RESUMEN
Cancer is one of the greatest causes of death worldwide. With the development of surgery, radiotherapy, and medical agents, the outcomes of cancer patients have greatly improved. However, the underlying mechanisms of cancer are not yet fully understood. Recently, natural products have been proven to be beneficial for various conditions and have played important roles in the development of novel therapies. A substantial amount of evidence indicates that bioactive compounds could improve the outcomes of cancer patients via various pathways, such as endoplasmic reticulum stress, epigenetic modification, and modulation of oxidative stress. Here, we review the current evidence of bioactive compounds in natural products for the treatment of cancer and summarize the underlying mechanisms in this pathological process.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Productos Biológicos/química , Productos Biológicos/farmacología , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Antineoplásicos/uso terapéutico , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Productos Biológicos/uso terapéutico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Epigénesis Genética/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/prevención & control , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/orina , Factores de Transcripción/metabolismoRESUMEN
Septilin (Spt), a herbo-mineral formulation contains the extracts of Maharasanadi qoath, Tinospora cordifolia, Rubia cordifolia, Emblica officinalis, Moringa pterigosperma, Glycyrrhiza glabra and powders of Balsamodendron mukul and Shankha bhasma. In the present study, the anticlastogenic, antigenotoxic, antioxidant and histoprotective effects of Spt against cisplatin (Csp) induced toxicity in Swiss albino mice were investigated. The micronucleus (MN) test was used to assess the anticlastogenic potential of Spt (125, 250 and 500 mg/kg bw; p.o., 5 days) on somatic cells of mice. The sperm shape abnormality assay detects germinal nuclear damage, which induces spermatogenic dysfunction. Comet assay was employed to study the antigenotoxic potential of Spt on Csp (10 mg/kg bw; i.p.) induced DNA strand breaks in bone marrow cells of mice. The antioxidant enzyme activity of liver superoxide dismutase (SOD) and a biological antioxidant, reduced glutathione (GSH) were measured to determine its hepatoprotective property. The ability of Spt to protect against the histopathologic alterations accompanying Csp-induced liver and testicular injury was studied. The frequencies of MN induced by Csp in bone marrow and peripheral blood cells of mice were significantly decreased by the pre-treatment of Spt. Csp treatment increased the percentage of DNA strand breaks and depleted levels of SOD and GSH content along with histopathological changes. Supplementation of Spt attenuated the toxicity of Csp in liver and testes tissues possible viaimprovement of enzymatic and histological parameters toward normal. This study suggests that the protection offered by Spt against Csp-induced toxicity is partly related to the maintenance of the antioxidant system. Overall, this study shows the protective role of Spt against Csp-induced toxicity in somatic and male germinal cells of mice.
Asunto(s)
Antioxidantes , Cisplatino , Extractos Vegetales/farmacología , Extractos Vegetales/orina , Animales , Antioxidantes/metabolismo , Cisplatino/toxicidad , ADN , Glutatión/metabolismo , Masculino , Ratones , Minerales , Estrés Oxidativo , Superóxido Dismutasa/metabolismoRESUMEN
OBJECTIVE: People who use cocaine experience numerous sleep problems and often use cannabis to mitigate these problems. However, co-using cocaine and cannabis may result in worse sleep outcomes when compared to using cocaine only. The current study examined group differences in subjective sleep outcomes among people who use cocaine and people who co-use cocaine and cannabis. METHODS: Participants were 82 individuals with cocaine use disorder who were enrolled in a randomized clinical trial for cocaine treatment. Sleep outcomes, assessed at baseline prior to treatment, were measured with the Saint Mary's Hospital Sleep Questionnaire and included total sleep time, perceived sleep quality, difficulty falling asleep, and daytime alertness. Analysis of covariance and Kruskal-Wallis tests were used to compare sleep outcomes between participants with urine samples that tested positive for both cocaine and cannabis at baseline, those who tested positive for cocaine only, and those who tested negative for all drugs. RESULTS: Total reported sleep time was highest among those with a drug negative urine, followed by those with a cocaine positive urine and those who tested positive for cocaine and cannabis. There were no differences in perceived sleep quality, difficulty falling asleep, or daytime alertness between groups. CONCLUSIONS: People who co-use cocaine and cannabis may report reduced sleep time relative to those who only use cocaine. Co-use of cannabis may exacerbate sleep difficulties in people who use cocaine by decreasing total sleep time, although it is important to note that the groups each reported similar sleep quality. Implications for treatment and directions for future research are discussed.
Asunto(s)
Cannabinoides/farmacología , Cannabinoides/orina , Cannabis/química , Trastornos Relacionados con Cocaína/orina , Cocaína/farmacología , Cocaína/orina , Abuso de Marihuana/orina , Extractos Vegetales/farmacología , Extractos Vegetales/orina , Sueño/efectos de los fármacos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Sueño-Vigilia , Detección de Abuso de Sustancias/métodos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Recently, several countries authorized the use of cannabis flowering tops (dried inflorescences) with a standardized amount of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD) and their acidic precursors [Δ-9-tetrahydrocannabinolic acid A (THCA-A) and cannabidiolic acid (CBDA)] to treat neurogenic pain. We studied the acute pharmacological effects and disposition of cannabinoids and their metabolites in serum, oral fluid, sweat patch and urine of 13 healthy individuals treated with medical cannabis decoction and oil. Cannabinoids and their metabolites were quantified by ultrahigh performance tandem mass spectrometry. Even if the oil contained a significantly higher amount of THC, the absorption of THC and its metabolites were similar in both herbal preparations. Conversely, whereas oil contained a significantly higher amount of CBD and a lower amount of CBDA, absorption was significantly higher after decoction intake. Only cannabinoids present in both herbal preparations (THC, CBD, THCA-A and CBDA) were found in oral fluid, due to the higher acidity compared with that of serum. THC metabolites urinary excretion was always higher after decoction administration. Decoction induced greater feeling of hunger and drowsiness than oil preparation. Pharmacokinetics of cannabinoids, their precursors and their metabolites in biological fluids of individuals treated with cannabis decoction and oil showed a high interindividual variability. The aqueous preparation was generally better absorbed than the oil, even if it contained a minor amount of THC, THCA-A and CBD.
Asunto(s)
Cannabinoides/uso terapéutico , Cannabis/química , Marihuana Medicinal , Preparaciones Farmacéuticas/química , Sudor/química , Adulto , Cannabinoides/farmacología , Femenino , Humanos , Masculino , Marihuana Medicinal/sangre , Marihuana Medicinal/farmacología , Marihuana Medicinal/uso terapéutico , Marihuana Medicinal/orina , Extractos Vegetales/sangre , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/orina , Adulto JovenRESUMEN
Atractylodis rhizoma is a frequently-used traditional Chinese medicine in clinical practice, which have the effect of eliminating dampness and tonifying spleen. And after being processed with wheat bran, the dryness of A. rhizoma is reduced, and the function of tonifying spleen is enhanced. Atractylenolides are the major bioactive components of A. rhizoma, including atractylenolide I (AI), atractylenolide â ¡ (Aâ ¡) and atractylenolide â ¢ (Aâ ¢). The present study aimed to develope a new UPLC-MS/MS method for simultaneous quantification of three atractylenolides in rat urine, and applied to the excretory kinetics in Sprague-Dawley rats after oral administration of crude and processed A. rhizoma extracts. Analytes and internal standard were detected without interference in the multiple reaction monitoring (MRM) mode with positive electrospray ionization. The excretory kinetics parameters were calculated by a urine drug analysis model of drug and statistics (DAS) 3.2.8 software. The t1/2 and Ke of three atractylenolides had no significant difference between crude and processed A. rhizoma, but the recovery accumulative excretion of them in processed A. rhizoma were apparently higher than the crude ones (p<0.05, p<0.01). The results showed that only a small amount of atractylenolides excreted in urine and processing A. rhizoma with wheat bran by stir frying could promote the urinary excretion of them.
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Atractylodes , Cromatografía Liquida , Lactonas/orina , Extractos Vegetales/orina , Eliminación Renal , Sesquiterpenos/orina , Espectrometría de Masas en Tándem , Administración Oral , Animales , Atractylodes/química , Lactonas/administración & dosificación , Lactonas/aislamiento & purificación , Lactonas/farmacocinética , Masculino , Modelos Biológicos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacocinética , Ratas Sprague-Dawley , Rizoma , Sesquiterpenos/administración & dosificación , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacocinéticaRESUMEN
Nobiletin, one of the prevalent polymethoxyflavones in citrus peels, was reported to possess various health benefits. We conducted the excretion study and pharmacokinetics study of nobiletin via oral administration and intravenous injection and 15 day consecutive dosing study using the high fat diet-induced obese rats and their lean counterparts. By comparing the demethylated metabolite profiles in the urine and feces, gut microbiota demonstrated greater biotransformation activity on nobiletin than the host. The absolute oral bioavailability of nobiletin in lean (22.37% ± 4.52%) and obese (18.67% ± 4.80%) rats has a negligible statistically significant difference (P > 0.05). However, a higher extent of demethylated metabolites was found in the feces and plasma of obese rats than lean rats (P < 0.05). Moreover, the consecutive dosing of nobiletin might lead to a higher extent of demethylated metabolites in the plasma and in feces. These results suggested that gut microbiota played important roles in nobiletin metabolism.
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Flavonas/metabolismo , Obesidad/tratamiento farmacológico , Extractos Vegetales/metabolismo , Animales , Disponibilidad Biológica , Biotransformación , Citrus/química , Heces/química , Flavonas/administración & dosificación , Flavonas/sangre , Flavonas/orina , Microbioma Gastrointestinal , Humanos , Masculino , Obesidad/sangre , Obesidad/microbiología , Obesidad/orina , Extractos Vegetales/administración & dosificación , Extractos Vegetales/sangre , Extractos Vegetales/orina , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVES: This study was designed to profile the chemical information of Forsythiae Fructus (FF) and investigate the in-vivo FF-related xenobiotics, especially for lignans. METHODS: Rats were oral administrated of FF and pinoresinol-4-O-glucoside, respectively. Blood and urine samples were collected after ingestion, and xenobiotics was profiled by an UPLC/Qtof MS method. KEY FINDINGS: A total of 19 lignans were identified or tentatively characterized in FF, and 63 lignan-related xenobiotics were found in rat plasma and urine after ingestion of FF. It was found that lignans could be transformed into metabolites by furan ring opening, hydrogenation, demethylation, dehydration and phase II reactions (sulfation and glucuronidation). The whole metabolic behaviour of bisepoxylignan was revealed by evaluating the metabolism of pinoresinol-4-O-glucoside in vivo. It was found that the configuration of C-8/C-8' was retained after furan ring opening and metabolic reactions always occurred at position of C-3/C-4/C-5 or C-3'/C-4'/C-5'. Additionally, other types components in FF and in vivo were also characterized. CONCLUSIONS: This work revealed the in-vivo metabolism of FF, and reported the characteristic metabolic reactions of lignans for the first time. It was also provided the foundation for the further investigation on pharmacodynamic components of FF or TCMs containing FF.
Asunto(s)
Cromatografía Liquida , Forsythia , Lignina/farmacocinética , Extractos Vegetales/farmacocinética , Espectrometría de Masa por Ionización de Electrospray , Administración Oral , Animales , Biotransformación , Forsythia/química , Lignina/sangre , Lignina/aislamiento & purificación , Lignina/orina , Masculino , Extractos Vegetales/sangre , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/orina , Ratas Sprague-DawleyRESUMEN
This research aims to study the antioxidation and anticholinesterase activities of 7'-ethoxy-trans-feruloyltyramine (ETFT), which was an alkaloid isolated from Portulaca oleracea for the first time. Furthermore, its main metabolites and metabolic pathways in rats were also explored. The antioxidation and anticholinesterase effects of ETFT were, respectively, examined using 1,1-diphenyl-2-picrylhydrazyl assay and modified Ellman's method. The results showed that ETFT exhibited both the good antioxidant and anticholinesterase effects. Its main metabolites in rats were implemented, and nine metabolites were finally found in the rat's plasma and urine, including the oxidation, reduction, hydrolysis, glucuronidation, sulfation, and glutathionylation process.
Asunto(s)
Antioxidantes/farmacología , Inhibidores de la Colinesterasa/farmacología , Cromatografía Líquida de Alta Presión , Extractos Vegetales/farmacología , Portulaca , Espectrometría de Masa por Ionización de Electrospray , Tiramina/farmacología , Administración Intravenosa , Animales , Antioxidantes/metabolismo , Biotransformación , Inhibidores de la Colinesterasa/sangre , Inhibidores de la Colinesterasa/orina , Masculino , Extractos Vegetales/sangre , Extractos Vegetales/orina , Ratas Sprague-Dawley , Tiramina/análogos & derivados , Tiramina/sangre , Tiramina/metabolismo , Tiramina/orinaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is an ancient food and medicinal plant. Liquiritigenin and liquiritin, two kinds of major flavonoes in licorice, are effective substances used as antioxidant, anti-inflammatory and tumor-suppressive food, cosmetics or medicines. However, their in vivo metabolites have not been fully explored. AIM OF STUDY: To clarify the metabolism of liquiritigenin and liquiritin in mice. MATERIALS AND METHODS: In this study, we developed a liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry approach to determine the metabolites in mice plasma, bile, urine and feces after oral administration of liquiritigenin or liquiritin. The structures of those metabolites were tentatively identified according to their fragment pathways, accurate masses, characteristic product ions, metabolism laws or reference standard matching. RESULTS: A total of 26 and 24 metabolites of liquiritigenin or liquiritin were respectively identified. The products related with apigenin, luteolin or quercetin were the major metabolites of liquiritigenin or liquiritin in mice. Seven main metabolic pathways including (de)hydrogenation, (de)hydroxylation, (de)glycosylation, (de)methoxylation, acetylation, glucuronidation and sulfation were summarized to tentatively explain their biotransformation. CONCLUSION: This study not only can provide the evidence for in vivo metabolites and pharmacokinetic mechanism of liquiritigenin and liquiritin, but also may lay the foundation for further development and utilization of liquiritigenin, liquiritin and then licorice.
Asunto(s)
Flavanonas/administración & dosificación , Glucósidos/administración & dosificación , Glycyrrhiza , Metabolómica , Extractos Vegetales/administración & dosificación , Administración Oral , Animales , Bilis/metabolismo , Biotransformación , Cromatografía Líquida de Alta Presión , Vías de Eliminación de Fármacos , Heces/química , Flavanonas/sangre , Flavanonas/aislamiento & purificación , Flavanonas/orina , Glucósidos/sangre , Glucósidos/aislamiento & purificación , Glucósidos/orina , Glycyrrhiza/química , Masculino , Ratones Endogámicos C57BL , Extractos Vegetales/sangre , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/orina , Espectrometría de Masas en TándemRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Extracts from Cranberry fruits (Vaccinium macrocarpon) are traditionally used against urinary tract infections, mainly due to antiadhesive activity against uropathogenic E. coli (UPEC), but the exact mode of action and compounds, responsible for the activity, are unknown. AIM OF THE STUDY: i. To investigate if cranberry extract acts only by a single component or must be assessed as a multi-active-compound preparation; ii to screen isolated cranberry-related natural products under in vitro conditions to pinpoint natural products with antiadhesive effects against UPEC, followed by in silico calculations (QSAR) to predict potential antiadhesive compounds; iii. investigations by using urine samples from cranberry treated volunteers for evaluation on the bacterial transcriptome and the mannose-binding side of FimH, iv. to investigate if besides Tamm Horsfall Protein induction in the kidney, the extract acts also directly against UPEC. MATERIAL AND METHODS: Antiadhesive activity of 105 compounds was determined by flow cytometric adhesion assay (UPEC UTI89 on T24 bladder cells). Urine samples from 16 volunteers treated with cranberry extract (p.o., 7 days, 900 mg/day) were used for ex vivo testing concerning influence on the bacterial transcriptome (Illumina RNA-seq) and interaction with the mannose binding domain of type-1 fimbriae. RESULTS: i. The antiadhesive effect of cranberry extract cannot be attributed to a single compound or to a single fraction. ii. Unglycosylated flavones and flavonols with bulky substitution of the B ring contribute to the antiadhesive activity. 3'-8â³-biflavones and flavolignans (not related to cranberry fruits) were identified as potent antiadhesive compounds against UPEC. iii. QSAR yielded a model with good statistical performance and sufficient internal and external predictive ability. iv. Urine samples from male cranberry-treated volunteers indicated significant interaction with the mannose binding domain of type-1 fimbriae, which correlated with the amount of Tamm-Horsfall Protein in the test samples. v Cranberry extract did not influence the UPEC transcriptome; gene expression of bacterial adhesins (P-, S-fimbrae, curli) was not influenced by the urine samples, while a slight, but non-significant upregulation of type 1 fimbriae was observed. CONCLUSIONS: B-ring substituted flavones and flavonols from cranberry contribute to the antiadhesive activity against UPEC by inhibition of the FimH-mediated interaction with the host cell bladder epithelium.
Asunto(s)
Antibacterianos/farmacología , Adhesión Bacteriana/efectos de los fármacos , Infecciones por Escherichia coli/tratamiento farmacológico , Extractos Vegetales/farmacología , Infecciones Urinarias/tratamiento farmacológico , Escherichia coli Uropatógena/efectos de los fármacos , Vaccinium macrocarpon , Adhesinas de Escherichia coli/genética , Adhesinas de Escherichia coli/metabolismo , Administración Oral , Adulto , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Antibacterianos/aislamiento & purificación , Antibacterianos/orina , Línea Celular , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/orina , Femenino , Proteínas Fimbrias/genética , Proteínas Fimbrias/metabolismo , Frutas , Regulación Bacteriana de la Expresión Génica , Interacciones Huésped-Patógeno , Humanos , Masculino , Persona de Mediana Edad , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/orina , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/microbiología , Infecciones Urinarias/microbiología , Infecciones Urinarias/orina , Orina/microbiología , Uromodulina/metabolismo , Escherichia coli Uropatógena/genética , Escherichia coli Uropatógena/patogenicidad , Urotelio/efectos de los fármacos , Urotelio/microbiología , Vaccinium macrocarpon/química , Adulto JovenRESUMEN
Mitragyna speciosa (Kratom) has emerged as a recreational drug and a substance of medicinal intrigue. Although the drug was initially used recreationally for its sedating and euphoric effects, more recently its use has been associated with the non-medically supervised treatment of opioid abstinence syndrome. Mitragynine is the principal pharmacologically active alkaloid in kratom. Although metabolites of mitragynine have been identified, the cytochrome P450 (CYP450) enzymes responsible for its biotransformation are still under investigation. The goal of this study was to contribute further knowledge regarding CYP450 activity as it relates to mitragynine. Recombinant cytochrome P450 enzymes (rCYPs) were used to investigate the isoforms involved in its metabolism. Biotransformational products were identified using liquid chromatography-quadrupole/time of flight-mass spectrometry. Four rCYP enzymes (2C18, 2C19, 2D6 and 3A4) were found to contribute to the metabolism of mitragynine. 7-Hydroxymitragynine (which has an affinity for the mu-opioid receptor >10-folds that of morphine) was produced exclusively by 3A4. 9-O-demethylmitragynine, the most abundant metabolite in vitro (and the most prevalent metabolite in urine among kratom users) was produced by 2C19, 3A4 and 2D6. 16-Carboxymitragynine was produced by rCYPs 2D6, 2C19 and 2C18. 2C19 was solely responsible for the formation of 9-O-demethyl-16-carboxymitragynine. In vitro rCYP studies were compared with phase I metabolites in urine from cases involving mitragynine.
Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Mitragyna , Extractos Vegetales/orina , Alcaloides de Triptamina Secologanina/orina , Cromatografía Liquida , Humanos , Oxidación-Reducción , Espectrometría de Masas en TándemRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Herbal medicine contains hundreds of natural products, and studying their absorption, metabolism, distribution, and elimination presents great challenges. Gelsemium elegans (G. elegans) is a flowering plants in the Loganiaceae family. The plant is known to be toxic and has been used for many years as a traditional Chinese herbal medicine for the treatment of rheumatoid arthritis, neuropathic pain, spasticity, skin ulcers and cancer. It was also used as veterinary drugs for deworming, promoting animal growth, and pesticides. At present, studies on the metabolism of G. elegans have primarily focused on only a few single available reference ingredients, such as koumine, gelsemine and gelsedine. MATERIAL AND METHODS: The goal of this work is to elucidate the overall metabolism of whole G. elegans powder in goats using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC/QqTOF-MS). RESULTS: Analyses of plasma, urine and fecal samples identified or tentatively characterized a total of 44 absorbed natural products and 27 related produced metabolites. Gelsedine-type, sarpagine-type and gelsemine-type alkaloids were the compounds with the highest metabolite formation. In the present study, most natural products identified in G. elegans were metabolized through glucuronidation and oxidation. Hydrogenation, dehydrogenation and demethylation also occurred. CONCLUSION: To our knowledge, this is the first report of the metabolite profiling of the G. elegans crude extract in goats, which is of great significance for a safer and more rational application of this herbal medicine.
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Gelsemium , Extractos Vegetales/farmacocinética , Animales , Cromatografía Líquida de Alta Presión , Heces/química , Cabras , Absorción Intestinal , Masculino , Espectrometría de Masas , Medicina Tradicional China , Extractos Vegetales/sangre , Extractos Vegetales/orinaRESUMEN
The aim of this work was to profile, by using an HPLC-MS/MS method, cranberry compounds and metabolites found in human urine after ingestion of a highly standardized cranberry extract (Anthocran®). Two different strategies were adopted for the data analysis: a targeted and an untargeted approach. These strategies allowed the identification of 42 analytes including cranberry components, known metabolites and metabolites hitherto unreported in the literature, including six valerolactones/valeric acid derivatives whose presence in urine after cranberry consumption has never been described before. Absolute concentrations of 26 over 42 metabolites were obtained by using pure available standards. Urine collected at different time points after the last dosage of Anthocran® were tested on the reference strain C. albicans SC5314, a biofilm-forming strain. Fractions collected after 12 h were found to significantly reduce the adhesion and biofilm formation compared to the control (p < 0.05). A similar effect was then obtained by using Anthocran™ Phytosome™, the lecithin formulation containing 1/3 of standardized cranberry extract and formulated to enhance the absorption of the cranberry components. The urinary profile of cranberry components and metabolites in the urine fractions collected at 1 h, 6 h and 12 h after the last capsule intake were then reproduced by using the pure standards at the concentration ranges found in the urine fraction, and tested on C. albicans. Only the mixture mimicking the urinary fraction collected at 12 h and containing as main components, quercetin and 5-(3',4'-dihydroxyphenyl)-γ-valerolactone was found effective thus confirming the ex-vivo results.
Asunto(s)
Biopelículas/efectos de los fármacos , Candida albicans/efectos de los fármacos , Lactonas/farmacología , Ácidos Pentanoicos/farmacología , Extractos Vegetales/orina , Vaccinium macrocarpon/química , Adulto , Antocianinas/orina , Biopelículas/crecimiento & desarrollo , Candida albicans/fisiología , Cromatografía Líquida de Alta Presión/métodos , Femenino , Flavonoides/orina , Humanos , Hidroxibenzoatos/orina , Lactonas/química , Lactonas/orina , Espectrometría de Masas/métodos , Ácidos Pentanoicos/química , Ácidos Pentanoicos/orina , Extractos Vegetales/administración & dosificación , Extractos Vegetales/metabolismo , Polifenoles/clasificación , Polifenoles/orina , Adulto JovenRESUMEN
Fucoidans are a group of homo-and hetero-polysaccharides, which necessarily contains residues of sulfated α-L-fucose. Fucoidans are found only in brown algae. These polysaccharides exhibit a wide spectrum of biological activity and have a great therapeutic potential. Enzymes capable of catalyzing the degradation of fucoidans are absent in the mammalian enzyme system. The question arises: is the transformation of fucoidan in mammals, particularly in human possible? Studies in vivo (in situ) and in vitro have demonstrated that high molecular weight fucoidans are absorbed across rat intestinal epithelial cells, accumulated by liver macrophages, and characterized by low levels in blood and urine. Using the example of the Okinawa Prefecture (Japan) residents, it was shown that Cladosiphon okamuranus alga is digested and the fucoidan contained in this alga is absorbed in the human body.
Asunto(s)
Phaeophyceae/química , Extractos Vegetales/química , Extractos Vegetales/metabolismo , Polisacáridos/química , Polisacáridos/metabolismo , Animales , Células Epiteliales/efectos de los fármacos , Microbioma Gastrointestinal/genética , Humanos , Absorción Intestinal , Hígado , Macrófagos , Metaboloma , Peso Molecular , Extractos Vegetales/sangre , Extractos Vegetales/orina , Polisacáridos/sangre , Polisacáridos/orinaRESUMEN
Increased processing of pulses generates large volumes of hulls, which are known as an excellent source of phenolic antioxidants. However, the bioavailability and in vivo activity of these phenolics are rarely reported. This research was therefore carried out to study the absorption, metabolism, and in vivo antioxidant activities of green pea hull (GPH) phenolics using ultrahigh-pressure liquid chromatography with a linear ion trap-high-resolution Orbitrap mass spectrometry and an oxidative stress rat model. A total of 31 phenolics, including 4 phenolic acids, 24 flavonoids, and 3 other phenolics, were tentatively identified. Ten of these phenolics and 49 metabolites were found in the plasma and urine of rats, which helped to explain the favorable changes by GPH phenolics in key antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and glutathione) and indicators (total antioxidant capacity, malondialdehyde) in the plasma and different tissues of rats. This is the first comprehensive report on dry pea hull phenolics and their bioavailability, metabolic profiles, and mechanisms of in vivo antioxidant activities.
Asunto(s)
Antioxidantes/metabolismo , Fenoles/sangre , Fenoles/orina , Pisum sativum/metabolismo , Extractos Vegetales/sangre , Extractos Vegetales/orina , Residuos/análisis , Animales , Antioxidantes/química , Disponibilidad Biológica , Femenino , Flavonoides/sangre , Flavonoides/metabolismo , Flavonoides/orina , Hidroxibenzoatos/sangre , Hidroxibenzoatos/metabolismo , Hidroxibenzoatos/orina , Estructura Molecular , Pisum sativum/química , Fenoles/química , Extractos Vegetales/química , Ratas , Ratas Sprague-DawleyRESUMEN
A cross-over study was conducted in 16 healthy adult volunteers to describe the urinary excretion of polyphenols from date seeds and investigate the antioxidant effect after consumption of different doses of date seeds powder (DSP), bread (DSB) and extract (DSE). After 12 h of fasting, one of the six treatments (0.25 g and 0.5 g/kg bodyweight DSP, 360 g of 10% and 15% DSB, 30 mg and 60 mg/kg bodyweight DSE) was provided along with breakfast, with a two weeks wash-out period between 2 consecutive treatments. Blood was drawn at baseline, 1, 2, 8 and 24 h post intake. Urine was collected at baseline, 3, 8, and 24 h post intake. An abundant release of polyphenols was detected in urine within the 0-3 h post intake, reached a peak at 8 h, then decreased with polyphenols still being detected up to 24 h post intake. The antioxidant defence system, as measured by reduced glutathione (GSH), was strengthened as soon as 1 h and up to 8 h post intake. Markers of protein and lipid oxidative damages were reduced from 1 h and up to 8 and 24 h post intake, respectively. This supports an antioxidant effect of date seeds products in humans, most probably due to their polyphenols.
Asunto(s)
Antioxidantes/administración & dosificación , Suplementos Dietéticos , Estrés Oxidativo/efectos de los fármacos , Phoeniceae/química , Extractos Vegetales/administración & dosificación , Polifenoles/administración & dosificación , Semillas/química , Administración Oral , Adolescente , Adulto , Antioxidantes/aislamiento & purificación , Antioxidantes/metabolismo , Biomarcadores/sangre , Biomarcadores/orina , Estudios Cruzados , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/orina , Polifenoles/aislamiento & purificación , Polifenoles/orina , Polvos , Factores de Tiempo , Emiratos Árabes Unidos , Adulto JovenRESUMEN
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.
Asunto(s)
Alcaloides , Benzodioxoles , Piperidinas , Extractos Vegetales , Alcamidas Poliinsaturadas , Estilbenos , Administración Intravenosa , Administración Oral , Alcaloides/administración & dosificación , Alcaloides/sangre , Alcaloides/farmacocinética , Alcaloides/orina , Animales , Artocarpus , Benzodioxoles/administración & dosificación , Benzodioxoles/sangre , Benzodioxoles/farmacocinética , Benzodioxoles/orina , Interacciones Farmacológicas , Masculino , Piperidinas/administración & dosificación , Piperidinas/sangre , Piperidinas/farmacocinética , Piperidinas/orina , Extractos Vegetales/administración & dosificación , Extractos Vegetales/sangre , Extractos Vegetales/farmacocinética , Extractos Vegetales/orina , Alcamidas Poliinsaturadas/administración & dosificación , Alcamidas Poliinsaturadas/sangre , Alcamidas Poliinsaturadas/farmacocinética , Alcamidas Poliinsaturadas/orina , Ratas , Ratas Wistar , Estilbenos/administración & dosificación , Estilbenos/sangre , Estilbenos/farmacocinética , Estilbenos/orinaRESUMEN
The dominant anthocyanins in blackcurrant are delphinidin-3-O-rutinoside and cyanidin-3-O-rutinoside. Data on their absorption and distribution in the human body are limited. Therefore, we performed a human pilot study on five healthy male volunteers consuming a blackcurrant ( Ribes nigrum L.) extract. The rutinosides and their degradation products gallic acid and protocatechuic acid were determined in plasma and urine. The rutinosides' concentrations peaked in both plasma and urine samples within 2 h of extract ingestion. The recoveries of delphinidin-3-O-rutinoside and cyanidin-3-O-rutinoside from urine samples were 0.040 ± 0.011% and 0.048 ± 0.016%, respectively, over a 48 h period. Protocatechuic acid concentration increased significantly after ingestion of the blackcurrant extract. Our results show that after ingestion of a blackcurrant extract containing delphinidin-3-O-rutinoside and cyanidin-3-O-rutinoside, significant quantities of biologically active compounds circulated in the plasma and were excreted via urine. Furthermore, these results contribute to the understanding of anthocyanin metabolism in humans.
Asunto(s)
Antocianinas/sangre , Antocianinas/orina , Ribes/metabolismo , Adulto , Antocianinas/química , Cromatografía Líquida de Alta Presión , Humanos , Masculino , Espectrometría de Masas , Proyectos Piloto , Extractos Vegetales/sangre , Extractos Vegetales/química , Extractos Vegetales/orina , Ribes/química , Adulto JovenRESUMEN
Three silica hydride based novel chromatographic phases chemically-bonded with allyloxy-DL-alpha-tocopherol, allylpentafluorophenyl, and 1-eicosene moieties were evaluated as separation media for selected phytocannabinoids and other substances of abuse. In order to assess column selectivity, a series of reference standards was analyzed and detected by using liquid chromatography with mass spectrometry. Further, quantitative detections of cannabidiol and tetrahydrocannabinol were attempted for the extracts of cannabis plants and cannabidiol gummy formulation. For potential bioanalytical applications, the columns were evaluated for substance screening in a human urine matrix. In summary, the newly developed columns are functional and effective for the analysis of phytocannabinoids and various psychoactive drugs with or without the presence of biological matrices.
Asunto(s)
Cannabinoides/análisis , Cannabinoides/orina , Cromatografía Líquida de Alta Presión/métodos , Extractos Vegetales/análisis , Psicotrópicos/análisis , Psicotrópicos/orina , Silicatos/química , Cromatografía Líquida de Alta Presión/instrumentación , Dronabinol/análisis , Dronabinol/orina , Humanos , Extractos Vegetales/orinaRESUMEN
BACKGROUND: Ayahausca is an ethnobotanical drink of South America and the compound dimethyltryptamine (DMT) is primarily responsible for the hallucinogenic effects. DMT has a short half-life and its detection in urinary drug screens is challenging. We investigate a simple alternate approach to detect ayahuasca consumption by relying on other constituents of the drink, the ß-carboline harmala alkaloids. METHODS: Three commercially sourced harmala alkaloids were characterized and added to a non-targeted high-resolution mass spectrometry urine drug screening method. All analyses were performed on a Waters Xevo G2-XS LC-QTof, in positive electrospray ionization mode. The mass detector was operated in MSE mode and data processed with UNIFI™ software. A urine specimen from a patient suspected to have consumed ayahuasca was analyzed by a non-targeted drug screen. RESULTS: The harmala alkaloids: harmine, harmaline and tetrohydroharmaline (THH) were characterized and their detection data added to the toxicology screening library. Harmaline and THH were detected in the patient's urine specimen. CONCLUSION: The inclusion of the harmala alkaloids into the drug screen method library may enable the detection of ayahuasca use in patients that undergo non-targeted drug screen.