rats was proposed in detail according to the results from the in vivo animal experiment after different routes of administration. Our results update the preclinical metabolism and disposition data on SSa, which is not only helpful for the future human metabolic study of this compound but also provides basic information for better understanding of the efficacy and safety of prescriptions containing saikosaponins.
Asunto(s)
Medicamentos Herbarios Chinos/farmacocinética , Intestinos/enzimología , Hígado/enzimología , Ácido Oleanólico/análogos & derivados , Saponinas/farmacocinética , Administración Oral , Animales , Bilis/metabolismo , Biotransformación , Cromatografía Liquida , Medicamentos Herbarios Chinos/administración & dosificación , Heces/química , Hidrólisis , Inyecciones Intravenosas , Masculino , Estructura Molecular , Ácido Oleanólico/administración & dosificación , Ácido Oleanólico/sangre , Ácido Oleanólico/farmacocinética , Ácido Oleanólico/orina , Oxidación-Reducción , Ratas , Ratas Sprague-Dawley , Saponinas/administración & dosificación , Saponinas/sangre , Saponinas/orina , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
A rapid, sensitive, and specific method by high-performance liquid chromatography (HPLC) coupled to diode-array detection (DAD) and tandem mass spectrometry (MS) techniques was developed for the identification of absorbed constituents and their metabolites in rats after the oral administration of a Chai-Huang decoction (CHD), which consists of Bupleurum chinense and Scutellaria baicalensis in the proportion 1 : 1 (w/w). By comparing their retention times and MS data with those of authentic compounds and published data, a total of 14 compounds were identified in the CHD samples. In addition, eleven and seven compounds were characterized in the urine and serum samples of the rats, respectively. The results indicated that the main absorbed constituents were chrysin-6-C-arabinosyl-8-C-glucoside, chrysin-6-C-glucosyl-8-C-arabinoside, baicalin, wogonin-5-O-glucoside, oroxylin A-7-O-glucuronide, wogonoside, saikosaponin A, saikosaponin C, saikosaponin D, baicalein, and wogonin. These compounds might be responsible for the curative effects of the CHD. The findings demonstrated that the proposed method could be used to rapidly and simultaneously analyze and screen the multiple absorbed bioactive constituents in a formula of traditional Chinese medicines (TCM). This is very important not only for the pharmaceutical discovery process and the quality control of crude drugs but also to explain the mechanisms of action of TCM.