RESUMO
INTRODUCTION: It has been reported that the phenolic metabolite 3'-methoxycinnamic acid-4'-sulfate generated from 5-O-caffeoylquinic acid may have potential benefits in human health. However, the variation in 3'- and 4'-methylation of 3',4'-dihydroxycinnamic acid and its impact on the yield of this sulfate metabolite is unclear and has been poorly studied. METHODS AND RESULTS: To address this aim, the excreted 3'-methoxy and 4'-methoxy metabolites in urine samples (24-h) are determined in 14 volunteers after an acute intake of 80 g of red-fleshed apple (RFA) or white-fleshed apple (WFA). These methoxy metabolites are also determined in the same volunteers in a second acute intake after a 6-week sustained consumption of the same products. CONCLUSION: Seven 3'-methoxy and seven 4'-methoxy metabolites are determined, i.e., the free cinnamic and corresponding phenylpropanoic acid, plus their sulfate, glucuronide, and glycine conjugates. In only six volunteers, five females and one male, is 4'-methylation preferred over 3'-methylation, but it is observed that an individual's 3'- : 4'-methylation ratio can change over time, and that the yield of 3'-methoxycinnamic acid-4'-sulfate is extremely variable, ranging from undetectable to 71% of the total C6 -C3 metabolites excreted, and any benefit accruing from this metabolite will not necessarily be available to all consumers.
Assuntos
Malus , Ácido Quínico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Malus/química , Metilação , Período Pós-Prandial , Ácido Quínico/análogos & derivados , Ácido Quínico/metabolismo , Ácido Quínico/farmacocinéticaRESUMO
The current study aimed to evaluate how the harvest time affects the phenolic composition in Burdock root flours (BRF) and how these phenolics are influenced by the gastro-intestinal digestive environment. Burdock roots were harvested in 2020 in Jiangsu Province in June (B1), July (B2) and August (B3). The main phenolic, 5-O-caffeoylquinic acid (5-CQA) decreased after in vitro digestion from 1.14 to 0.22 mg/g (B1 < B2 < B3). Total phenolic content of BRF was 61% lower after in vitro digestion whereas 5-CQA bioaccessibility remained at about 60%. Twelve other phenolic compounds were tentatively identified after in vitro digestion. An average reduction in antioxidant capacity of 27% and 10% was observed for DPPH and ABTS, respectively. In conclusion, data demonstrated that phenolic composition, bioaccessibility and antioxidant capacity of Burdock roots harvested at different times were subject to the influence of in vitro gastrointestinal digestion.
Assuntos
Antioxidantes/análise , Arctium/química , Fenóis/análise , Fenóis/farmacocinética , Antioxidantes/química , Antioxidantes/farmacocinética , Arctium/metabolismo , Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/análise , Ácido Clorogênico/química , Ácido Clorogênico/farmacocinética , Digestão , Farinha/análise , Fenóis/química , Raízes de Plantas/química , Ácido Quínico/análogos & derivados , Ácido Quínico/análise , Ácido Quínico/química , Ácido Quínico/farmacocinética , Fatores de TempoRESUMO
Chlorogenic acid (5-CQA), neochlorogenic acid (3-CQA), and cryptochlorogenic acid (4-CQA), usually simultaneously exist in many traditional Chinese medicines (TCMs). However, insufficient attentions have been paid to the comparative metabolism study on these three isomeric constituents with similar effects on anti-inflammation until now. In this study, a novel strategy was established to perform comparative analysis of their metabolic fates in rats and elucidate the pharmacological mechanism of anti-inflammation. Firstly, diagnostic product ions (DPIs) deduced from the representative reference standards were adopted to rapidly screen and characterize the metabolites in rat plasma, urine and faeces using UHPLC-Q-TOF MS. Subsequently, Network pharmacology was utilized to elucidate their anti-inflammatory mechanism. Consequently, a total of 73 metabolites were detected and characterized, including 50, 47 and 43 metabolites for 5-CQA, 4-CQA and 3-CQA, orderly. Moreover, the network pharmacology study indicated that these three isomeric constituents and their major metabolites with similar in vivo metabolic pathways exerted anti-inflammatory effects through co-owned 20 biological processes, which involved 10 major signal pathways and 159 potential targets. Our study shed light on the similarities and differences of the metabolic profiling and anti-inflammatory activity among these three isomeric constituents and set an example for the further researches on the active mechanism of isomeric constituents existing in TCMs based on comparative metabolism study.
Assuntos
Ácido Clorogênico/análogos & derivados , Medicamentos de Ervas Chinesas , Ácido Quínico/análogos & derivados , Animais , Ácido Clorogênico/farmacocinética , Ácido Clorogênico/farmacologia , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Ácido Quínico/farmacocinética , Ácido Quínico/farmacologia , RatosRESUMO
Eggplant is an important component of the Mediterranean Diet, which becomes edible after cooking. This study determined the fate of dark purple eggplant phenolic compounds after baking, boiling, frying, grilling and digestion. Thirty-seven phenolic compounds were identified and quantified in raw eggplant. Frying determined a 74% increase in total hydroxycinnamic acids whereas a decrease was observed after boiling (27%), grilling (51%), and baking (60%). After digestion, 45%, 33% and 22% of total phenolic compounds resulted bioaccessible in baked, grilled and fried dark purple eggplant. Fried eggplant displayed the highest amount of phenolic compounds (751.46 mg/100 g) after digestion. The cooking methods differently affected the release of individual phenolic compounds. Baking and grilling resulted in higher amount of bioaccessible caffeoylquinic acids whereas frying in di-caffeoylquinic acids and hydroxycinnamic acid-amides. A careful design of the cooking method may be pivotal to modulate the release of specific phenolic compounds.
Assuntos
Culinária/métodos , Fenóis/química , Solanum melongena/química , Disponibilidade Biológica , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacocinéticaRESUMO
A simple and specific, rapid resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for determination of chlorogenic acid in human plasma using neochlorogenic acid as the internal standard. Plasma samples were precipitated with methanol and separated on a Zorbax C18 column (50â¯×â¯2.1â¯mm, i.d. 1.8⯵m) at a flow rate of 0.4â¯mL/min using a gradient mobile phase of methanol-water containing 0.1% formic acid (v/v). The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring in negative ESI mode. The method was fully validated over the concentration range of 10-2000â¯ng/mL. The indicators of inter- and intra-day precision (RSD%) were all within 10.7%, and the accuracy (RE%) was ranged from -3.0% to 10.6%. Moreover, we evaluated this bioanalytical method by re-analysis of incurred samples as an additional measure of assay reproducibility. This method was successfully applied to pharmacokinetic study of CGA in Chinese subjects with advanced solid tumor after intramuscular injection administration of Chlorogenic acid for injection (CAFI).
Assuntos
Anticarcinógenos/sangue , Ácido Clorogênico/análogos & derivados , Ensaios de Triagem em Larga Escala/métodos , Neoplasias/tratamento farmacológico , Ácido Quínico/análogos & derivados , Espectrometria de Massas em Tandem/métodos , Anticarcinógenos/administração & dosagem , Anticarcinógenos/farmacocinética , Área Sob a Curva , China , Ácido Clorogênico/administração & dosagem , Ácido Clorogênico/sangue , Ácido Clorogênico/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Relação Dose-Resposta a Droga , Esquema de Medicação , Estabilidade de Medicamentos , Humanos , Injeções Intramusculares , Neoplasias/sangue , Ácido Quínico/administração & dosagem , Ácido Quínico/sangue , Ácido Quínico/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Multicompound determination for the quality control of traditional Chinese medicine (TCM) may often be inadequate, since these compounds may not be associated with, or fully represent, the clinical effects of TCM. Moreover, the individual contributions of each constituent to the pharmacological effect are often not considered. In China, Porana sinensis is widely used as a substitute for Erycibe sources to treat joint pain and rheumatoid arthritis. The existing quality control methods for P. sinensis neither consider the individual contributions of various compounds nor control the actual quality associated with different clinical efficacies. In the present study, a novel efficacy-oriented approach, named the effect-constituent index (ECI), was established for P. sinensis. Analyses of the spectrum-effect relationship and components in rat plasma were conducted to systematically and scientifically select quality markers. Quantitative analysis of multicomponents via a single marker method was introduced to enhance the practical application value of the established ECI. The established ECI shows a good ability to distinguish and predict the bioeffect-based quality of P. sinensis. The present study also provides a reference for the establishment and application of ECI as a quality control method for TCMs.
Assuntos
Convolvulaceae/química , Medicamentos de Ervas Chinesas , Animais , Ácido Clorogênico/sangue , Ácido Clorogênico/química , Ácido Clorogênico/farmacocinética , Cromatografia Líquida de Alta Pressão , Cumarínicos/sangue , Cumarínicos/química , Cumarínicos/farmacocinética , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/normas , Glucosídeos/sangue , Glucosídeos/química , Glucosídeos/farmacocinética , Modelos Lineares , Medicina Tradicional Chinesa , Controle de Qualidade , Ácido Quínico/análogos & derivados , Ácido Quínico/sangue , Ácido Quínico/química , Ácido Quínico/farmacocinética , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos TestesRESUMO
SCOPE: Quinic acid in its free form is broadly abundant in plants, and can accumulate in copious amounts in coffee, tea, and certain fruits. However, it has been mostly studied as chlorogenic acid, an ester of caffeic and quinic acids. When chlorogenic acid reaches the colon, it is hydrolyzed by microbial esterases releasing caffeic and quinic acids. While biotransformation of chlorogenic and caffeic acids have been elucidated by in vitro and in vivo studies, the gut metabolism of quinic acid has been so far overlooked. METHODS AND RESULTS: [U-13 C]-Quinic acid is submitted to a colonic model using human fecal microbiota for assessing its metabolic fate. The metabolite profiles formed along microbial biotransformation are monitored by a combined metabolomics approach, using both 2D GC- and ultra-HPLC-MS. Six metabolic intermediates are identified by incorporation of isotopic label. CONCLUSION: Two parallel degradation pathways could be proposed: (1) an oxidative route, leading to aromatization and accumulation of protocatechuic acid, and a (2) reductive route, including dehydroxylation to cyclohexane carboxylic acid. Elucidating the biotransformation of food bioactives by the gut microbiota is of relevance for understanding nutrition, interindividual variability and potential effects on human metabolism.
Assuntos
Microbioma Gastrointestinal/fisiologia , Ácido Quínico/farmacocinética , Isótopos de Carbono/farmacocinética , Ácido Clorogênico/metabolismo , Ácido Clorogênico/farmacocinética , Fezes/microbiologia , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Ácido Quínico/metabolismoRESUMO
Acute lung injury (ALI) is a severe inflammatory disease with high mortality rates. Di-caffeoylquinic acids (DCQAs), the bioactive components of reduning injection (RDN), may play important roles in the protective effect on acute lung injury (ALI). A selective and rapid ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method has been developed and validated for the simultaneous determination of 3,4-, 3,5- and 4,5-DCQA in rat plasma. The DCQAs were extracted by liquid-liquid extraction with ethyl acetate-isopropyl alcohol (7:3, v/v). Chromatographic separation was accomplished on a C18 column using gradient elution. Detection was performed in the multiple reaction monitoring (MRM) mode. The lower limits of quantification were all 2.0ng/mL for the three analytes. Intra-day and inter-day precision were less than 15% and accuracy ranged from -13.8% to 10.0%, and the mean extraction recoveries of analytes from rat plasma were all more than 72.9%. Meanwhile, this method had been successfully applied to compare the pharmacokinetics of the three DCQAs in normal and ALI model rat after RDN was given intravenously administration. The pharmacokinetic parameters of the 3,4-, 3,5- and 4,5- DCQA were remarkably different from those in normal rats. It might result from the effects of the pathological status of ALI. This study presented a meaningful basis for the clinical applications of RDN when used in the treatment of ALI.
Assuntos
Lesão Pulmonar Aguda/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Ácido Quínico/análogos & derivados , Espectrometria de Massas em Tandem/métodos , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacocinética , Limite de Detecção , Modelos Lineares , Masculino , Ácido Quínico/sangue , Ácido Quínico/química , Ácido Quínico/farmacocinética , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos TestesRESUMO
Wine-processing, which is sauteing with rice wine, will change the inclination and direction of herbs' actions. After being wine-processed, the effects of nourishing liver and kidney of Dipsacus asper will be strengthened. However, the underlying mechanism remains elusive. The following study is to establish and validate an UHPLC-MS/MS approach to determine six bioactive constituents in tissue samples, including loganin, loganic acid, chlorogenic acid, 3,5-dicaffeoylquinic acid, 4-caffeoylquinic acid and asperosaponin VI and apply the approach to a comparative tissue distribution study of raw and wine-processed Dipsacus asper in rats. A Shimadzu UHPLC system coupled with triple quadrupole mass spectrometer was employed for analysis of the six analytes using multiple reaction monitoring (MRM) mode. A one-step protein precipitation by methanol was employed to extract the six analytes from tissues. Chloramphenicol and glycyrrhetinic acid were selected as internal standards. The proposed approach was fully validated in terms of linearity, sensitivity, precision, repeatability as well as recovery. Our results revealed that all of the calibration curves displayed good linear regression (r2>0.9991). Intra- and inter-assay variability for all analytes ranged from -4.62 to 4.93% and from -4.98 to 4.92%, respectively. The recovery rates for each analytes were determined to be 88.3-100.1%. All the samples showed satisfactory precision and accuracy after various stability tests, including storage at 25°C for 4h, -80°C for 30days, three-freeze-thaw cycles, and 4°C for 24h. Tissue pharmacokinetic parameters including AUC0-t, t1/2, Tmax and Cmax were calculated. Collectively, the parameters of Cmax and AUC0-t of the six analytes in wine-processed group were remarkably elevated (p<0.05) in the rat liver and kidney as compared with those of the raw group. But in the rat heart and spleen, the Cmax and AUC0-t of asperosaponin VI was decreased as compared with those of the raw group. The accumulation of bioactive constituents in liver and kidney tissues after wine-processing will contribute to the enhancement of liver and kidney nourishing effects.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Dipsacaceae/química , Extratos Vegetais/farmacocinética , Espectrometria de Massas em Tandem/métodos , Animais , Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/análise , Ácido Clorogênico/farmacocinética , Iridoides/análise , Iridoides/farmacocinética , Masculino , Extratos Vegetais/análise , Plantas Medicinais/química , Ácido Quínico/análogos & derivados , Ácido Quínico/análise , Ácido Quínico/farmacocinética , Ratos , Ratos Sprague-Dawley , Saponinas/análise , Saponinas/farmacocinética , Distribuição Tecidual , Vinho/análiseRESUMO
PURPOSE: Yerba maté is widely consumed in South America as different beverages, such as maté tea (roasted leaves) and chimarrão (green dried leaves), and linked to health benefits, mainly attributed to chlorogenic acids (CGAs). Health effects of CGAs depend on their bioavailability, but such data are scarce. The aim of this study was to investigate the distribution of CGAs and metabolites in tissues, hepatic and plasmatic kinetic profile and urinary excretion after ingestion of maté tea or 5-caffeoylquinic acid (5-CQA). METHODS: Wistar rats ingested maté tea (MT) or 5-CQA (ST) and were killed after 1.5 h for tissue distribution analysis (pilot study) or at 0.5, 1, 2, 4 and 8 h for liver and plasma kinetics (main experiment). Urine was collected in metabolic cages. Biological samples were analyzed by UPLC-DAD-MS with and without incubation with ß-glucuronidase and sulfatase. RESULTS: CGAs and metabolites were detected in all tissues. Caffeic acid was the main compound in plasma up to 2 h after ingestion of maté tea, while 5-CQA predominated in ST group. Concentration of microbial metabolites increased 4 h after gavage and reached higher amounts in MT plasma and liver, when compared to ST group. Approximately 4.0 % of compounds ingested by MT and 3.3 % by ST were recovered in urine up to 8 h after the gavage. CONCLUSION: The study confirms that not only absorption, but also metabolization of CGAs begins in stomach. There were differences in compounds formed from maté tea or isolated 5-CQA, showing that CGAs profile in food may influence qualitatively and quantitatively the metabolites formed in the body.
Assuntos
Ácido Clorogênico/farmacocinética , Ilex paraguariensis/química , Ácido Quínico/análogos & derivados , Chás de Ervas , Animais , Disponibilidade Biológica , Ácidos Cafeicos/sangue , Ácido Clorogênico/administração & dosagem , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacocinética , Folhas de Planta/química , Polifenóis/administração & dosagem , Polifenóis/farmacocinética , Polifenóis/urina , Ácido Quínico/administração & dosagem , Ácido Quínico/farmacocinética , Ratos , Ratos Wistar , América do SulRESUMO
A rapid and sensitive assay based on ultra-high performance liquid chromatography with electrospray ionization tandem mass spectrometry was established and validated for the simultaneous determination of cichoric acid, chlorogenic acid, quinic acid, and caffeic acid in rat plasma after oral administration of Echinacea purpurea extract using butylparaben as the internal standard. Samples were pretreated by liquid-liquid extraction with ethyl acetate. The separations for analytes were performed on an ACQUITY UPLC HSS C18 column (1.8 µm 2.1 × 100 mm) using a gradient elution program with acetonitrile/10 mM ammonium acetate (pH 5.6) at a flow rate of 0.3 mL/min. The analytes were detected in multiple reaction monitoring mode with negative electrospray ionization. The lower limit of quantification of each analyte was not higher than 10.85 ng/mL. The relative standard deviation of the intraday and interday precisions was less than 14.69%. The relative errors of accuracies were in the range of -13.80 to 14.91%. The mean recoveries for extraction recovery and matrix effect were higher than 80.79 and 89.98%, respectively. The method validation results demonstrated that the proposed method was sensitive, specific, and reliable, which was successfully applied to the pharmacokinetic study of four components after oral administration of Echinacea purpurea extract.
Assuntos
Ácidos Cafeicos/farmacocinética , Ácido Clorogênico/farmacocinética , Echinacea/química , Extratos Vegetais/química , Ácido Quínico/farmacocinética , Succinatos/farmacocinética , Administração Oral , Animais , Ácidos Cafeicos/sangue , Ácidos Cafeicos/química , Ácido Clorogênico/sangue , Ácido Clorogênico/química , Cromatografia Líquida de Alta Pressão , Masculino , Conformação Molecular , Extratos Vegetais/administração & dosagem , Ácido Quínico/sangue , Ácido Quínico/química , Ratos , Ratos Sprague-Dawley , Succinatos/sangue , Succinatos/química , Espectrometria de Massas em TandemRESUMO
Artichoke is a rich source of health promoting compounds such as polyphenols, important for their pharmaceutical and nutritional properties. In this study, the potential for bioavailability of the artichoke polyphenols was estimated by using both in vitro digestion and Caco-2 human intestinal cell models. In vitro digestive recoveries (bio-accessibility) were found to be 55.8% for total artichoke phenolics and in particular, 70.0% for chlorogenic acid, 41.3% for 3,5-O-dicaffeoylquinic acid, and 50.3% for 1,5-O-dicaffeoylquinic acid, highlighting potential sensitivity of these compounds to gastric and small intestinal digestive conditions. Uptake of artichoke polyphenols was rapid with peak accumulation occurring after 30 min with an efficiency of 0.16%, according to the poor uptake of dietary polyphenols. Some compounds, such as coumaric acid, caffeic acid and caffeic acid derivatives, were also detected in the basolateral side assuming extra and intracellular esterase activities on chlorogenic acid. Only apigenin-7-O-glucoside was transported through the Caco-2 monolayer demonstrating its bioavailability to the extent of 1.15% at 60 min. In addition, permeability coefficient (Papp = 2.29 × 10(-5) cm s(-1)), involving apical to basolateral transport of apigenin 7-O-glucoside, was calculated to facilitate estimation of transport through the Caco-2 monolayer. Finally, the mono and dicaffeoylquinic acids present in artichoke heads exert an antioxidant activity on the human low density lipoprotein system correlated to their chemical structure. In conclusion, the utilized in vitro models, although not fully responding to the morphological and physiological features of human in vivo conditions, could be a useful tool for investigating mechanistic effects of polyphenols released from the food matrix.
Assuntos
Cynara scolymus/química , Intestinos/citologia , Polifenóis/farmacocinética , Antioxidantes/farmacocinética , Disponibilidade Biológica , Células CACO-2 , Ácidos Cafeicos/farmacocinética , Ácido Clorogênico/farmacocinética , Ácidos Cumáricos/farmacocinética , Trato Gastrointestinal/citologia , Trato Gastrointestinal/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Metabolismo dos Lipídeos , Extratos Vegetais/farmacocinética , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacocinéticaRESUMO
Ainsliaea fragrans Champ, as a well-known herb in Traditional Chinese Medicine, was often used in the treatment of gynecological diseases. Caffeoylquinic acids (CQAs) were the bioactive constituents of this plant medicine which primarily contains mono-CQAs (MCQA) and di-CQAs (DCQA). The biosynthesis showed that MCQAs were the precursor of DCQAs. Recent literatures manifested some particular features of DCQAs, different from MCQAs. Therefore it is apparent that a complete and scientific assessment of DCQAs and MCQAs should include not only the DCQAs' pharmacokinetics and distribution but also its degradation products. So an efficient, sensitive rapid resolution liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of the active ingredients in rat plasma and different tissues had been developed and validated. Mass spectrometric detection was performed by selected reaction monitoring mode (MRM) via an electrospray ionization source operating in negative ionization mode. The method was validated in plasma and tissue samples, which showed good linearity over a wide concentration range (r(2)>0.99), and obtained lower limit of quantification (LLOQ) was 2.34 ng·mL(-1) for the analytes in biological samples. The intra- and inter-day assay variability was less than 15%, and the accuracy was between -8.8% and 5.7%. This study provided the pharmacokinetic profiles and the tissue regional distribution of MCQAs, DCQAs and caffeic acid. The results indicated that the DCQAs isomers were absorbed quickly after oral administration and degradation products MCQAs were mostly found in tissues, not in plasma. Besides, 1,5-DCQA was the prior configuration for the isomerization phenomenon. The small intestine was the main absorption site for DCQAs. Interestingly, the content of the DCQA and MCQA isomers was all high in the ovary and uterus, and some could pass through the barrier between the blood and brain obviously.
Assuntos
Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/farmacocinética , Ácido Quínico/análogos & derivados , Espectrometria de Massas em Tandem , Animais , Feminino , Isomerismo , Estrutura Molecular , Ácido Quínico/farmacocinética , Ratos Wistar , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição TecidualRESUMO
Single servings of coffee beverage containing low (412 µmol), medium (635 µmol) and high (795 µmol) amounts of chlorogenic acids were administered to eleven healthy volunteers in a double-blind randomised controlled trial. Analysis of plasma and urine collected for 24 h revealed the presence of 12 metabolites in plasma and 16 metabolites in urine, principally in the form of sulphates, and to a lesser extent glucuronides of caffeic, ferulic, dihydrocaffeic and dihydroferulic acids, as well as intact feruloylquinic and caffeoylquinic acids, and sulphated caffeoylquinic acid lactones. Median values of peak plasma concentrations after increasing doses of chlorogenic acids were 1088, 1526 and 1352 nM. In urine the median amounts of metabolites excreted after 24 h following consumption of the three coffees were 101, 160 and 125 µmol, accounting for 24%, 25% and 16% of the doses ingested. Peak plasma concentration and urinary excretion values showed trends towards a reduced bioavailability of chlorogenic acids associated with the highest dose ingested, when expressed as percentages of intake. Potential biomarkers of coffee intake were identified as feruloylquinic acids and sulphated caffeoylquinic acid lactones in plasma and urine with positive moderate to strong coefficients of determination for peak plasma concentrations (0.60-0.81) and amounts excreted in urine (0.36-0.73) (P < 0.05).
Assuntos
Ácido Clorogênico/farmacocinética , Café/química , Adulto , Disponibilidade Biológica , Ácidos Cafeicos/farmacocinética , Ácido Clorogênico/administração & dosagem , Cromatografia Líquida de Alta Pressão , Ácidos Cumáricos/farmacocinética , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Glucuronídeos/farmacocinética , Voluntários Saudáveis , Humanos , Masculino , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacocinética , Adulto JovemRESUMO
BACKGROUND: Polyphenols are thought to play important roles in human nutrition and health but these health effects are dependent on their bioavailability. This study is one of a series with the aim of determining possible effects of food matrices on caffeoylquinic acid (CQA) bioavailability using ileostomy volunteers. METHODS: After a CQA-free diet, ileostomists consumed coffee (746 µmol total CQA), and CQAs in excreted ileal fluid were subsequently identified and quantified with HPLC-diode array detection and HPLC-ESI-MS/MS. In our previous studies, other food sources such as cloudy apple juice (CAJ) (358 µmol CQA) and apple smoothie (AS) (335 µmol CQA) were investigated with the same model. RESULTS: Interesterification of CQA from both apple matrices was observed during gastrointestinal passage, whereas CQA consumed in coffee was not influenced by interesterification reactions. In total, 74.3, 22.4, and 23.8 % of the CQA from CAJ, AS, and coffee, respectively, were absorbed or degraded. CONCLUSION: Our results show that variations in food matrices and variations in phenolic composition have a major influence on intestinal bioavailability and interesterification of the investigated subclass of polyphenols, the CQAs.
Assuntos
Ileostomia , Absorção Intestinal , Ácido Quínico/análogos & derivados , Adulto , Bebidas , Disponibilidade Biológica , Índice de Massa Corporal , Peso Corporal , Cromatografia Líquida de Alta Pressão , Café/química , Feminino , Voluntários Saudáveis , Humanos , Mucosa Intestinal/metabolismo , Malus/química , Polifenóis/química , Ácido Quínico/administração & dosagem , Ácido Quínico/farmacocinéticaRESUMO
Qingkailing (QKL) injection, a modified modern Chinese medicine preparation, is widely used in the clinic for its significant antipyretic and anti-inflammatory effects, but its serious adverse drug reactions have attracted more and more attention. Series of caffeoylquinic acids in QKL are widely suspected to be the allergens responsible for these adverse drug reactions. Therefore, pharmacokinetic studies of the caffeoylquinic acids are needed. In this paper, a simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of chlorogenic acid, neochlorogenic acid, baicalin, geniposide, cholic acid and hyodeoxycholic acid in rat plasma. Chromatographic separation was achieved on a BEH C18 column by a gradient elution at a flow rate of 0.40 mL/min in only 6.0 min. All analytes were monitored by multiple reaction monitoring mode with negative electrospray ionization. The calibration curves of these analytes were all linear (r > 0.9978) over wide concentration ranges. The intra- and inter- day precisions (relative standard deviations) were within 14.3% and accuracy (relative error) ranged from -6.8 to 4.8%. The mean recoveries ranged from 74.5 to 105.6%. This validated method was successfully applied to the pharmacokinetic study of the six analytes in rats following an intravenous administration of QKL injection.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/farmacocinética , Ácido Quínico/análogos & derivados , Espectrometria de Massas em Tandem/métodos , Administração Intravenosa , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Masculino , Ácido Quínico/administração & dosagem , Ácido Quínico/farmacocinética , Ratos , Ratos Sprague-Dawley , Sensibilidade e EspecificidadeRESUMO
A feeding study was carried out in which six healthy ileostomists ingested a juice drink containing a diversity of dietary (poly)phenols derived from green tea, apples, grapes and citrus fruit. Ileal fluid and urine collected at intervals over the ensuing 24 h period were then analysed by HPLC-MS. Urinary excretions were compared with results obtained in an earlier study in which the juice drink was ingested by ten healthy control subjects with an intact colon. Some polyphenol components, such as (epi)catechins and (epi)gallocatechin(s), were excreted in urine in similar amounts in ileostomists and subjects with an intact colon, demonstrating that absorption took place principally in the small intestine. In the urine of ileostomists, there were reduced levels of other constituents, including hesperetin-7-O-rutinoside, 5-O-caffeoylquinic acid and dihydrochalcones, indicating their absorption in both the small and large intestine. Ileal fluid analysis revealed that even when absorption occurred in the small intestine, in subjects with a functioning colon a substantial proportion of the ingested components still pass from the small into the large intestine, where they may be either absorbed before or after catabolism by colonic bacteria.
Assuntos
Bebidas/análise , Intestino Grosso/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Polifenóis/administração & dosagem , Polifenóis/farmacocinética , Absorção , Adulto , Idoso , Disponibilidade Biológica , Catequina/administração & dosagem , Catequina/farmacocinética , Chalconas/farmacocinética , Chalconas/urina , Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/farmacocinética , Ácido Clorogênico/urina , Cromatografia Líquida de Alta Pressão , Citrus/química , Dieta , Feminino , Hesperidina/farmacocinética , Hesperidina/urina , Humanos , Absorção Intestinal/efeitos dos fármacos , Intestino Grosso/metabolismo , Intestino Delgado/metabolismo , Masculino , Malus/química , Pessoa de Meia-Idade , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacocinética , Ácido Quínico/urina , Chá/química , Vitis/químicaRESUMO
4,5-O-Dicaffeoylquinic acid methyl ester (1) was anaerobically incubated with human intestinal flora and four biotransformation products (2-5) were obtained. Their structures were elucidated as 3,4-O-dicaffeoylquinic acid methyl ester (2), 3-hydroxyphenylpropionic acid (3), trans-caffeic acid (4) and 3,4-dihydroxyphenylpropionic acid (5) on the basis of their spectroscopic data. Using high-performance liquid chromatography equipped with a diode array detector, chromatographic separation of 1-5 was performed on an analytical C18 column. The time course of the biotransformation was studied to probe into the biotransformation mechanism of 1 by human intestinal flora. In addition, the inhibitory activity of the parent compound 1 and its four main biotransformation products 2-5 on the inhibition of nitric oxide production induced by lipopolysaccharide in macrophage cell line RAW 264.7 and their DPPH free radical-scavenging activity in cell-free bioassay system were estimated.
Assuntos
Antioxidantes/farmacologia , Intestinos/microbiologia , Óxido Nítrico/biossíntese , Ácido Quínico/análogos & derivados , Biotransformação , Humanos , Limite de Detecção , Ácido Quínico/farmacocinéticaRESUMO
A specific and reliable HPLC-MS/MS method was developed and validated for the simultaneous determination of four dicaffeoylquinic acids (DCQA): 3,4-DCQA, 1,5-DCQA, 3,5-DCQA and 4,5-DCQA. The analytes were separated on a C18 column (150 mm × 2.1 mm, 1.8 µm) and a triple-quadrupole mass spectrometry equipped with an electrospray ionization (ESI) source was applied for detection. The plasma sample was prepared by a liquid-liquid extraction method and the recovery for the four analytes was around 80%. The calibration curves were linear over a concentration range of 10.6-1060.0 ng/mL for 3,4-DCQA, 19.2-1920.0 ng/mL for 1,5-DCQA, 14.0-2900.0 ng/mL for 3,5-DCQA, 9.7-970.0 ng/mL for 4,5-DCQA. The intra-day and inter-day precision was less than 15% and the relative error (RE) were all within ±15%. The validated method was successfully applied to a pharmacokinetics study in rats after oral administration of the extracts of Ainsliaea fragrans cham (a traditional Chinese herb).
Assuntos
Ácido Clorogênico/análogos & derivados , Cromatografia Líquida de Alta Pressão/métodos , Ácido Quínico/análogos & derivados , Espectrometria de Massas em Tandem/métodos , Animais , Ácido Clorogênico/sangue , Ácido Clorogênico/farmacocinética , Estabilidade de Medicamentos , Medicamentos de Ervas Chinesas , Masculino , Ácido Quínico/sangue , Ácido Quínico/farmacocinética , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
KZ-41, a quinic acid derivative, significantly reduces mortality in a murine model of hematopoietic acute radiation syndrome. The purpose of this study was to evaluate the systemic pharmacokinetics, elimination, and oral bioavailability of KZ-41 in rats. Male Sprague-Dawley rats (n = 6 per group) received a single dose (10 mg/kg) of KZ-41 administered either intravenously via the jugular vein or orally via gavage. In vitro stability was determined using both rat liver microsomes and the bacteria Gluconobacter oxydans. KZ-41 concentrations were determined using LC-MS/MS (liquid chromatography tandom mass spectrometry). Half-life of KZ-41 was ≈3 hr after either intravenous or oral administration. Mean volume of distribution was 3.3 L/kg. Extent of absorption (F) after oral administration was estimated to be ~100%, which was consistent with the finding that KZ-41 was stable to liver microsomal and bacterial degradation. Following intravenous administration, KZ-41 demonstrated a medium clearance and volume of distribution with a terminal half-life of ≈3 hr. KZ-41 was rapidly and completely absorbed (F â 1), which was consistent with the findings that KZ-41 is resistant to presystemic elimination mechanisms (i.e. enteric bacterial degradation and hepatic metabolism). Thus, KZ-41 represents an excellent candidate for further development as an orally available agent for the mitigation of radiation injury.