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1.
Chin J Nat Med ; 18(3): 234-240, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32245594

RESUMO

Azithromycin and Chinese medicine forsythia are often used together to treat pediatric mycoplasma infections in China. We aimed to investigate the pharmacokinetic interaction of Forsythia suspensa extract and azithromycin after single and co-intravenous administration in rats. Male Sprague-Dawley rats received single (Forsythia suspensa extract or azithromycin) treatment or co-administration of Forsythia suspensa extract and azithromycin. Blood samples were collected at scheduled times, and drug concentrations were determined by HPLC-UV or HPLC-MS/MS methods. Both non-compartmental analyses and nonlinear mixed-effects modeling approaches were applied to fit pharmacokinetic data and evaluate the impact of co-administration. Pharmacokinetic analysis showed that the area under the curve of azithromycin and forsythiaside increased, and clearance decreased significantly (P < 0.05), after co-administration. The in vivo behavior of both azithromycin and forsythiaside could be appropriately described by the two-compartmental model. The final population pharmacokinetic model indicated that co-administration decreased the central volume of azithromycin and forsythiaside clearance significantly. Co-administration of Forsythia suspensa extract and azithromycin significantly decreased the clearance and increased exposure for both drugs. Pharmacokinetic data suggest that drug co-administration may increase efficiency.


Assuntos
Azitromicina/farmacocinética , Glicosídeos/farmacocinética , Extratos Vegetais/farmacocinética , Administração Intravenosa , Animais , Área Sob a Curva , Quimioterapia Combinada , Forsythia/química , Masculino , Ratos Sprague-Dawley
2.
Phytomedicine ; 67: 153161, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31911401

RESUMO

BACKGROUND: Therapeutic applications of Fuzi (lateral root of Aconitum carmichaeli Debx) are seriously concerned with its toxic effects. Strategies and approaches to reducing toxicity are of great interest. PURPOSE: We aimed to characterize the diurnal rhythm of Fuzi toxicity, and to determine the role of metabolism and pharmacokinetics in generating toxicity rhythmicity. METHODS: Toxicity was determined based on assessment of heart injury and animal survival after dosing mice with Fuzi decoction at different circadian time points. Circadian clock control of pharmacokinetics and toxicity was investigated using Bmal1-deficient (Bmal1-/-) mice. RESULTS: Fuzi exhibited a diurnal rhythmicity in cardiotoxicity (reflected by plasma CK-MB and LDH levels). The highest level of toxicity was observed at ZT10 (5 PM), while the lowest level of toxicity occurred at ZT22 (5 AM). Also, a higher mortality rate was observed at ZT10 and lower mortality rates at other times of the day. ZT10 dosing of Fuzi generated higher systemic exposures of three toxic alkaloid ingredients aconitine (AC), hypaconitine (HA) and mesaconitine (MA) compared to ZT22. This was accompanied by reduced the formation of the metabolites (N-deethyl-AC, didemethyl-HA and 2­hydroxyl­MA) at ZT10. Bmal1 ablation resulted in an increased level of Fuzi toxicity at ZT22, while having no influences when drug was dosed at ZT10. As a consequence, circadian time-dependent toxicity of Fuzi was lost in Bmal1-deficient mice. In addition, Bmal1 ablation increased the plasma concentrations of AC, HA and MA in mice after oral gavage of Fuzi, and reduced formation of their metabolites (N-deethyl-AC, didemethyl-HA and 2­hydroxyl­MA). Moreover, Fuzi metabolism in wild-type liver microsomes was more extensive at ZT22 than at ZT10. Bmal1 ablation abrogated circadian time-dependency of hepatic Fuzi metabolism. CONCLUSIONS: Fuzi chronotoxicity in mice was attributed to time-varying hepatic metabolism and systemic exposure regulated by circadian clock. The findings may have implications in reducing Fuzi toxicity with a chronotherapeutic approach.


Assuntos
Aconitum/química , Relógios Circadianos/efeitos dos fármacos , Extratos Vegetais/farmacocinética , Extratos Vegetais/toxicidade , Fatores de Transcrição ARNTL/genética , Aconitina/análogos & derivados , Aconitina/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão/métodos , Relógios Circadianos/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Microssomos Hepáticos/efeitos dos fármacos , Testes de Toxicidade/métodos
3.
Recent Pat Biotechnol ; 14(1): 16-32, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31438835

RESUMO

BACKGROUND: Recently, it has been established that simultaneous saccharification and fermentation is a potent technique for the detoxification of harmful plant materials. OBJECTIVE: Following encouraging simultaneous medicinal applications of snail slime and yeast, we exploited their hydrolytic and fermentation potentials to prevent toxicities of the selected floras; Erythrodontium barteri (EB), bracken fern (BF), and crustose lichens (CL). The applicability of the saccharification process has been described in a patent (WO2005010193A2). METHODS: The plants were bioprocessed using snail digestive juice and yeast slurry and their health effects were evaluated. Seventy rats were divided equally into groups, treated with single doses of aqueous extracts of the plants and their bioprocessed forms, and compared with control rats. RESULTS: The plants showed very high antinutrients levels, which significantly reduced after SSF with enhanced flavonoids, alkaloids and phenols. Potential alterations of WBC differentials, RBC, liver and renal function markers indices were mitigated by bioprocessed extracts. MDA, SOD, GRase, XO and XDH levels in rats administered the bEB and CL were equivalent to the levels found for the control rats. Some bioprocessed plants produced unaltered insulin, ghrelin, and leptin levels. The bioprocessed extracts, when compared to the effects of unprocessed extracts, produced lower TNF-α, Caspase-3, and adiponectin levels and mitigated the potential suppression of Na+/K+-ATPase levels. Potential depletion of inhibin-B, testosterone, estrogen, and prolactin was mitigated after bioprocessing. CONCLUSION: This study, thus, validates the application of bioprocessing using snail digestive juice and yeast as an effective approach to reduce the potential toxicities of harmful plants.


Assuntos
Produtos Biológicos , Fígado , Extratos Vegetais , Animais , Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Biotransformação , Glicemia/efeitos dos fármacos , Embriófitas/química , Feminino , Testes Hematológicos , Líquens/química , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Patentes como Assunto , Extratos Vegetais/química , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacocinética , Extratos Vegetais/toxicidade , Ratos , Ratos Wistar , Caramujos/química , Leveduras/química
4.
Biomed Chromatogr ; 34(1): e4714, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31633806

RESUMO

Eucommia ulmoides Oliv. (E. ulmoides) is a valuable and nourishing medicinal herb in China that has been used in the treatment of hypertension. Given the fact that most traditional Chinese medicine is mainly used to treat disease, investigating the pharmacokinetics of traditional Chinese medicines in the pathological state is more useful than that in the normal state. However, the differences in the absorption kinetics of active ingredients of E. ulmoides extract between pathological and physiological conditions have not been reported. Therefore, in this study, the rat intestinal in situ circulatory perfusion model was used to investigate the differences in absorption kinetics of seven active ingredients of E. ulmoides extract in normal and spontaneously hypertensive rats, namely, genipinic acid, protocatechuic acid, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, (+)-pinoresinol di-O-ß-D-glucopyranoside and (+)-pinoresinol 4'-O-ß-D-glucopyranoside. Our results indicate that the pathological state of spontaneous hypertension may change the absorption of active components of E. ulmoides extracts, and these findings may provide a reference for improving the rational use of E. ulmoides in the clinic.


Assuntos
Eucommiaceae , Absorção Intestinal , Extratos Vegetais , Animais , Anti-Hipertensivos/análise , Anti-Hipertensivos/farmacocinética , Líquidos Corporais/química , Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/análise , Ácido Clorogênico/farmacocinética , Furanos/análise , Furanos/farmacocinética , Hidroxibenzoatos/análise , Hidroxibenzoatos/farmacocinética , Lignanas/análise , Lignanas/farmacocinética , Extratos Vegetais/análise , Extratos Vegetais/farmacocinética , Ratos , Ratos Endogâmicos SHR , Ratos Wistar
5.
J Pharm Biomed Anal ; 177: 112820, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31476432

RESUMO

Ginger, the rhizome of Zingiber officinale Roscoe is of great importance in the traditional medicine for the treatment of various diseases. More than 400 constituents have been reported in the plant, the most important ones being the gingerol and shogaol derivatives. Positive effects of ginger extracts and isolated [6]-gingerol have been proved in animal models of anxiety, Alzheimer's disease, Parkinson's disease and epilepsy. Taken in consideration these promising positive effects of ginger and its constituents in the central nervous system, the isolation of gingerol and shogaol derivatives ([6]-gingerol (1), [8]-gingerol (2), [10]-gingerol (3), [6]-shogaol (4), [10]-shogaol (5), 1-dehydro-[6]-gingerdione (6), 1-dehydro-[10]-gingerdione (7)) and investigation of their transcellular passive diffusion across the blood-brain barrier (BBB) were carried out. For this purpose, a Parallel Artificial Membrane Permeability Assay for the Blood-Brain Barrier (PAMPA-BBB) was chosen that had previously been validated for natural compounds. Based on our results, [6]-gingerol, [8]-gingerol and [6]-shogaol were found to be able to penetrate the BBB via passive diffusion, suggesting them to contribute to the positive effects of ginger extracts in the central nervous system.


Assuntos
Barreira Hematoencefálica/metabolismo , Catecóis/farmacologia , Catecóis/farmacocinética , Álcoois Graxos/farmacocinética , Gengibre/química , Extratos Vegetais/farmacocinética , Animais , Barreira Hematoencefálica/química , Catecóis/química , Catecóis/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Difusão , Álcoois Graxos/química , Álcoois Graxos/isolamento & purificação , Lipídeos/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas/métodos , Membranas Artificiais , Permeabilidade , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Suínos
6.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3170-3177, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602869

RESUMO

The intestinal absorption characteristics of ten iridoid glycosides and phenolic acids in the Pterocephali Herba were evaluated via rat intestinal valgus model. The intestinal sac fluids at different time after administration of high,medium and low concentrations of Pterocephali Herba extract were collected and ten chemical components in fluid samples were detected by UPLC-PDA. Accumulative absorbed doses( Q) and absorption rate constants( Ka) of ten chemical constituents were calculated,while proportions between Pterocephali Herba extract and intestinal absorption liquid were compared. The results showed that the intestinal absorption of 10 chemical components was linear absorption( R2>0. 9) at different concentrations,which accorded with the zero-order absorption rate. The absorption rate constant was related to the concentration of the drug and the intestinal site,which indicated that intestinal adsorption mechanism of the components were passive diffusion and active transport. Proportions of chemical constituents in intestinal sac fluid were different from those in Pterocephali Herba extract. Therefore,those ten chemical components in Pterocephali Herba extract can be absorbed in whole intestine. Everted intestinal sac model can be used to evaluate intestinal absorption characteristics of ingredients in Pterocephali Herba extract effectively.


Assuntos
Caprifoliaceae/química , Medicamentos de Ervas Chinesas/farmacocinética , Absorção Intestinal , Extratos Vegetais/farmacocinética , Animais , Intestinos , Ratos , Ratos Sprague-Dawley
7.
Complement Ther Med ; 46: 87-94, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31519293

RESUMO

BACKGROUND: caffeine is a major constituent in numerous foods, beverages, dietary supplements and medications.Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav, and Salvia miltiorrhiza Bunge are traditional medicines commonly used in Asia. OBJECTIVES: to compare the pharmacokinetics of caffeine in humans before and after consuming an aqueous extract of A. dahurica or S. miltiorrhiza, and to propose a mechanistic explanation for in vivo caffeine metabolism inhibition based on in vitro data obtained with human liver microsomes. METHODS: Each of the four human volunteers was given a single oral dose of caffeine before and after consuming an A. dahurica or S. miltiorrhiza extract. Saliva samples were collected from the volunteers at pre-determined time points after receiving caffeine. The saliva samples were analyzed for unchanged caffeine using liquid chromatography. RESULTS: A. dahurica and S. miltiorrhiza extracts were capable of inhibiting caffeine metabolism in the human volunteers. In a separate study, cytochrome (CYP) 1A2-mediated caffeine demethylase activity was studied in incubation containing human liver microsomes, ß-nicotinamide adenine dinucleotide phosphate, and an herbal extract (or a pure bioactive chemical from the herbs). In all cases, CYP1A2 activity was decreased with an increasing inhibitor concentration, confirming the inhibition of caffeine metabolism in vivo. Caffeine metabolism inhibition most likely involved the competitive and/or non-competitive mechanism. CONCLUSION: Because a high level of caffeine in the plasma may result in adverse health effects in humans, care must be exercised when caffeine is consumed together with A. dahurica or S. miltiorrhiza.


Assuntos
Angelica/química , Cafeína/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Extratos Vegetais/farmacocinética , Salvia miltiorrhiza/química , Adulto , Citocromo P-450 CYP1A2/metabolismo , Medicamentos de Ervas Chinesas/química , Feminino , Humanos , Masculino , Extratos Vegetais/química , Adulto Jovem
8.
BMC Complement Altern Med ; 19(1): 235, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477089

RESUMO

BACKGROUND: Oxyresveratrol is a major bioactive component derived from the heartwood of Artocarpus lacucha. This compound exerts several biological activities, including neuroprotective effects in vitro and in vivo. However, there is limited pharmacokinetic information on this compound, especially its distribution in neuronal tissue and its route of excretion. The aim of this study was to investigate the pharmacokinetic profiles of oxyresveratrol alone and in combination with piperine as a bioenhancer in rats. METHODS: Male Wistar rats were administered with oxyresveratrol 10 mg/kg, oxyresveratrol 10 mg/kg plus piperine 1 mg/kg via intravenous or oxyresveratrol 100 mg/kg, oxyresveratrol 100 mg/kg plus piperine 10 mg/kg via oral gavage. Plasma, internal organs, urine, and feces were collected. Determination of the oxyresveratrol concentration in biological samples was performed by liquid chromatography tandem mass spectrometry. RESULTS: The combination with piperine had shown a significantly higher maximum concentration in plasma approximately 1500 µg/L within 1-2 h after oral dosing, and could increase oral bioavailability of oxyresveratrol approximately 2-fold. Oxyresveratrol could widely distributed most of the internal organs with a tissue to plasma ratio of 10-100 fold within 5 min after dosing. Urinary excretion of oxyresveratrol glucuronide was the major route of excretion after administration of oxyresveratrol alone and in combination with piperine. CONCLUSION: The addition of piperine could enhance some of the pharmacokinetic properties of oxyresveratrol via both intravenous and oral administration. This pharmacokinetic information will be useful for appropriate strategies to develop oxyresveratrol as a phytopharmaceutical product.


Assuntos
Alcaloides , Benzodioxóis , Piperidinas , Extratos Vegetais , Alcamidas Poli-Insaturadas , Estilbenos , Administração Intravenosa , Administração Oral , Alcaloides/administração & dosagem , Alcaloides/sangue , Alcaloides/farmacocinética , Alcaloides/urina , Animais , Artocarpus , Benzodioxóis/administração & dosagem , Benzodioxóis/sangue , Benzodioxóis/farmacocinética , Benzodioxóis/urina , Interações Medicamentosas , Masculino , Piperidinas/administração & dosagem , Piperidinas/sangue , Piperidinas/farmacocinética , Piperidinas/urina , Extratos Vegetais/administração & dosagem , Extratos Vegetais/sangue , Extratos Vegetais/farmacocinética , Extratos Vegetais/urina , Alcamidas Poli-Insaturadas/administração & dosagem , Alcamidas Poli-Insaturadas/sangue , Alcamidas Poli-Insaturadas/farmacocinética , Alcamidas Poli-Insaturadas/urina , Ratos , Ratos Wistar , Estilbenos/administração & dosagem , Estilbenos/sangue , Estilbenos/farmacocinética , Estilbenos/urina
9.
Biomed Chromatogr ; 33(12): e4674, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31376170

RESUMO

Tyrosine kinase inhibitor treatments for chronic myeloid leukaemia based on nilotinib (NIL), dasatinib (DAS) and imatinib (IMA) have improved patient quality of life and have turned chronic myeloid leukemia from a fatal disease into a chronic disease. Dandelion is a rich source of phenolic compounds with strong biological properties, and the effects of using this plant in the treatment of different illnesses can be linked to the presence of various polyphenols found in the different parts of the plant. Thus, dandelion can potentially be used as a nutraceutical (dietary antioxidant) to prevent different disorders associated with oxidative stress, i.e. cardiovascular disorders, cancer and inflammatory processes. Mutual interference between a drug and a food constituent may result in altered pharmacokinetics of the drug and undesired or even dangerous clinical situations. In the present study, a bioanalytical ultra performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) method was developed and validated for the quantification of DAS, IMA and NIL in rat plasma. Sample preparation was carried out using solid-phase extraction with C18 cartridges with a good extraction recovery of ≥94.37% for the three drugs. The method was fully validated as per the US Food and Drug Administration guidelines.


Assuntos
Dasatinibe/farmacocinética , Interações Ervas-Drogas , Mesilato de Imatinib/farmacocinética , Extratos Vegetais/farmacocinética , Pirimidinas/farmacocinética , Taraxacum , Animais , Cromatografia Líquida de Alta Pressão , Dasatinibe/sangue , Dasatinibe/química , Estabilidade de Medicamentos , Mesilato de Imatinib/sangue , Mesilato de Imatinib/química , Limite de Detecção , Modelos Lineares , Extratos Vegetais/química , Raízes de Plantas/química , Pirimidinas/sangue , Pirimidinas/química , Ratos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
10.
Molecules ; 24(17)2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31466218

RESUMO

Acanthus ilicifolius herb (AIH), the dry plant of Acanthus ilicifolius L., has long been used as a folk medicine for treating acute and chronic hepatitis. Phenylethanoid glycosides (PhGs) are one family of the main components in AIH with hepatoprotective, antioxidant, and anti-inflammatory activities. In this study, the pharmacokinetics of AIH was investigated preliminarily by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS). A simultaneously quantitative determination method for four PhGs (acteoside, isoacteoside, martynoside, and crenatoside) in rat plasma was first established by UPLC-MS/MS. These four PhGs were separated with an ACQUITY UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm) by gradient elution (mobile phase: MeCN and 0.1% formic acid in water, 0.4 mL/min). The mass spectrometry detection was performed using negative electrospray ionization (ESI-) in multiple reaction monitoring (MRM) mode. By the established method, the preliminary pharmacokinetics of AIH was elucidated using the kinetic parameters of the four PhGs in rat plasma after intragastric administration of AIH ethanol extract. All four PhGs showed double peaks on concentration-time curves, approximately at 0.5 h and 6 h, respectively. Their elimination half-lives (t1/2) were different, ranging from 3.42 h to 8.99 h, although they shared similar molecular structures. This work may provide a basis for the elucidation of the pharmacokinetic characteristics of bioactive components from AIH.


Assuntos
Acanthaceae/química , Glicosídeos/sangue , Extratos Vegetais/administração & dosagem , Animais , Ácidos Cafeicos/sangue , Ácidos Cafeicos/farmacocinética , Cromatografia Líquida , Glucosídeos/sangue , Glucosídeos/farmacocinética , Glicosídeos/farmacocinética , Masculino , Fenóis/sangue , Fenóis/farmacocinética , Extratos Vegetais/farmacocinética , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
11.
J Physiol Pharmacol ; 70(2)2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31443093

RESUMO

Standardized WS-1442 extract from Crataegus oxycantha (hawthorn) leaves and berries is one of the most widely studied preparations received from hawthorn. This popular substance is known from its positive influence on the cardiovascular system. The current research aimed to evaluate the optimal dose of standardized WS-1442 extract and the most beneficial period for its use. The study analysis was based on experiments previously conducted on male Sprague-Dawley rats (n = 152). The animals were divided into subgroups to examine the relationship between the dose-dependent (n = 96) and time-dependent (n = 56) effects of the mentioned extract. The research was performed based on the modified early reperfusion-induced arrhythmias model in vivo. The following parameters were assessed during the study: efficiency of mortality index reduction, reduction of ventricular arrhythmias incidences as well as the influence of standardized WS-1442 extract on hemodynamic parameters and amount of biochemical marker of cardiac tissue damage (creatine kinase). The current study revealed the dose- and time-dependent cardioprotective effect of standardized WS-1442 extract. It was expressed by mortality index reduction, decrease in the incidence and duration of severe ventricular arrhythmias and decline in the total amount of creatine kinase. Analyzed data coming from a model of reperfusion-induced arrhythmias in rats suggests that standardized WS-1442 extract is a potent cardioprotective agent whose action depends on both dose and intake time.


Assuntos
Arritmias Cardíacas/tratamento farmacológico , Sistema Cardiovascular/efeitos dos fármacos , Crataegus/química , Flavonoides/farmacologia , Extratos Vegetais/farmacocinética , Animais , Arritmias Cardíacas/metabolismo , Cardiotônicos/farmacologia , Sistema Cardiovascular/metabolismo , Creatina Quinase/metabolismo , Modelos Animais de Doenças , Masculino , Folhas de Planta/química , Ratos , Ratos Sprague-Dawley , Reperfusão/métodos
12.
Int J Mol Sci ; 20(17)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443458

RESUMO

Natural compounds, in recent years, have attracted significant attention for their use in the prevention and treatment of diverse chronic diseases as they are devoid of major toxicities. Boswellic acid (BA), a series of pentacyclic triterpene molecules, is isolated from the gum resin of Boswellia serrata and Boswellia carteri. It proved to be one such agent that has exhibited efficacy against various chronic diseases like arthritis, diabetes, asthma, cancer, inflammatory bowel disease, Parkinson's disease, Alzheimer's, etc. The molecular targets attributed to its wide range of biological activities include transcription factors, kinases, enzymes, receptors, growth factors, etc. The present review is an attempt to demonstrate the diverse pharmacological uses of BA, along with its underlying molecular mechanism of action against different ailments. Further, this review also discusses the roadblocks associated with the pharmacokinetics and bioavailability of this promising compound and strategies to overcome those limitations for developing it as an effective drug for the clinical management of chronic diseases.


Assuntos
Triterpenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Doença Crônica/tratamento farmacológico , Humanos , Camundongos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Extratos Vegetais/farmacologia , Relação Estrutura-Atividade , Triterpenos/administração & dosagem , Triterpenos/química , Triterpenos/farmacocinética
13.
Molecules ; 24(17)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443519

RESUMO

Orthosiphon stamineus Benth. (OS) is a traditional folk medicine for the treatment of kidney stones and other urinary tract diseases. In this study, a rapid and sensitive Ultra high-performance liquid chromatography (UHPLC)-MS/MS approach was established and validated for the simultaneous quantification of nine bioactive components in rat plasma. The nine components from OS extract detected in rat plasma were danshensu, protocatechuic acid, caffeic acid, rosmarinic acid, salvianolic acid A, salvianolic acid B, cichoric acid, sinensetin and eupatorin. After liquid-liquid extraction with ethyl acetate, the plasma samples were subjected to a triple quadrupole mass spectrometer employing electrospray ionization (ESI) technique and operating in multiple reaction monitoring (MRM) with both positive and negative ion modes. The standard curves showed good linear regression (r > 0.9915) over the concentration range for the nine analytes. The inter-day and intra-day precision and accuracy were found to be within 15% of the nominal concentration. The recovery and stability of nine compounds were all demonstrated to be within acceptable limits. The approach was successfully applied to investigate the pharmacokinetic analysis of the nine bioactive components after oral administration of OS extract in rats.


Assuntos
Cromatografia Líquida de Alta Pressão , Orthosiphon/química , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Espectrometria de Massas em Tandem , Animais , Monitoramento de Medicamentos , Estrutura Molecular , Ratos
14.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1126-1127: 121737, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31377565

RESUMO

Gamboge, a dried resin secreted by Garcinia hanburyi Hook. f. (Guttiferae), possesses remarkable anticancer activity. However, due to toxicity, it must be processed before use in clinics. Xanthones are the main bioactive ingredients in gamboge. In order to elucidate the influence of processing technology on pharmacological properties of gamboge, an efficient, sensitive, and selective ultra-performance liquid chromatography coupled with triple quadruple mass spectrometry (UPLC-MS/MS) method of five critical xanthones, including ß-morellic acid (ß-MA), isogambogenic acid (IGNA), gambogenic acid (GNA), R-gambogic acid (GA), and S-GA in rat plasma was established for a comparative pharmacokinetics study of these xanthones after oral administration of crude and processed G. hanburyi extracts. The chromatographic separation of these five xanthones along with an internal standard (I.S.) was carried out on a Waters Acquity UPLC BEH C8 column with a gradient elution method using acetonitrile/0.1% formic acid-water as mobile phases. The eluate was detected by multiple-reaction monitoring (MRM) scanning with an electrospray ionization source operating in the positive ionization mode. Sample preparation involved a liquid-liquid extraction of the five analytes with ethyl acetate. Deoxyschizandrin was employed as an internal standard. This assay method was validated for selectivity, linearity, intra-day and inter-day precision, accuracy, recovery, matrix effect, and stability. The results revealed that the calibration curves displayed good linear regression (r > 0.995), and the lower limit of quantification (LLOQ) was <5.52 ng/mL for each analyte. The intra-day and inter-day precision (RSD) of the five xanthones at low, medium, and high levels was <10.58%, and the bias of the accuracy ranged from -8.54 to 10.2%. All other parameters fulfilled the FDA criteria for bioanalytical validation. In addition, the assay was successfully applied to the determination and pharmacokinetic study of these five xanthones after oral administration of crude and processed gamboge. Furthermore, Cmax of GNA and AUC0-t of IGNA were increased significantly (P < 0.05) after processing, while AUC0-t of ß-MA, R-GA, and S-GA decreased remarkably (P < 0.05), which suggested that processing exerted different effects on the absorption of xanthones. The results might be valuable for the clinical reasonable application and understanding the processing mechanism of gamboge.


Assuntos
Garcinia , Extratos Vegetais/farmacocinética , Xantonas/sangue , Xantonas/farmacocinética , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão/métodos , Estabilidade de Medicamentos , Modelos Lineares , Masculino , Extratos Vegetais/administração & dosagem , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem/métodos , Xantonas/química
15.
Molecules ; 24(14)2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31323835

RESUMO

We aimed to develop a sensitive method for detecting 13 ginsenosides using liquid chromatography-tandem mass spectrometry and to apply this method to pharmacokinetic studies in human following repeated oral administration of red ginseng extract. The chromatograms of Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3, Rh2, F1, compound K (CK), protopanaxadiol (PPD), and protopanaxatriol (PPT) in human plasma were well separated. The calibration curve range for 13 ginsenosides was 0.5-200 ng/mL and the lower limit of quantitation was 0.5 ng/mL for all ginsenosides. The inter- and intra-day accuracy, precision, and stability were less than 15%. Among the 13 ginsenosides tested, nine ginsenosides (Rb1, Rb2, Rc, Rd, Rg3, CK, Rh2, PPD, and PPT) were detected in the human plasma samples. The plasma concentrations of Rb1, Rb2, Rc, Rd, and Rg3 were correlated with the content in red ginseng extract; however, CK, Rh2, PPD, and PPT were detected although they are not present in red ginseng extract, suggesting the formation of these ginsenosides through the human metabolism. In conclusion, our analytical method could be effectively used to evaluate pharmacokinetic properties of ginsenosides, which would be useful for establishing the pharmacokinetic-pharmacodymic relationship of ginsenosides as well as ginsenoside metabolism in humans.


Assuntos
Ginsenosídeos/sangue , Ginsenosídeos/química , Panax/química , Extratos Vegetais/sangue , Extratos Vegetais/química , Ginsenosídeos/farmacocinética , Humanos , Redes e Vias Metabólicas , Estrutura Molecular , Extratos Vegetais/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem
16.
BMC Res Notes ; 12(1): 369, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262338

RESUMO

OBJECTIVES: Consumption of fish/seafood is clearly linked to higher mercury levels in human tissue samples. However, correlations between methylmercury (MeHg) intakes calculated from dietary surveys and mercury body burdens are usually weak and can vary across populations. Different factors may affect MeHg absorption, distribution, metabolism and excretion, including co-exposures to phytochemicals and antibiotics, which were shown to affect mercury body burdens in rodents. Based on the observation that rat pups developmentally exposed to MeHg and a Rhododendron tomentosum extract (Labrador Tea) presented significantly higher blood mercury levels at weaning compared to pups exposed to MeHg alone, the modulation of MeHg toxicokinetics by Labrador Tea was further investigated in adult rats. RESULTS: Total mercury levels were quantified in the blood, liver, kidney and feces of adult male rats exposed to MeHg (1.2 mg/kg bodyweight/day, for 3 weeks) administered either alone or in combination with Labrador Tea (100 mg/kg bodyweight/day) or with an antibiotics cocktail (to inhibit MeHg demethylation by gut bacteria). While the reduced fecal excretion and higher blood mercury levels expected from antibiotics-treated rats were observed, mercury levels in samples from Labrador Tea-treated rats were not significantly different from those measured in samples from rats exposed to MeHg alone.


Assuntos
Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Compostos de Metilmercúrio/farmacocinética , Extratos Vegetais/farmacocinética , Rhododendron/química , Animais , Antibacterianos/administração & dosagem , Transporte Biológico/efeitos dos fármacos , Fezes/química , Rim/química , Rim/metabolismo , Ledum/química , Fígado/química , Fígado/metabolismo , Masculino , Neomicina/administração & dosagem , Penicilinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Estreptomicina/administração & dosagem
17.
J Ethnopharmacol ; 241: 112023, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31195031

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Woodfordia fruticosa is traditionally used in the Ayurvedic system of medicine for the treatment of diarrhoea, poisoning, menstrual disorders, ulcers and fertility. In the present study, we report a standardized extract preparation through modern scientific approach for anti-ulcer activity. MATERIALS AND METHODS: The hydro-alcoholic extract of flowers of W. fruticosa was standardized using four chemical markers. The standardized extract was coded as ICB014. HPLC method was developed for identification and quantification of Gallic Acid, Oenothein-C, Quercetin and Kaempferol. Based on the prior published H+, K+-ATPase activity and Anti-bacterial activity against Helicobacter pylori of ICB014, was evaluated for its in-vivo efficacy in gastric ulcers models in rats followed by regulatory safety studies. RESULTS: The extract demonstrated efficacy at 31.25-62.5 mg/kg in gastric ulcer models. The extract was safe by oral route up to 2000 mg/kg in a single dose and NOAEL of 800 mg/kg in 28 days repeat study. Bioequivalent capsule formulation was prepared. CONCLUSIONS: The extract showed anti-ulcer potential and is ready for clinical evaluation.


Assuntos
Antiulcerosos/uso terapêutico , Extratos Vegetais/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Woodfordia , Animais , Antiulcerosos/farmacocinética , Antiulcerosos/toxicidade , Etanol , Feminino , Flores , Helicobacter pylori/efeitos dos fármacos , Ácido Clorídrico , Masculino , Camundongos , Fitoterapia , Extratos Vegetais/farmacocinética , Extratos Vegetais/toxicidade , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Testes de Toxicidade
18.
Food Chem Toxicol ; 131: 110586, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31202939

RESUMO

Ginkgo biloba extract (GBE) is a popular botanical dietary supplement used worldwide and the safety of use is a public health concern. While GBE is a complex mixture, the terpene trilactones and flavonol glycosides are believed to elicit the pharmacological and/or toxicological effects of GBE. In a National Toxicology Program (NTP) 2-year rodent bioassay with GBE, hepatotoxicity was observed in rodents (≥100 mg/kg in rats, ≥ 200 mg/kg in mice). Subsequently, questions arose about whether or not the GBE used in NTP studies was representative of other GBE products and how rodent doses are related to human doses. To address these, we generated systemic exposure data for terpene trilactones in male rats following oral administration of 30, 100, and 300 mg/kg GBE test article from the 2-year bioassay. Dose-normalized Cmax and AUC∞ for terpene trilactones from the current study were within 5-fold of published rodent studies using a standardized GBE preparation. Comparison of our rat systemic exposure data at 100 mg/kg GBE to published human data following ingestion of 240 mg GBE-containing product showed that the rat/human exposure multiple was 3-22, for terpene trilactones. These data demonstrate the relevance of NTP rodent toxicity data to humans.


Assuntos
Ginkgo biloba/química , Extratos Vegetais/farmacocinética , Administração Oral , Animais , Flavonóis/sangue , Ginkgolídeos/sangue , Humanos , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/metabolismo , Extratos Vegetais/toxicidade , Ratos Endogâmicos F344 , Toxicocinética
19.
J Microencapsul ; 36(2): 204-214, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31164027

RESUMO

Nigella sativa extract (NSE) was incorporated in alginate microcapsules using aerosolisation and homogenisation methods, respectively, with the aim of delivering high concentrations of the active species, thymoquinone (TQ), directly to sites of inflammation in the colon following oral administration. Encapsulation of NSE was accomplished either by direct loading or diffusion into blank microparticles. Microcapsules in the size range 40-60 µm exhibited significantly higher NSE loading up to 42% w/w and encapsulation efficiency (EE) up to 63% when the extract was entrapped by direct encapsulation compared with 4.1 w/w loading, 6.2% EE when NSE was incorporated by diffusion loading. Sequential exposure of samples to simulated intestinal fluids (SIFs) revealed that the microcapsules suppressed NSE release in simulated gastric fluid (SGF) for 2 h and SIF for 4 h and liberated most of the NSE content (80%) in simulated colonic fluid (SCF) over 18 h. NSE released in SCF at 12 h exhibited antioxidant activity, when measured using the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay at levels comparable with the activity of unencapsulated extract. These findings demonstrate the potential of oral alginate microcapsules as highly efficient, targeted carriers for colonic delivery of NSE in the treatment of inflammatory bowel disease.


Assuntos
Alginatos/química , Antioxidantes/administração & dosagem , Benzoquinonas/administração & dosagem , Portadores de Fármacos/química , Extratos Vegetais/administração & dosagem , Administração Oral , Antioxidantes/farmacocinética , Benzoquinonas/farmacocinética , Cápsulas/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Nigella sativa/química , Extratos Vegetais/farmacocinética
20.
Nutrients ; 11(6)2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31207874

RESUMO

Graviola leaves contain much vitamin U (vit U), but their sensory quality is not good enough for them to be developed as food ingredients. Addition of excipient natural ingredients formulated alongside vit U as active ingredients could enhance not only its sensory quality but also its bioavailability. The objectives of this study were to measure the bioaccessibility and intestinal cellular uptake of bioactive components, including rutin, kaempferol-rutinoside, and vit U, from steamed extract of graviola leaves (SGV) and SGV enriched with kale extract (SGK), and to examine how much they can detoxify nicotine in HepG2 cells. The bioaccessibility of vit U from SGV and SGK was 82.40% and 68.03%, respectively. The cellular uptake of vit U in SGK by Caco-2 cells was higher than that in SGV. Cotinine content converted from nicotine in HepG2 cells for 120 min was 0.22 and 0.25 µg/mg protein in 50 µg/mL of SGV and SGK, respectively, which were 2.86 and 3.57 times higher than the no-treatment control. SGK treatment of HepG2 cells upregulated CYP2A6 three times as much as did that of SGV. Our results suggest that graviola leaf extract enriched with excipient ingredients such as kale could improve vit U absorption and provide a natural therapy for detoxifying nicotine.


Assuntos
Annona/química , Inativação Metabólica/efeitos dos fármacos , Absorção Intestinal/fisiologia , Nicotina/metabolismo , Extratos Vegetais , Vitamina U , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Extratos Vegetais/química , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacocinética , Extratos Vegetais/farmacologia , Vitamina U/química , Vitamina U/metabolismo , Vitamina U/farmacocinética , Vitamina U/farmacologia
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