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1.
Biomed Chromatogr ; 36(2): e5253, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34596250

RESUMO

Saururus chinensis (SC) possesses significant anti-diabetic activity and lignans were its major bioactive compounds. In this study, a rapid and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was established for simultaneous quantification of six lignans, namely (-)-(7R,8R)-machilin D (1), verrucesin (2), rel-(7S,8S,7'R,8'R)-3,3',4,4',5,5'-hexamethoxy-7.O.7',8.8'-lignan (3), manassantin A (4), manassantin B (5), and saucerneol F (6) in rat's plasma. It was validated with acceptable linearity (r ≥ 0.9922), accuracy (80.42-95.17%), precision (RSD ≤ 12.08%), and extraction recovery (80.36-93.45%). The method was successfully applied to the comparative pharmacokinetic study of the six lignans in normal and diabetic rats after oral administration of SC extract. Results showed that the areas under the plasma concentration-time curve (AUC0 → t and AUC0 → ∞ ) of (-)-(7R,8R)-machilin D, rel-(7S,8S,7'R,8'R)-3,3',4,4',5,5'-hexamethoxy-7.O.7',8.8'-lignan, manassantin B, and saucerneol F in diabetic rats were significantly increased, and the plasma clearance (CL) of (-)-(7R,8R)-machilin D in diabetic rats was significantly decreased. However, the AUC0 → t and AUC0 → ∞ of verrucesin were significantly decreased, and its CL was significantly increased in diabetic rats compared with those in normal rats. These results indicated that there were remarkable differences in the pharmacokinetic parameters between the normal and diabetic rats. The pharmacokinetic studies might be beneficial for the clinical use of SC as hypoglycemic agent.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Lignanas , Extratos Vegetais , Saururaceae/química , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão/métodos , Lignanas/sangue , Lignanas/química , Lignanas/farmacocinética , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacocinética , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodos
2.
BMC Vet Res ; 17(1): 275, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34399756

RESUMO

BACKGROUND: Myrislignan is a natural product from Myristica sp. with diverse pharmacological activities. Recently, the anti-Toxoplasma gondii (T. gondii) activity of myrislignan has been proposed, and in vivo studies of its pharmacokinetics in BALB/c mice are necessary to further evaluate the clinical effects of myrislignan. RESULTS: In this study, a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to quantify myrislignan levels in mouse plasma using dehydrodiisoeugenol as an internal standard (IS) in positive ion mode. Chromatographic separation of the analytes was achieved using an ACE Ultracore Super C18 analytical column (2.5 µm, 2.1 × 50 mm) at 30 °C. A gradient mobile phase consisting of water (0.1 % formic acid) and acetonitrile (0.1 % formic acid) was delivered at a flow rate of 0.4 mL/min. Myrislignan and the IS eluted at 1.42 and 1.71 min, respectively. A good excellent linear response across the concentration range of 1-1000 ng/mL was achieved (r2 = 0.9973). The lower limit of quantification (LLOQ) was 1 ng/mL, and the inter- and intra-day accuracy and precision of the method showed relative standard deviations (RSDs) less than 10 %. The method was applied to examine the pharmacokinetics of myrislignan in mouse plasma following a single oral administration of 200 mg/kg or intraperitoneal administration of 50 mg/kg myrislignan, and the bioavailability (F) of orally administered myrislignan was only 1.97 % of the bioavailability of intraperitoneally administered myrislignan. CONCLUSIONS: A rapid and sensitive LC-MS/MS method has been was developed, validated and successfully used to determine myrislignan levels in mice after oral or intraperitoneal administration. This study is the first to report the pharmacokinetic parameters of myrislignan in mice and to compare its pharmacokinetics after oral and intraperitoneal administration, which will be useful for further research on the administration of myrislignan in animals and humans.


Assuntos
Cromatografia Líquida , Lignanas/sangue , Lignanas/farmacocinética , Espectrometria de Massas em Tandem , Administração Oral , Animais , Área Sob a Curva , Células 3T3 BALB , Disponibilidade Biológica , Meia-Vida , Injeções Intraperitoneais/veterinária , Lignanas/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
3.
J Sep Sci ; 44(7): 1299-1306, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33387366

RESUMO

Arctigenin is a natural lignin and a main active component of Fructus arctii, the dried fruit of Arctium lappa. This compound was reported to have some biological activities such as anti-inflammatory, antioxidant, antiviral, renoprotective, and antitumor effects. Arctigenin is mainly metabolized to arctigenin-4'-O-glucuronide by UDP-glucuronosyltransferase. In this study, a simultaneous quantification method was established and validated for measuring arctigenin and arctigenin-4'-O-glucuronide in mouse plasma using ultra-high performance liquid chromatography with tandem mass spectrometry. The assay fulfilled the requirements of the United States Food and Drug Administration guideline for assay validation, with a lower limit of quantification of 2.00 ng/mL for arctigenin and 50.0 ng/mL for arctigenin-4'-O-glucuronide. The recovery rate and matrix effect ranged from 78.4 to 102.8% and 92.5 to 106.3%, respectively, for arctigenin, and 74.3 to 109.2% and 94.9 to 110.2% for arctigenin-4'-O-glucuronide. The method was applied to the measurement of plasma concentrations of arctigenin and arctigenin-4'-O-glucuronide in the plasma of mice after administration of arctigenin. All measured concentrations were within the calibration ranges. Our novel method may be useful to measure plasma arctigenin and arctigenin-4'-O-glucuronide concentrations, and contribute to evaluate the pharmacokinetics of arctigenin and arctigenin-4'-O-glucuronide in mice.


Assuntos
Furanos/sangue , Glucuronídeos/sangue , Lignanas/sangue , Animais , Cromatografia Líquida de Alta Pressão , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Espectrometria de Massas em Tandem
4.
J Sep Sci ; 44(3): 717-725, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33247873

RESUMO

Schisandrin B has been proved to possess anti-inflammatory and anti-endoplasmic effects, could improve cardiac function, inhibit apoptosis, and reduce inflammation after ischemic injury. However, the detailed metabolic mechanism and potential pathways of Schisandrin B effects on myocardial injury are unclear. Metabolomics could yield in-depth mechanistic insights and explore the potential therapeutic effect of natural products. In this study, the preparation of doxorubicin-induced myocardial injury rat model for evaluation of Schisandrin B on viral myocarditis sequelae related pathological changes and its mechanism. The metabolite profiling of myocardial injury rats was performed through ultra-high performance liquid chromatography combined with mass spectrometry combined with pattern recognition approaches and pathway analysis. A total of 15 metabolites (nine in positive ion mode and six in negative ion mode) were considered as potential biomarkers of myocardial injury, and these metabolites may correlate with the regulation of Schisandrin B treatment. A total of six metabolic pathways are closely related to Schisandrin B treatment, including glycerophospholipid metabolism, sphingolipid metabolism, purine metabolism, etc. This study revealed the potential biomarkers and metabolic network pathways of myocardial injury, and illuminated the protective mechanism of Schisandrin B on myocardial injury.


Assuntos
Lignanas/metabolismo , Metabolômica , Miocárdio/química , Compostos Policíclicos/metabolismo , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Cromatografia Líquida de Alta Pressão , Ciclo-Octanos/sangue , Ciclo-Octanos/metabolismo , Modelos Animais de Doenças , Lignanas/sangue , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Compostos Policíclicos/sangue , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem
5.
J Dairy Sci ; 104(1): 391-396, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33189295

RESUMO

Mammalian lignans are phytoestrogens with important bioactivities, and their concentrations in livestock milk may influence the health of consumers. This research aimed to establish a method to quantify multiple mammalian lignans in the biofluids of dairy sheep using ultra-HPLC-triple quadropole mass spectrometry with multiple-reaction monitoring. Secoisolariciresinol, 2-[(4-hydroxy-3-methoxyphenyl)methyl]-3-[(3-hydroxyphenyl)methyl]-1,4-butanediol, enterodiol (ED), enterolactone (EL), ED-sulfate (ED-S), and EL-sulfate (EL-S) were purified from the urine of flaxseed cake-fed dairy sheep. The structures of these lignans were identified by a combination of mass and nuclear magnetic resonance spectra. These purified lignans were used as standards to optimize their quantification conditions in urine, milk, and plasma of dairy sheep. On this basis, the lignan metabolites in biofluids were quantified. To improve analysis sensitivity, plasma and milk were pretreated with acetonitrile containing 1% formic acid and passed through a HybridSPE-PL 55261-U column (Supelco, Bellefonte, PA). The limit of quantification of the lignans ranged from 1.43 to 18.3 ng/mL in plasma, and from 1.01 to 18.7 ng/mL in milk. The linearity of the calibration curves ranged from their limit of quantification to at least 217 ng/mL in plasma, and 217 ng/mL in milk. Regression coefficient of the calibration curves were above 0.99 for secoisolariciresinol, 2-[(4-hydroxy-3-methoxyphenyl)methyl]-3-[(3-hydroxyphenyl)methyl]-1,4-butanediol, ED, EL, ED-S, and EL-S, indicating satisfactory relationships between the peak areas and concentrations in the quantification range. The relative concentrations of ED-glucuronide and EL-glucuronide (EL-G) in different biofluids were compared based on their chromatogram peak areas. The sheep plasma contained all forms of mammalian lignans (i.e., ED, EL, ED-S, EL-S, ED-glucuronide, and EL-G.); the urine contained ED, EL, ED-S, and EL-S; and the milk contained ED, EL, ED-S, EL-S, and EL-G. Milk-to-plasma concentration ratios of the mammalian lignans indicated that the free forms were more permeable than the sulfated conjugates. Mammalian lignans found in sheep plasma and milk may provide health benefits to the sheep and sheep-product consumers. The analytical method established in this work could be used to quantify mammalian lignans in livestock products.


Assuntos
Ração Animal , Linho , Lignanas/análise , Leite/química , Ovinos , 4-Butirolactona/análogos & derivados , 4-Butirolactona/metabolismo , Animais , Butileno Glicóis/metabolismo , Linho/química , Glucosídeos/análise , Lignanas/sangue , Lignanas/metabolismo , Lignanas/urina , Sementes/química
6.
Nutr Cancer ; 72(7): 1155-1169, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31617773

RESUMO

Lignans are associated with improved postmenopausal breast cancer (BC) survival, but whether these associations, particularly with enterolactone (major lignan metabolite), persist over time is unclear. Little is known about other phytoestrogens on prognosis in long-term survivors. The study examines associations of prognosis with 1) circulating postdiagnosis enterolactone, 2) eight circulating phytoestrogen metabolites, and 3) changes in enterolactone and genistein. In a German cohort of 2,105 postmenopausal BC patients with blood samples collected at recruitment 2002-2005 (baseline) and re-interview in 2009 (follow-up), delay-entry Cox proportional hazards regression was used. Landmark analysis showed that circulating enterolactone (log2) associations with 5-year survival changed over time, with strongest hazard ratios of 0.89 (95% CI, 0.80-0.99) at blood draw (BD) and 0.86 (0.77-0.97) at 2 years post-BD for BC mortality, and 0.87 (0.80-0.95) at BD and 0.84 (0.76-0.92) at 3 years post-BD for all-cause mortality, which attenuated thereafter. In long-term survivors, increasing concentrations of genistein (1.17, 1.01-1.36), resveratrol (1.19, 1.02-1.40), and luteolin (1.96, 1.07-3.58) measured in follow-up blood samples were associated with poorer subsequent prognosis. Neither enterolactone at follow-up nor changes in enterolactone/genistein were associated with prognosis. Large long-term longitudinal studies with multiple phytoestrogen measurements are required to understand long-term effects of phytoestrogens after BC.


Assuntos
Neoplasias da Mama/sangue , Fitoestrógenos/sangue , Pós-Menopausa/sangue , Sobreviventes , 4-Butirolactona/análogos & derivados , 4-Butirolactona/sangue , Idoso , Biomarcadores Tumorais/sangue , Neoplasias da Mama/mortalidade , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Genisteína/sangue , Alemanha , Humanos , Lignanas/sangue , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Sobrevida
7.
J Sep Sci ; 43(2): 406-417, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31633862

RESUMO

Zhi-Zi-Hou-Po Decoction, consisting of Gardenia jasminoides Ellis, Magnolia officinalis Rehd. et Wils., and Citrus aurantium L, is a classical Traditional Chinese Medicine formula for the treatment of depression. In order to make good and rational use of this formula in the future, a sensitive, selective, and reliable ultra high performance liquid chromatography with tandem mass spectrometry method was developed for simultaneous determination of two iridoid glycosides (geniposide and genipin gentiobioside), two lignans (honokiol and magnolol), four flavonoid glycosides (isonaringin, naringin, hesperidin, and neohesperidin), the major bioactive constituents of Zhi-Zi-Hou-Po Decoction, in rat plasma using paeoniflorin as internal standard. Plasma samples were pretreated by a simple protein precipitation with acetonitrile. Chromatographic separation was performed on a shim-pack XR-ODS C18 column (75 × 3.0 mm, 2.2 µm) using gradient elution with mobile phase consisting of 0.1% formic acid aqueous solution and acetonitrile at a flow rate of 0.5 mL/min. Mass spectrometric detection was conducted on a 3200 QTRAP mass spectrometry equipped with electrospray ionization source in negative ionization mode. Quantification was performed using multiple reactions monitoring mode. Calibration curves exhibited good linearity (r > 0.9947) over a wide concentration range for all analytes, and the lower limits of quantification were 10, 5, 1, 5, 1, 5, 1, and 5 ng/mL for geniposide, genipin gentiobioside, honokiol, magnolol, isonaringin, naringin, hesperidin, and neohesperidin, respectively. The intraday and interday precisions at three quality control levels were less than 12.3% and the accuracies ranged from -11.2 to 10.7%. Extraction recovery, matrix effect, and stability were satisfactory in rat plasma. The validated method was successfully applied to a pharmacokinetic study of the eight analytes after oral administration of Zhi-Zi-Hou-Po decoction to rats.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Flavonoides/farmacocinética , Glicosídeos Iridoides/farmacocinética , Lignanas/farmacocinética , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/análise , Flavonoides/administração & dosagem , Flavonoides/sangue , Glicosídeos Iridoides/administração & dosagem , Glicosídeos Iridoides/sangue , Lignanas/administração & dosagem , Lignanas/sangue , Masculino , Medicina Tradicional Chinesa , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
8.
Diabetologia ; 62(6): 959-969, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30963187

RESUMO

AIMS/HYPOTHESIS: The phytoestrogen enterolactone is a gut microbiota-derived metabolite of plant lignans with suggested beneficial properties for health. In the current study, we investigated the association between pre-diagnostic plasma enterolactone concentrations and mortality among individuals diagnosed with type 2 diabetes. METHODS: In a population of people diagnosed with diabetes, nested within the Danish Diet, Cancer and Health cohort, we conducted a case-cohort study including a random sample of n = 450 cases (deceased) and a randomly selected subcohort of n = 850 (in total n = 617 deaths). Information on diagnosis, vital status and cause of death was obtained from Danish registers. Cox proportional hazard models with special weighting were applied to assess all-cause and cause-specific mortality. RESULTS: The median enterolactone concentration of the current population was low, 10.9 nmol/l (5th percentile to 95th percentile: 1.3-59.6), compared with previously reported concentrations from the Diet, Cancer and Health cohort. Pre-diagnostic enterolactone concentrations were associated with lower all-cause mortality when assessed linearly per doubling in concentration (log2) (HR 0.91 [95% CI 0.85, 0.96]) and according to quartiles (HR 0.63 [95% CI 0.48, 0.84]) for the highest quartile of enterolactone compared with the lowest quartile. For cause-specific mortality, only death from diabetes (registered as underlying cause of death) reached statistical significance. CONCLUSIONS/INTERPRETATION: Based on this large cohort of people with diabetes with detailed and complete baseline and follow-up information, pre-diagnostic enterolactone concentrations were inversely associated with mortality. To our knowledge, this is the first study on enterolactone and type 2 diabetes mortality. Our findings call for further exploration of enterolactone in type 2 diabetes management.


Assuntos
4-Butirolactona/análogos & derivados , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Lignanas/sangue , Lignanas/metabolismo , Neoplasias/metabolismo , 4-Butirolactona/sangue , 4-Butirolactona/metabolismo , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/mortalidade , Neoplasias/patologia , Prognóstico , Distribuição Aleatória
9.
Breast Cancer Res Treat ; 173(3): 545-557, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30367332

RESUMO

PURPOSE: Exposure to the polyphenolic plant lignan secoisolariciresinol diglucoside (SDG) and its metabolite enterolactone (ENL) has been associated with reduced breast cancer progression, particularly for estrogen receptor alpha (ERα)-negative disease, and decreased preclinical mammary tumor growth. However, while preclinical studies have established that SDG and ENL affect measures of progression in models of triple-negative breast cancer (TNBC, a subset of ERα-negative disease), the molecular mechanisms underlying these effects remain unclear. METHODS: C57BL/6 mice were fed a control diet (control, 10% kcal from fat) or control diet + SDG (SDG, 100 mg/kg diet) for 8 weeks, then orthotopically injected with syngeneic E0771 mammary tumor cells (a model of TNBC); tumor growth was monitored for 3 weeks. The role of reduced NF-κB signaling in SDG's anti-tumor effects was explored in vitro via treatment with the bioactive SDG metabolite ENL. In addition to the murine E0771 cells, the in vitro studies utilized MDA-MB-231 and MCF-7 cells, two human cell lines which model the triple-negative and luminal A breast cancer subtypes, respectively. RESULTS: SDG supplementation in the mice significantly reduced tumor volume and expression of phospho-p65 and NF-κB target genes (P < 0.05). Markers of macrophage infiltration were decreased in the distal-to-tumor mammary fat pad of mice supplemented with SDG relative to control mice (P < 0.05). In vitro, ENL treatment inhibited viability, survival, and NF-κB activity and target gene expression in E0771, MDA-MB-231, and MCF-7 cells (P < 0.05). Overexpression of Rela attenuated ENL's inhibition of E0771 cell viability and survival. CONCLUSIONS: SDG reduces tumor growth in the E0771 model of TNBC, likely via a mechanism involving inhibition of NF-κB activity. SDG could serve as a practical and effective adjuvant treatment to reduce recurrence, but greater understanding of its effects is needed to inform the development of more targeted recommendations for its use.


Assuntos
Anti-Inflamatórios/farmacologia , Butileno Glicóis/farmacologia , Linho/química , Glucosídeos/farmacologia , Neoplasias Mamárias Animais/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , 4-Butirolactona/análogos & derivados , 4-Butirolactona/sangue , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Biomarcadores , Butileno Glicóis/administração & dosagem , Butileno Glicóis/química , Linhagem Celular Tumoral , Sobrevivência Celular , Citocinas/sangue , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Perfilação da Expressão Gênica , Glucosídeos/administração & dosagem , Glucosídeos/química , Imuno-Histoquímica , Lignanas/sangue , Neoplasias Mamárias Animais/tratamento farmacológico , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/patologia , Camundongos
10.
Nutr Cancer ; 71(3): 385-398, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30375890

RESUMO

Lignan intake, and its richest food source, flaxseed, have been associated with reduced breast cancer risk. Endogenous sex hormones, such as estrogens, play a role in breast cancer development, and lignans may alter these sex hormone levels. To assess the effect of flaxseed on circulating sex hormones, a randomized controlled trial was conducted among 99 postmenopausal women in Toronto, Canada. The intervention arm consumed 2 tablespoons (15 g) of ground flaxseed daily for 7 weeks; the control arm maintained usual diet. Baseline and week 7 concentrations of 14 serum sex hormones were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and immunoassay, and serum enterolignans (lignan biomarker) using LC-MS/MS. Intervention effects on sex hormone levels were assessed using analysis of covariance. Serum enterolignans increased among the flaxseed arm (+516%). Women consuming flaxseed (vs. controls) had increased serum 2-hydroxyestrone [treatment effect ratio (TER) = 1.54; 95% CI: 1.18-2.00] and 2:16α-hydroxyestrone ratio (TER =1.54; 95% CI: 1.15-2.06); effects on other hormones were not statistically significant. Within the flaxseed arm, change in enterolignan level was positively correlated with changes in 2-hydroxyestrone and 2:16α-hydroxyestrone ratio, and negatively with prolactin. Findings suggest flaxseed affects certain circulating sex hormone levels with possible implications for future breast cancer prevention research.


Assuntos
Dieta , Linho , Hormônios Esteroides Gonadais/sangue , Pós-Menopausa/sangue , Neoplasias da Mama/prevenção & controle , Canadá , Feminino , Linho/efeitos adversos , Humanos , Hidroxiestronas/sangue , Lignanas/administração & dosagem , Lignanas/sangue , Pessoa de Meia-Idade , Prolactina/sangue
11.
Br J Nutr ; 122(5): 552-563, 2019 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-30173678

RESUMO

The association between lifestyle and survival after colorectal cancer has received limited attention. The female sex hormone, oestrogen, has been associated with lower colorectal cancer risk and mortality after colorectal cancer. Phyto-oestrogens are plant compounds with structure similar to oestrogen, and the main sources in Western populations are plant lignans. We investigated the association between the main lignan metabolite, enterolactone and survival after colorectal cancer among participants in the Danish Diet, Cancer and Health cohort. Prediagnosis plasma samples and lifestyle data, and clinical data from time of diagnosis from 416 women and 537 men diagnosed with colorectal cancer were used. Enterolactone was measured in plasma using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Participants were followed from date of diagnosis until death or end of follow-up. During this time, 210 women and 325 men died (170 women and 215 men died due to colorectal cancer). The Cox proportional hazards model was used to estimate hazard ratios (HR) and 95 % CI. Enterolactone concentrations were associated with lower colorectal cancer-specific mortality among women (HRper doubling: 0·88, 95 % CI 0·80, 0·97, P=0·0123). For men, on the contrary, enterolactone concentrations were associated with higher colorectal cancer-specific mortality (HRper doubling: 1·10, 95 % CI 1·01, 1·21, P=0·0379). The use of antibiotics affects enterolactone production, and the associations between higher enterolactone and lower colorectal cancer-specific mortality were more pronounced among women who did not use antibiotics (analysis on a subset). Our results suggest that enterolactone is associated with lower risk of mortality among women, but the opposite association was found among men.


Assuntos
4-Butirolactona/análogos & derivados , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Dieta , Lignanas/sangue , 4-Butirolactona/sangue , Idoso , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida
12.
Biomed Chromatogr ; 33(9): e4542, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30947404

RESUMO

A highly selective and efficient LC-MS/MS method was developed to determine the plasma concentration of magnolol, hesperidin, neohesperidin and geniposide following oral administration of Zhi-Zi-Hou-Po decoction in normal and depressed rats. Plasma samples were pretreated by protein precipitation with methanol. Chromatographic separation was performed on an XTerra® MS C18 column using a gradient elution with a mobile phase composed of acetonitrile-0.1% aqueous formic acid. The proposed method was validated to be specific, accurate and precise for the analytes determination in plasma samples. The calibration curves displayed good linearity over definite concentration ranges for the analytes. The intra- and inter-day precision of the proposed method at three different levels were all within <11.13% and the relative errors ranged from -8.46 to 8.93%. The recovery of the four compounds ranged from 82.72 to 89.08% and no apparent matrix effect was observed during sample analysis. After full validation, the established method was successfully applied for comparing the pharmacokinetics of four components between normal and depressed rats. The results showed that the AUC and Cmax of four analytes in depressed rats were significantly different from those in normal rats and might provide helpful information to guide the clinical use of Zhi-Zi-Hou-Po to treat depression.


Assuntos
Depressão , Medicamentos de Ervas Chinesas/farmacocinética , Iridoides/farmacocinética , Administração Oral , Animais , Compostos de Bifenilo/sangue , Compostos de Bifenilo/química , Compostos de Bifenilo/farmacocinética , Corticosterona/efeitos adversos , Depressão/induzido quimicamente , Depressão/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Hesperidina/sangue , Hesperidina/farmacocinética , Iridoides/administração & dosagem , Iridoides/sangue , Iridoides/química , Lignanas/sangue , Lignanas/química , Lignanas/farmacocinética , Limite de Detecção , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
13.
Int J Cancer ; 143(11): 2677-2686, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29971774

RESUMO

Phytoestrogens may influence prostate cancer development. This study aimed to examine the association between prediagnostic circulating concentrations of isoflavones (genistein, daidzein, equol) and lignans (enterolactone and enterodiol) and the risk of prostate cancer. Individual participant data were available from seven prospective studies (two studies from Japan with 241 cases and 503 controls and five studies from Europe with 2,828 cases and 5,593 controls). Because of the large difference in circulating isoflavone concentrations between Japan and Europe, analyses of the associations of isoflavone concentrations and prostate cancer risk were evaluated separately. Prostate cancer risk by study-specific fourths of circulating concentrations of each phytoestrogen was estimated using multivariable-adjusted conditional logistic regression. In men from Japan, those with high compared to low circulating equol concentrations had a lower risk of prostate cancer (multivariable-adjusted OR for upper quartile [Q4] vs. Q1 = 0.61, 95% confidence interval [CI] = 0.39-0.97), although there was no significant trend (OR per 75 percentile increase = 0.69, 95 CI = 0.46-1.05, ptrend = 0.085); Genistein and daidzein concentrations were not significantly associated with risk (ORs for Q4 vs. Q1 = 0.70, 0.45-1.10 and 0.71, 0.45-1.12, respectively). In men from Europe, circulating concentrations of genistein, daidzein and equol were not associated with risk. Circulating lignan concentrations were not associated with the risk of prostate cancer, overall or by disease aggressiveness or time to diagnosis. There was no strong evidence that prediagnostic circulating concentrations of isoflavones or lignans are associated with prostate cancer risk, although further research is warranted in populations where isoflavone intakes are high.


Assuntos
Isoflavonas/sangue , Lignanas/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/etiologia , Idoso , Estudos de Casos e Controles , Equol/sangue , Europa (Continente) , Genisteína/sangue , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Fitoestrógenos/sangue , Estudos Prospectivos , Fatores de Risco
14.
Int J Cancer ; 143(11): 2698-2708, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29974464

RESUMO

Higher lignan exposure has been associated with lower all-cause mortality (ACM) and breast cancer-specific mortality (BCSM) for postmenopausal breast cancer patients. However, the biological mechanisms underpinning these associations are still unclear. We investigated for the first time whether and to what extent the association between enterolactone (ENL), the major lignan metabolite, and postmenopausal breast cancer prognosis is mediated by inflammatory biomarkers. Circulating concentrations of ENL and inflammatory markers were measured in a population-based prospective cohort of 1,743 breast cancer patients recruited between 2002 and 2005 and followed-up until 2009. Hazard ratios (HR) and 95% CIs were estimated using multivariable Cox regression. Mediation analysis was performed to estimate the percentage association between ENL (log2) and ACM, BCSM and distant disease-free survival (DDFS), which is mediated by C-reactive protein (CRP) (log2), as the strongest potential mediator, and also interleukin (IL)-10. Median serum/plasma ENL and CRP concentrations for all patients, including 180 deceased patients, were 23.2 and 17.5 nmol/L, and 3.2 and 6.5 mg/l, respectively. ENL concentrations were significantly inversely associated with ACM, BCSM and DDFS (per doubling of ENL concentrations: HRs 0.93 [0.87, 0.99], 0.91 [0.84, 0.99] and 0.92 [0.87, 0.99]), after adjusting for prognostic factors and BMI. Estimated 18, 14 and 12% of the effects of ENL on ACM, BCSM and DDFS, respectively, were mediated through CRP. No mediational effect of IL-10 was found. We provide first evidence that the proinflammatory marker CRP may partially mediate the association of ENL with postmenopausal breast cancer survival, which supports hormone-independent mechanisms.


Assuntos
4-Butirolactona/análogos & derivados , Biomarcadores/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Inflamação/sangue , Lignanas/sangue , Pós-Menopausa/sangue , 4-Butirolactona/sangue , Idoso , Estudos de Casos e Controles , Intervalo Livre de Doença , Feminino , Humanos , Inflamação/patologia , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos
15.
Eur J Nutr ; 57(7): 2595-2606, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28884432

RESUMO

PURPOSE: Enterolactone (ENL) is formed in the human gut after consumption of lignans, has estrogenic properties, and has been associated with risk of prostate cancer. We examined the association between plasma ENL levels and prostate cancer in a nested case-control study within the population-based Malmö Diet and Cancer cohort. We also examined the association between plasma ENL and dietary and lifestyle factors. METHODS: The study population consisted of 1010 cases occurring during a mean follow-up of 14.6 years, and 1817 controls matched on age and study entry date. We used national registers (95%) and hospital records (5%) to ascertain cases. Diet was estimated by a modified diet history method. Plasma ENL concentrations were determined by a time-resolved fluoroimmunoassay. Odds ratios were calculated by unconditional logistic regression. RESULTS: There were no significant associations between plasma ENL and incidence of all prostate cancer (odds ratio 0.99 [95% confidence interval 0.77-1.280] for the highest ENL quintile versus lowest, p for trend 0.66). However, in certain subgroups of men, including men with abdominal obesity (p for interaction = 0.012), we observed associations between high ENL levels and lower odds of high-risk prostate cancer. Plasma ENL was positively associated with consumption of high-fibre bread, fruit, tea, and coffee; with age, and with height, while it was negatively associated with smoking and waist circumference; however, although significant, all associations were rather weak (r ≤ |0.14|). CONCLUSION: ENL concentration was not consistently associated with lower prostate cancer risk, although it was weakly associated with a healthy lifestyle.


Assuntos
4-Butirolactona/análogos & derivados , Lignanas/sangue , Neoplasias da Próstata/epidemiologia , 4-Butirolactona/sangue , Estudos de Casos e Controles , Humanos , Estilo de Vida , Lignanas/administração & dosagem , Lignanas/química , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/sangue , Fatores de Risco , Suécia
16.
BMC Vet Res ; 14(1): 14, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29334949

RESUMO

BACKGROUND: Flaxseed is the most common and rich dietary source of lignans and is an acceptable supply of energy for livestock. Flaxseed lignans are precursors of enterolignans, mainly enterolactone and enterodiol, produced by the rumen and intestinal microbiota of mammals and have many important biological properties as phytoestrogens. Potential food-drug interactions involving flaxseed may be relevant for veterinary therapy, and for the quality and safety of milk and dairy products. Our aim was to investigate a potential food-drug interaction involving flaxseed, to explore whether the inclusion of flaxseed in sheep diet affects concentration of the antimicrobial danofloxacin in milk. RESULTS: Increased concentrations of enterodiol and enterolactone were observed in sheep plasma and milk after 2 weeks of flaxseed supplementation (P < 0.05). However, enterolactone and enterodiol conjugates were not detected in milk. Milk danofloxacin pharmacokinetics showed that area under the curve (AUC)0-24, maximum concentration (Cmax) and AUC0-24 milk-to-plasma ratios were reduced by 25-30% in sheep fed flaxseed-enriched diets (P < 0.05). Our results demonstrate, therefore, that flaxseed-enriched diets reduce the amount of danofloxacin in sheep milk and enrich the milk content of lignan-derivatives. CONCLUSION: These findings highlight an effect of flaxseed-enriched diets on the concentration of antimicrobials in ruminant's milk, revealing the potential of these modified diets for the control of residues of antimicrobial drugs in milk.


Assuntos
Antibacterianos/farmacocinética , Dieta/veterinária , Linho , Fluoroquinolonas/farmacocinética , Leite/química , Ovinos/fisiologia , 4-Butirolactona/análogos & derivados , 4-Butirolactona/sangue , Ração Animal/análise , Animais , Antibacterianos/análise , Feminino , Fluoroquinolonas/análise , Interações Alimento-Droga , Lignanas/análise , Lignanas/sangue , Sementes
17.
J Sep Sci ; 41(16): 3328-3338, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29957847

RESUMO

Genkwa Flos, a famous traditional Chinese medicine has been reported to have significant hepatotoxicity. A high-throughput and reliable method was established to explore potential toxic components by high-performance liquid chromatography coupled with a Q Exactive high-performance benchtop quadrupole-Orbitrap mass spectrometer. A total of 68 compounds including 22 chemical components and 46 metabolites were tentatively identified based on the accurately measured mass value, retention time, and fragmentation pattern. Besides, the metabolic pathways of main components in Genkwa Flos were also illustrated. The results indicated that hydroxylation, demethylation, methylation, glucuronidation, sulfation, cysteine conjugation, and glutathione conjugation participated in the metabolic reactions of Genkwa Flos. Moreover, 12 Genkwa Flos chemical components and 26 metabolites were detected in cell lysate, which were considered as the bound components to HL-7702 cells. In view of cell affinity theory, these compounds were preliminarily deduced to be potential toxic ingredients for the hepatotoxicity induced by Genkwa Flos. The results demonstrated that the developed method was a very feasible and efficient approach for the components identification even in the complex matrix. In conclusion, this study will provide a deep insight into the toxic substances of Genkwa Flos and lay a chemical basis for in-depth toxic studies on Genkwa Flos hepatotoxicity.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Cumarínicos/sangue , Cumarínicos/metabolismo , Cumarínicos/toxicidade , Diterpenos/sangue , Diterpenos/metabolismo , Diterpenos/toxicidade , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Flavonoides/sangue , Flavonoides/metabolismo , Flavonoides/toxicidade , Glicosídeos/sangue , Glicosídeos/metabolismo , Glicosídeos/toxicidade , Humanos , Lignanas/sangue , Lignanas/metabolismo , Lignanas/toxicidade , Masculino , Espectrometria de Massas , Medicina Tradicional Chinesa , Estrutura Molecular , Ratos , Ratos Sprague-Dawley
18.
Biomed Chromatogr ; 32(8): e4256, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29644721

RESUMO

Yiqifumai Injection is a lyophilized powder preparation widely used to treat coronary heart disease. However, its in vivo bioactive components and pharmacokinetic behavior remain unknown. Therefore a sensitive and specific LC-MS/MS was developed and validated for the simultaneous quantification of eight saponins and four lignans in beagle dog plasma. The plasma samples were pretreated by protein precipitation with methanol-acetonitrile (1:1, v/v). Chromatographic separation of all the 12 analytes and estazolam (internal standard, IS) was successfully accomplished on an Ultimate® XB-C8 column (100 × 2.1 mm, 3 µm) with a gradient elution system. The total running time was 8 min with a flow rate of 0.40 mL/min. Acquisition of mass spectrometric data was performed via positive electrospray ionization in multiple reaction monitoring mode. The assay was fully validated in terms of selectivity, linear range, lower limit of quantitation, precision, accuracy, matrix effect, recovery and stability. This validated method was successfully applied to the pharmacokinetics of 12 bioactive components after intravenous administration of Yiqifumai Injection to beagle dogs at a dose of 0.541 g/kg.


Assuntos
Cromatografia Líquida/métodos , Medicamentos de Ervas Chinesas/farmacocinética , Lignanas/sangue , Saponinas/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Cães , Estabilidade de Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Lignanas/química , Lignanas/farmacocinética , Limite de Detecção , Modelos Lineares , Masculino , Reprodutibilidade dos Testes , Saponinas/química , Saponinas/farmacocinética , Espectrometria de Massas por Ionização por Electrospray/métodos
19.
Biomed Chromatogr ; 32(2)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28744886

RESUMO

A sensitive, specific and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of seven constituents of the Zaoren Anshen prescription (ZAP) in rat plasma after oral administration of the ZAP: spinosin, salvianic acid A, 6'''-feruloylspinosin, protocatechualdehyde, salvianolic acid B, schisandrin and deoxyschisandrin. The plasma samples and the internal standard (IS) sulfamethoxazole were extracted using acetonitrile. Chromatographic separation was performed with an Agilent HC-C18 column using a gradient elution profile and a mobile phase consisting of 0.01% formic acid in water (A) and acetonitrile (B). The analytes were quantified simultaneously in a single run using an ion trap mass spectrometer operated in the multiple reaction monitoring mode and electrospray ion-source polarity in the positive and negative modes. The calibration curves for spinosin, salvianic acid A, 6'''-feruloylspinosin, protocatechualdehyde, salvianolic acid B, schisandrin and deoxyschisandrin were linear over the concentration ranges of 2.90-1160, 2.50-1000, 1.80-720, 0.65-260, 2.50-1000, 8.00-1600 and 1.30-520 ng/mL, respectively. The intra- and inter-day precisions in terms of relative standard deviation were <18.9%, and the accuracies in terms of relative error were within ±14.2%. Consequently, the proposed method was successfully applied to the pharmacokinetic analysis of these seven major active compounds in rats administered ZAP. These results will facilitate research aiming to predict the effectiveness of the optimal dose of ZAP and might be beneficial for the therapeutic use of ZAP in the clinical setting.


Assuntos
Benzaldeídos/sangue , Benzofuranos/sangue , Catecóis/sangue , Ciclo-Octanos/sangue , Medicamentos de Ervas Chinesas/farmacocinética , Flavonoides/sangue , Lignanas/sangue , Compostos Policíclicos/sangue , Animais , Benzaldeídos/química , Benzaldeídos/farmacocinética , Benzofuranos/química , Benzofuranos/farmacocinética , Catecóis/química , Catecóis/farmacocinética , Cromatografia Líquida/métodos , Ciclo-Octanos/química , Ciclo-Octanos/farmacocinética , Estabilidade de Medicamentos , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Flavonoides/química , Flavonoides/farmacocinética , Lignanas/química , Lignanas/farmacocinética , Limite de Detecção , Modelos Lineares , Masculino , Compostos Policíclicos/química , Compostos Policíclicos/farmacocinética , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
20.
J Sep Sci ; 40(17): 3430-3439, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28675628

RESUMO

The aim of this study was to develop an analytical method to simultaneously analyze schizandrin, schizandrol B, and gomisin N lignans in human plasma using ultra high performance liquid chromatography with tandem mass spectrometry. The three lignans were separated using a mobile phase of water and acetonitrile containing 0.02% acetic acid equipped with a Kinetex C18 column (2.1 mm × 50 mm, 1.7 µm). This analysis was achieved by multiple reaction monitoring mode in an electrospray interface. The mass transitions were m/z 433.1→384.0 for schizandrin, 398.8→367.8 for schizandrol B, and 400.6→299.8 for gomisin N. Liquid-liquid extraction with methyl tert-butyl ether was used to obtain the three lignans. The chromatograms showed high resolution, sensitivity, and selectivity with no interference with plasma constituents. The calibration curves for the three lignans in human plasma were 0.05-50 ng/mL and displayed excellent linearity with correlation coefficients greater than 0.99. Precision for all three lignans was within 11.23%. The accuracy was 88.3-99.0% for schizandrin, 90.6-103.4% for schizandrol B, and 90.2-103.5% for gomisin N. The developed simultaneous analytical method satisfied the criteria of international guidance and could be successfully applied to the pharmacokinetic study of three lignans after oral administration of Schisandrae Fructus extract powder to humans.


Assuntos
Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/farmacocinética , Lignanas/sangue , Espectrometria de Massas em Tandem , Ciclo-Octanos/sangue , Dioxóis/sangue , Humanos , Compostos Policíclicos/sangue , Reprodutibilidade dos Testes
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