RESUMEN
Dietary isoflavones have been associated with a lower risk of gastric cancer (GC), but the evidence for this association is still limited. We investigated the association between isoflavone intake and GC risk using data from a case-control study including 230 incident, histologically confirmed GC cases and 547 controls with acute, non-neoplastic conditions. Dietary information was collected through a validated food frequency questionnaire (FFQ) and isoflavone intake was estimated using ad hoc databases. We estimated the odds ratios (OR) and the corresponding 95% confidence intervals (CI) of GC using logistic regression models, including terms for total energy intake and other major confounders. The OR for the highest versus the lowest tertile of intake was 0.65 (95%CI = 0.44-0.97, p for trend = 0.04) for daidzein, 0.75 (95%CI = 0.54-1.11, p for trend = 0.15) for genistein, and 0.66 (95%CI = 0.45-0.99, p for trend = 0.05) for total isoflavones. Stratified analyses by sex, age, education, and smoking showed no heterogeneity. These findings indicate a favorable effect of dietary isoflavones on GC.
Asunto(s)
Dieta , Isoflavonas , Neoplasias Gástricas , Humanos , Isoflavonas/administración & dosificación , Neoplasias Gástricas/prevención & control , Neoplasias Gástricas/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Estudios de Casos y Controles , Anciano , Dieta/estadística & datos numéricos , Oportunidad Relativa , Adulto , Factores de Riesgo , Genisteína/administración & dosificación , Modelos LogísticosRESUMEN
The phytoestrogens daidzein and genistein are ubiquitous in human food. This study aimed to elucidate their anxiety-liked effects, their effects on the reproductive organs, and the molecular mechanism behind any anxiety-liked effects in intact adult male Wistar rats. These phytoestrogens are of interest due to their posited health benefits, particularly for female, but with some effect on males as well. This study comprised two experiments: (1) Male Wistar rats received either a vehicle, daidzein, or genistein (0.25, 0.50, or 1.00â¯mg/kg) by subcutaneously injection for four weeks. They were then tested for anxiety-liked behaviors. Then, the brain monoamines in anxiolytic rats were determined; (2) The modulation of gamma aminobutyric acid receptors by phytoestrogens was further analyzed by administration of diazepam to phytoestrogen-treated rats before behavioral tests. In the first experiment, the biological parameters measured, including body weight, daily food intake and reproductive organ weights were unaffected by either genistein or daidzein. However, anxiolytic-like effect was observed in the low-dose daidzein (0.25â¯mg/kg) group. Higher doses of daidzein or genistein of all doses had no effect. Further, the low-dose daidzein did not alter brain monoamine levels. In the second experiment, the anxiolytic-like behavior of daidzein-treated rats receiving diazepam did not differ from that of the rats treated with just diazepam or just daidzein. In conclusion, 4-week exposure to daidzein or genistein had no negative effects on the reproductive organs, body weight, food intake, anxiogenic-like behavior, or monoaminergic and diazepam-modulated GABAergic neurotransmissions of intact male rats. However, beneficial anxiolytic-like effects were apparent after low-dose treatment with daidzein.
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Ansiolíticos , Ansiedad , Genisteína , Isoflavonas , Ratas Wistar , Animales , Masculino , Genisteína/farmacología , Genisteína/administración & dosificación , Ansiolíticos/farmacología , Ansiolíticos/administración & dosificación , Isoflavonas/farmacología , Isoflavonas/administración & dosificación , Ansiedad/tratamiento farmacológico , Ratas , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Relación Dosis-Respuesta a Droga , Fitoestrógenos/farmacología , Fitoestrógenos/administración & dosificación , Diazepam/farmacología , Ingestión de Alimentos/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacosRESUMEN
Purpose: Mitochondrial damage may lead to uncontrolled oxidative stress and massive apoptosis, and thus plays a pivotal role in the pathological processes of myocardial ischemia-reperfusion (I/R) injury. However, it is difficult for the drugs such as puerarin (PUE) to reach the mitochondrial lesion due to lack of targeting ability, which seriously affects the expected efficacy of drug therapy for myocardial I/R injury. Methods: We prepared triphenylphosphonium (TPP) cations and ischemic myocardium-targeting peptide (IMTP) co-modified puerarin-loaded liposomes (PUE@T/I-L), which effectively deliver the drug to mitochondria and improve the effectiveness of PUE in reducing myocardial I/R injury. Results: In vitro test results showed that PUE@T/I-L had sustained release and excellent hemocompatibility. Fluorescence test results showed that TPP cations and IMTP double-modified liposomes (T/I-L) enhanced the intracellular uptake, escaped lysosomal capture and promoted drug targeting into the mitochondria. Notably, PUE@T/I-L inhibited the opening of the mitochondrial permeability transition pore, reduced intracellular reactive oxygen species (ROS) levels and increased superoxide dismutase (SOD) levels, thereby decreasing the percentage of Hoechst-positive cells and improving the survival of hypoxia-reoxygenated (H/R)-injured H9c2 cells. In a mouse myocardial I/R injury model, PUE@T/I-L showed a significant myocardial protective effect against myocardial I/R injury by protecting mitochondrial integrity, reducing myocardial apoptosis and decreasing infarct size. Conclusion: This drug delivery system exhibited excellent mitochondrial targeting and reduction of myocardial apoptosis, which endowed it with good potential extension value in the precise treatment of myocardial I/R injury.
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Isoflavonas , Liposomas , Daño por Reperfusión Miocárdica , Compuestos Organofosforados , Animales , Liposomas/química , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Isoflavonas/química , Isoflavonas/farmacología , Isoflavonas/administración & dosificación , Isoflavonas/farmacocinética , Compuestos Organofosforados/química , Compuestos Organofosforados/farmacología , Compuestos Organofosforados/administración & dosificación , Compuestos Organofosforados/farmacocinética , Masculino , Ratones , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Cationes/química , Miocardio/patología , Miocardio/metabolismo , Estrés Oxidativo/efectos de los fármacos , Péptidos/química , Péptidos/farmacología , Péptidos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodosRESUMEN
ETHNO-PHARMACOLOGICAL RELEVANCE: Huangqi Gegen decoction (HGD), which comprises Astragali Radix (AR) and Puerariae Radix (PR), is widely used to treat thrombosis in China. However, the mechanism underlying its synergistic effect in thrombosis treatment remains unclear. AIM OF THE STUDY: Following PR administration, low plasma exposure was reported for its primary ingredients. In this regard, this study examined the effect of AR on PR's antithrombotic efficacy with respect to the impact of Astragalus Polysaccharide (APS) on the oral delivery of Puerarin (PUE). MATERIALS AND METHODS: To evaluate the synergistic effect of HGD, a thrombus mice model was established via intraperitoneal injection of carrageenan. After treatment, histopathological observations were made, and the proportion of thrombus length in the tail, as well as the plasma APTT, PT, INR, and FIB levels, were detected. Molecular docking was employed to assess the PR ingredients that could inhibit the HMGB1/NF-κB/NLRP3 pathway. The Pharmacokinetics of PR ingredients in rats were also compared between the PR and HGD groups. Moreover, the effect of APS on the solubility, intestinal absorption, and pharmacokinetics of PUE was evaluated. Furthermore, the impact of APS on the antithrombotic efficacy of PUE was assessed. RESULTS: In mice, AR enhanced the antithrombotic effect of PR. This improved PR effect was associated with isoflavones-induced downregulation of the HMGB1/NF-κB/NLRP3 pathway. The synergistic effect resulting from the compatibility of HGD components was primarily achieved by improving the plasma exposure of PR isoflavones. Specifically, APS enhanced PUE's water solubility through the formation of self-assembly Nanoparticles, increasing its intestinal absorption and oral bioavailability, which, in turn, suppressed the HMGB1/NF-κB/NLRP3 pathway, thus improving its antithrombotic effect. CONCLUSIONS: Our findings revealed that APS improved PUE's plasma exposure, enhancing its inhibitory effect on the HMGB1/NF-κB/NLRP3 pathway. This mechanism presents a key aspect of the synergistic effect of HGD compatibility in thrombosis treatment.
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Planta del Astrágalo , Sinergismo Farmacológico , Medicamentos Herbarios Chinos , Isoflavonas , Polisacáridos , Trombosis , Animales , Isoflavonas/farmacología , Isoflavonas/administración & dosificación , Isoflavonas/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Polisacáridos/farmacología , Polisacáridos/administración & dosificación , Masculino , Administración Oral , Trombosis/tratamiento farmacológico , Ratones , Planta del Astrágalo/química , Fibrinolíticos/farmacología , Fibrinolíticos/administración & dosificación , Pueraria/química , Modelos Animales de Enfermedad , Simulación del Acoplamiento Molecular , Astragalus propinquus/química , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismoRESUMEN
BACKGROUND: Many studies have investigated the intake of dietary isoflavones in relation to obesity risk, whereas the association using objective biomarkers of isoflavones, particularly equol (a gut-derived metabolite of daidzein with greater bioavailability than other isoflavones) has been less studied. In addition, the associations between equol and gut microbiota profile at the population level remain to be fully characterized. OBJECTIVES: We aimed to identify equol-predicting microbial species and to investigate the associations of equol-predicting microbial species and urinary excretion of isoflavones including glycitein, genistein, daidzein, and equol with diverse obesity markers in free living-individuals. METHODS: In this 1-y longitudinal study of 754 community-dwelling adults, urinary isoflavones, fecal microbiota, height, weight, and circumferences of waist and hip were measured at baseline and again after 1 y. Liver fat [indicated by the controlled attenuation parameter (CAP)] and other body composition were also measured after 1 y. Linear models and linear mixed-effects models were used to analyze the associations for single measure and repeated measures, respectively. RESULTS: Among 305 participants (median age: 50 y, IQR, 37-59 y) including 138 males and 167 females, higher urinary excretion of equol was associated with lower CAP (ß = -0.013, P < 0.001) and body fat mass (ß= -0.014, P = 0.046). No association was found between any other urinary isoflavones and obesity markers (all P > 0.05). We identified 21 bacterial genera whose relative abundance were positively associated with urinary equol concentrations (all Pfalsediscovery rate < 0.05), and constructed an equol-predicting microbial score to reflect the overall equol-producing potential of host gut microbiota. This score was inversely associated with CAP (ß = -0.040, P = 0.011). CONCLUSIONS: High urinary equol concentrations and equol-predicting microbial species could be favorably associated with liver fat and other obesity markers.
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Equol , Microbioma Gastrointestinal , Isoflavonas , Humanos , Equol/orina , Femenino , Masculino , Persona de Mediana Edad , Adulto , Estudios Longitudinales , Isoflavonas/orina , Isoflavonas/administración & dosificación , Tejido Adiposo/metabolismo , China , Obesidad/orina , Obesidad/microbiología , Biomarcadores/orina , Pueblo Asiatico , Bacterias/clasificación , Bacterias/metabolismo , Heces/microbiología , Heces/química , Pueblos del Este de AsiaRESUMEN
Osteoporosis is characterized by bone loss and deterioration in bone microstructure, leading to bone fragility. It is strongly correlated with menopause in women. Previously, we reported that diets supplemented with a kudzu (Pueraria lobata) vine extract suppressed bone resorption in ovariectomized (OVX) mice, a postmenopausal model. The main isoflavone in kudzu is puerarin (daidzein-8-C-glycoside). Puerarin (daidzein-8-C-glycoside), which is main isoflavone of kudzu, probably contributes to the beneficial effect. However, the underlying mechanism is unclear. Therefore, the nutrikinetics of puerarin and the comparison with the suppressive effects of kudzu isoflavones on osteoclast differentiation was examined in this study. We demonstrated that orally administered puerarin was absorbed from the gut and entered the circulation in an intact form. In addition, puerarin accumulated in RAW264.7 pre-osteoclast cells in a time-dependent manner. Tartrate-resistant acid phosphatase activity was decreased by puerarin treatment in a concentration-dependent manner in RAW264.7 cells stimulated with the receptor activator of nuclear factor kappa-B ligand. Ovariectomy-induced elevated bone resorption was suppressed, and the fragile bone strength was improved by puerarin ingestion in the diet. These findings suggested that orally administered puerarin was localized in bone tissue and suppressed bone resorption and osteoclastogenesis in ovariectomized mice.
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Diferenciación Celular , Fémur , Isoflavonas , Osteoclastos , Ovariectomía , Pueraria , Animales , Isoflavonas/farmacología , Isoflavonas/administración & dosificación , Osteoclastos/efectos de los fármacos , Femenino , Ratones , Fémur/efectos de los fármacos , Fémur/metabolismo , Pueraria/química , Diferenciación Celular/efectos de los fármacos , Células RAW 264.7 , Resorción Ósea/prevención & control , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Osteoporosis/prevención & control , Osteoporosis/tratamiento farmacológico , Fosfatasa Ácida Tartratorresistente/metabolismoRESUMEN
SUMMARY: Spinal cord injury (SCI) usually arises from compression due to traffic accidents and falls, resulting in varying degrees of movement, sensory loss, and possible paralysis. Glabridin (Gla) is a natural compound derived from licorice. It significantly affects drug development and medicine because of its anti-inflammatory, anti-oxidative, anti-tumoral, antibacterial, bone protective, cardiovascular protective, neuroprotective, liver protective, anti-obesity, and anti-diabetic properties. Various methods were employed to administer Gla to SCI mice in order to investigate its impact on the recovery of motor function. The mice were allocated into four cohorts using a randomization procedure. In the sham cohort, solely the lamina of vertebral arch was surgically exposed without causing any harm to the spinal cord tissue. Conversely, the injury cohort was subjected to spinal cord tissue damage and received no treatment thereafter. The mice in the remaining two cohorts received a dosage of 40 mg/kg Gla every two days via either intraperitoneal or intrathecal injection for a duration of 42 d following spinal cord injury. We conducted behavioral tests utilizing the Basso Mouse Scale score and gait analysis techniques. Magnetic resonance imaging and hematoxylin and eosin were employed to evaluate scar tissue formation. Systemic inflammation in mice was evaluated by employing an enzyme-linked immunosorbent assay. Gla promoted motor function recovery in mice following SCI and improved the pathological environment in the damaged area. These alterations were more evident in mice subjected to the intrathecal injection method. Intraperitoneal injections appear to be more beneficial for controlling systemic inflammatory responses. Although more intensive studies are required, Gla exhibits promising clinical potential as a cost-effective dietary phytochemical.
La lesión de la médula espinal (LME) generalmente surge de la compresión producto de caídas y accidentes de tránsito, lo que resulta en alteraciones del movimiento, pérdida sensorial y posible parálisis. La Glabridina (Gla) es un compuesto natural derivado del regaliz, constituyéndose en un aporte significativo para el desarrollo de fármacos y la medicina debido a sus propiedades antiinflamatorias, antioxidantes, antitumorales, antibacterianas, osteoprotectoras, cardioprotectoras, neuroprotectoras, hepatoprotectoras, antidiabéticas y contra la obesidad. En el presente trabajo se emplearon varios métodos para administrar Gla a ratones con lesión medular con el fin de investigar su impacto en la recuperación de la función motora. Los ratones fueron distribuidos en cuatro grupos mediante un procedimiento de aleatorización. En el grupo simulado, únicamente se expuso quirúrgicamente la lámina del arco vertebral sin causar ningún daño al tejido de la médula espinal. Por el contrario, el grupo lesionado fue sometido a daño del tejido de la médula espinal, sin recibir tratamiento posterior. Los ratones de los dos grupos restantes recibieron una dosis de 40 mg/kg de Gla cada dos días mediante inyección intraperitoneal o intratecal durante 42 días después de la lesión de la médula espinal. Fueron realizadas pruebas de comportamiento utilizando la puntuación de la escala Basso Mouse y técnicas de análisis de la marcha. Se emplearon imágenes por resonancia magnética y se aplicaron tinciones histológicas (Hematoxilina & Eosina) en muestras para evaluar la formación de tejido cicatricial. La inflamación sistémica en ratones se evaluó mediante el empleo de un ensayo inmunoabsorbente ligado a enzimas. Gla promovió la recuperación de la función motora en ratones después de una lesión medular y mejoró el entorno patológico en el área dañada. Estas alteraciones fueron más evidentes en ratones sometidos al método de inyección intratecal. Las inyecciones intraperitoneales parecen ser más beneficiosas para controlar las respuestas inflamatorias sistémicas. Aunque se requieren estudios más intensivos, Gla exhibe un potencial clínico prometedor como fitoquímico dietético rentable.
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Animales , Femenino , Ratones , Fenoles/administración & dosificación , Traumatismos de la Médula Espinal/tratamiento farmacológico , Isoflavonas/administración & dosificación , Ensayo de Inmunoadsorción Enzimática , Supervivencia Celular , Técnica del Anticuerpo Fluorescente , Fármacos Neuroprotectores , Recuperación de la Función , Ratones Endogámicos C57BL , Actividad Motora/efectos de los fármacosRESUMEN
BACKGROUND: Fermented soy products have shown to possess inhibitory effects on prostate cancer (PCa). We evaluated the effect of a fermented soy beverage (Q-Can®), containing medium-chain triglycerides, ketones and soy isoflavones, among men with localized PCa prior to radical prostatectomy. METHODS: We conducted a placebo-controlled, double-blind randomized trial of Q-Can®. Stratified randomization (Cancer of the Prostate Risk Assessment (CAPRA) score at diagnosis) was used to assign patients to receive Q-Can® or placebo for 2-5 weeks before RP. Primary endpoint was change in serum PSA from baseline to end-of-study. We assessed changes in other clinical and pathologic endpoints. The primary ITT analysis compared PSA at end-of-study between randomization arms using repeated measures linear mixed model incorporating baseline CAPRA risk strata. RESULTS: We randomized 19 patients, 16 were eligible for analysis of the primary outcome. Mean age at enrollment was 61, 9(56.2%) were classified as low and intermediate risk, and 7(43.8%) high CAPRA risk. Among patients who received Q-Can®, mean PSA at baseline and end-of-study was 8.98(standard deviation, SD 4.07) and 8.02ng/mL(SD 3.99) compared with 8.66(SD 2.71) to 9.53ng/mL(SD 3.03), respectively, (Difference baseline - end-of-study, p = 0.36). There were no significant differences in Gleason score, clinical stage, surgical margin status, or CAPRA score between treatment arms (p > 0.05), and no significant differences between treatment arms in end-of-study or change in lipids, testosterone and FACT-P scores (p > 0.05). CONCLUSIONS: Short exposure to Q-Can® among patients with localized PCa was not associated with changes in PSA levels, PCa characteristics including grade and stage or serum testosterone. Due to early termination from inability to recruit, study power, was not achieved.
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Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Prostatectomía/métodos , Persona de Mediana Edad , Método Doble Ciego , Anciano , Antígeno Prostático Específico/sangre , Alimentos de Soja , Fermentación , Bebidas , Isoflavonas/uso terapéutico , Isoflavonas/administración & dosificación , Glycine max , Cuidados Preoperatorios/métodosRESUMEN
Background and Objectives: Hormonal changes physiologically occurring in menopausal women may increase the risk of developing metabolic and vasomotor disturbances, which contribute to increase the risk of developing other concomitant pathologies, such as metabolic syndrome (MetS). Materials and Methods: Retrospective data from 200 menopausal women with MetS and vasomotor symptoms taking one sachet per day of the dietary supplement INOFOLIC® NRT (Farmares srl, Rome, Italy) were collected. Each sachet consisted of myo-Inositol (2000 mg), cocoa polyphenols (30 mg), and soy isoflavones (80 mg, of which 50 mg is genistin). Patients recorded their symptoms through a medical questionnaire at the beginning of the administration (T0) and after 6 months (T1). Results: We observed an improvement in both the frequency and the severity of hot flushes: increased percentage of 2-3 hot flushes (28 at T0 vs. 65% at T1, p value < 0.001) and decreased percentage of 4-9 hot flushes (54% at T0 vs. 18% at T1, p value < 0.001). Moreover, symptoms of depression improved after supplementation (87% at T0 vs. 56% at T1 of patients reported moderate depression symptoms, p value < 0.001). Regarding metabolic profile, women improved body mass index and waist circumference with a reduction in the percentage of overweight and obesity women (88% at T0 vs. 51% at T1, p value = 0.01; 14% at T0 vs. 9% at T1, p value = 0.04). In addition, the number of women suffering from non-insulin dependent diabetes reduced (26% at T0 vs. 16% at T1, p value = 0.04). Conclusions: These data corroborate previously observed beneficial effects of the oral administration of myo-Inositol, cocoa polyphenols, and soy isoflavones against menopausal symptoms in the study population. Considering the promising results of the present study, further prospective controlled clinical trials are needed to deeply understand and support the efficacy of these natural compounds for the management of menopausal symptoms.
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Suplementos Dietéticos , Glycine max , Sofocos , Inositol , Isoflavonas , Menopausia , Síndrome Metabólico , Polifenoles , Humanos , Femenino , Síndrome Metabólico/tratamiento farmacológico , Estudios Retrospectivos , Isoflavonas/uso terapéutico , Isoflavonas/farmacología , Isoflavonas/administración & dosificación , Persona de Mediana Edad , Polifenoles/administración & dosificación , Polifenoles/uso terapéutico , Polifenoles/análisis , Inositol/uso terapéutico , Inositol/administración & dosificación , Inositol/análisis , Sofocos/tratamiento farmacológico , Menopausia/efectos de los fármacos , Menopausia/fisiología , Cacao , Metaboloma/efectos de los fármacosRESUMEN
Osteoporosis is a disease that causes low bone mass and deterioration of bone microarchitecture. Puerarin is a natural isoflavone compound that has been shown to possess anti-inflammatory, antioxidant and ameliorative effects on osteoporosis with less adverse reactions. However, its fast metabolism and low oral bioavailability limit its application. This study aimed to prepare d-α-tocopherol polyethylene glycol 1000 succinate (TPGS)- modified Puerarin Long Circulating Liposomes (TPGS-Puerarin-liposomes), in order to improve the oral bioavailability of puerarin, before evaluation of its pharmacological activity in vitro and in vivo. We employed film dispersion method to develop TPGS-Puerarin-liposomes before appropriate characterizations. Afterwards, we utilized in vivo imaging, pharmacokinetic analysis and in vitro drug release testing to further evaluate the in vivo and in vitro delivery efficiency. In addition, we established a castrated osteoporosis rat model to observe the changes in femur tissue structure and bone micromorphology via hematoxylin-eosin (HE) staining and Micro Computed Tomography (Micro CT). Besides, levels of oxidative stress and inflammatory indicators, as well as expression of wnt/ß-catenin pathway-related proteins were detected. In terms of physiochemical properties, the respective mean particle size (PS) and zeta potential (ZP) of TPGS-Puerarin-liposomes were 76.63±0.59â¯nm and -25.54±0.11â¯mV. The liposomal formulation exhibited encapsulation efficiency (EE) of 95.08±0.25% and drug loading (DL) of 7.84±0.07%, along with excellent storage stability. Compared with free drugs, the TPGS-Puerarin-liposomes demonstrated a sustained release effect and could increase blood concentration of puerarin in rats, thereby significantly improving its bioavailability. Also, in vivo studies have confirmed potential of the liposomes to promote bone tissue targeting and accumulation of puerarin, coupled with significant improvement of the osteoporotic status. Besides, the liposomes could also reduce levels of oxidative stress and inflammatory factors in serum and bone tissue. Additionally, we discovered that TPGS-Puerarin-liposomes increased Wnt, ß-catenin and T-cell factor (TCF) expressions at protein level in the wnt/ß-catenin signaling pathway. This study has demonstrated the potential of TPGS-Puerarin-liposomes for treatment of osteoporosis.
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Isoflavonas , Liposomas , Osteoporosis , Ratas Sprague-Dawley , Vitamina E , Animales , Isoflavonas/administración & dosificación , Isoflavonas/farmacocinética , Isoflavonas/farmacología , Isoflavonas/química , Osteoporosis/tratamiento farmacológico , Ratas , Vitamina E/química , Vitamina E/administración & dosificación , Masculino , Disponibilidad Biológica , Liberación de Fármacos , Estrés Oxidativo/efectos de los fármacos , Polietilenglicoles/química , Fémur/efectos de los fármacos , Fémur/metabolismo , Antioxidantes/farmacocinética , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Administración Oral , Microtomografía por Rayos XRESUMEN
BACKGROUND: Several studies have shown that dietary isoflavones are negatively correlated with total cholesterol and low-density lipoprotein cholesterol. However, few studies have investigated the link between dietary isoflavones and remnant cholesterol (RC). OBJECTIVES: We used the National Health and Nutrition Examination Survey (NHANES) database to explore the association between dietary isoflavone intake and RC. METHODS: A cross-sectional study was conducted with 4731 participants aged ≥ 20 years from the 2007-2008, 2009-2010, and 2017-2018 NHANES databases. We adopted univariate and multiple linear regression analysis and restricted cubic spline (RCS) to assess the relationship between dietary isoflavone intake and RC. Moreover, we conducted stratified and interaction analyses to ensure the stability of the results and identify specific populations. RESULTS: The weighted multifactor linear regression model showed a negative correlation between dietary isoflavone intake and remnant cholesterol (Model 2, ß = -0.049, 95% CI: (-0.096, -0.002), P = 0.040). The RCS analysis indicated that there was an L-shaped negative correlation between dietary isoflavone intake and RC (P-value for non-linearity was 0.0464). Stratified analyses showed the inverse relationship between dietary isoflavone intake and RC persisted in most subgroups and there was no interaction except for the recreational activity group. CONCLUSIONS: Our study found a non-linear and negative association between dietary isoflavone intake and RC in US adults, so we hypothesized that consuming an isoflavone-rich diet may help reduce blood RC and further reduce the risk of cardiovascular disease.
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Colesterol , Isoflavonas , Encuestas Nutricionales , Humanos , Isoflavonas/administración & dosificación , Estudios Transversales , Masculino , Femenino , Encuestas Nutricionales/métodos , Colesterol/sangre , Adulto , Persona de Mediana Edad , Estados Unidos/epidemiología , Dieta/estadística & datos numéricos , Dieta/métodos , AncianoRESUMEN
BACKGROUND: Previous experimental studies have suggested that the consumption of soy isoflavones may have a potential impact on lowering blood pressure. Nevertheless, epidemiological studies have presented conflicting outcomes concerning the correlation between soy isoflavone consumption and blood pressure levels. Consequently, a comprehensive meta-analysis of all eligible randomized controlled trials (RCTs) was conducted to explore the influence of soy isoflavones on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults. METHODS: A thorough search of PubMed, Embase, and the Cochrane Library for relevant literature up to April 30, 2023 was conducted. RCTs involving adults that compared soy isoflavone supplementation with a placebo (the same matrix devoid of soy isoflavone) were included. The combined effect size was presented as the weighted mean difference (WMD) along with 95% confidence interval (CI), employing a fixed-effects model. RESULTS: Our meta-analysis included a total of 24 studies involving 1945 participants. The results revealed a significant reduction in both SBP and DBP with soy isoflavone supplementation. Subgroup analyses suggested more pronounced reductions in SBP and DBP for interventions lasting ≥6 months, in individuals receiving mixed-type soy isoflavone, and among patients with metabolic syndrome or prehypertension. However, we did not detect significant nonlinear associations between supplementation dosage and intervention duration concerning both SBP and DBP. The overall quality of evidence was deemed moderate. CONCLUSIONS: The current meta-analysis revealed that supplementation with soy isoflavones alone effectively reduces blood pressure. Additional high-quality studies are required to investigate the efficacy of blood pressure reduction through supplementation with an optimal quantity and proportion of soy isoflavone.
Asunto(s)
Hipertensión , Isoflavonas , Humanos , Presión Sanguínea , Suplementos Dietéticos , Hipertensión/tratamiento farmacológico , Hipertensión/prevención & control , Isoflavonas/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The aim of this study was to investigate the effects of puerarin (Pue), a phytoestrogen, on the production performance, egg quality, endocrine hormones, antioxidant capacity, and intestinal morphology in aged laying hens. A total of 180 Hy-Line Brown hens aged 480 d were randomly divided into 4 groups (n = 45 per group) and fed 0, 200, 400, and 800 mg/kg of Pue (Con, L-Pue, M-Pue, and H-Pue, respectively) during a 42-d experiment. Compared with the Con treatment, supplementation with H-Pue improved laying performance and egg quality by significantly increasing egg production, average egg weight, albumen height, yolk weight, and Haugh unit (P < 0.05) while decreasing the feed conversion ratio (P < 0.05). A diet supplemented with H-Pue significantly decreasing serum total triglycerides, total cholesterol, and low-density lipoprotein cholesterol, alanine aminotransferase (P < 0.05), and significantly increasing serum levels of follicle-stimulating hormone, luteinizing hormone and progesterone (P < 0.05). Antioxidant activity was improved by significantly increasing the activity of total antioxidant capacity, glutathione peroxidase and catalase but decreasing malondialdehyde levels in serum, jejunum, and ileum (P < 0.05), and superoxide dismutase activity exhibited a significantly increase in the jejunum and ileum (P < 0.05). Villus height and the ratio of villus height to crypt depth (P < 0.05) were significantly increased in the jejunum and ileum. In the jejunal and ileal mucosa, the three treatment groups increased the mRNA expression levels of Claudin-1 and Claudin-2 compared with Con (P < 0.05), and no significant effect was observed on the expression of Occludin and ZO-1. The results showed that dietary supplementation with Pue could improve the laying performance, egg quality, antioxidant capacity, hormonal profile, and intestinal morphology of aged laying hens.
Asunto(s)
Alimentación Animal , Antioxidantes , Pollos , Dieta , Suplementos Dietéticos , Isoflavonas , Distribución Aleatoria , Animales , Pollos/fisiología , Isoflavonas/farmacología , Isoflavonas/administración & dosificación , Femenino , Alimentación Animal/análisis , Suplementos Dietéticos/análisis , Antioxidantes/metabolismo , Dieta/veterinaria , Intestinos/efectos de los fármacos , Intestinos/anatomía & histología , Intestinos/fisiología , Óvulo/efectos de los fármacos , Óvulo/fisiología , Relación Dosis-Respuesta a Droga , Reproducción/efectos de los fármacosRESUMEN
Estrogen plays a crucial role in ovarian tumorigenesis. Phytoestrogens (PEs) are a type of daily dietary nutrient for humans and possess a mild estrogenic characteristic. This study aimed to assess the correlation of the consumption of dietary PEs with ovarian cancer risk using data in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial. Participants were enrolled in PLCO from 1993 to 2001. Hazard ratios (HR) and 95% confidence intervals (CI) were utilized to determine the association between the intake of PEs and ovarian cancer occurrence, which were calculated by the Cox proportional hazards regression analysis. In total, 24 875 participants were identified upon completion of the initial dietary questionnaire (DQX). Furthermore, the analysis also included a total of 45 472 women who filled out the diet history questionnaire (DHQ). Overall, after adjustment for confounders, the dietary intake of total PEs was significantly associated with the risk of ovarian cancer in the DHQ group (HRQ4vsQ1â =â 0.69, 95% CI: 0.50-0.95; P for trendâ =â 0.066). Especially, individuals who consumed the highest quartile of isoflavones were found to have a decreased risk of ovarian cancer in the DHQ group (HRQ4vsQ1â =â 0.68, 95% CI: 0.50-0.94; P for trendâ =â 0.032). However, no such significant associations were observed for the DQX group. In summary, this study suggests that increased dietary intake of total PEs especially isoflavones was linked with a lower risk for developing ovarian cancer. More research is necessary to validate the findings and explore the potential mechanisms.
Asunto(s)
Dieta , Neoplasias Ováricas , Fitoestrógenos , Humanos , Femenino , Fitoestrógenos/administración & dosificación , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/prevención & control , Neoplasias Ováricas/etiología , Estudios Prospectivos , Persona de Mediana Edad , Factores de Riesgo , Masculino , Anciano , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/prevención & control , Encuestas y Cuestionarios , Isoflavonas/administración & dosificación , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/prevención & control , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/etiologíaRESUMEN
Chimeric antigen receptor natural killer (CAR-NK) cell therapy represents a potent approach to suppressing tumor growth because it has simultaneously inherited the specificity of CAR and the intrinsic generality of NK cells in recognizing cancer cells. However, its therapeutic potency against solid tumors is still restricted by insufficient tumor infiltration, immunosuppressive tumor microenvironments, and many other biological barriers. Motivated by the high potency of puerarin, a traditional Chinese medicine extract, in dilating tumor blood vessels, an injectable puerarin depot based on a hydrogen peroxide-responsive hydrogel comprising poly(ethylene glycol) dimethacrylate and ferrous chloride is concisely developed. Upon intratumoral fixation, the as-prepared puerarin depot (abbreviated as puerarin@PEGel) can activate nitrogen oxide production inside endothelial cells and thus dilate tumor blood vessels to relieve tumor hypoxia and reverse tumor immunosuppression. Such treatment can thus promote tumor infiltration, survival, and effector functions of customized epidermal growth factor receptor (HER1)-targeted HER1-CAR-NK cells after intravenous administration. Consequently, such puerarin@PEGel-assisted HER1-CAR-NK cell treatment exhibits superior tumor suppression efficacy toward both HER1-overexpressing MDA-MB-468 and NCI-H23 human tumor xenografts in mice without inducing obvious side effects. This study highlights a potent strategy to activate CAR-NK cells for augmented treatment of targeted solid tumors through reprogramming tumor immunosuppression.
Asunto(s)
Inmunoterapia , Isoflavonas , Células Asesinas Naturales , Receptores Quiméricos de Antígenos , Humanos , Animales , Células Asesinas Naturales/inmunología , Isoflavonas/farmacología , Isoflavonas/química , Isoflavonas/administración & dosificación , Isoflavonas/uso terapéutico , Inmunoterapia/métodos , Línea Celular Tumoral , Neoplasias/terapia , Ratones , Terapia de Inmunosupresión , Microambiente Tumoral/efectos de los fármacos , InyeccionesRESUMEN
Salmonella enterica is a zoonotic bacterium that not only causes serious economic losses to the livestock and poultry industries but also seriously endangers human health. Long-term indiscriminate use of antibiotics has led to drug resistance in Salmonella, and thus the identification of alternatives to antibiotics is crucial. In this study, the effects of puerarin on the S. enterica-infected chickens were investigated. A total of 360 chicks were randomly assigned as the control group (CON), the S. enterica group (S), and puerarin-treatment group (P). Chicks in the P group were fed the basal diet supplemented with 50 (P50), 100 (P100), 200 (P200), and 400 (P400) mg/kg puerarin, respectively. It was found that puerarin treatment markedly altered the serum activities of aspartate aminotransferase (AST), alanine transaminase (ALT), and superoxide dismutase (SOD), together with the malondialdehyde (MDA) and total antioxidant capacity (T-AOC) contents in the serum. The mRNA expression of IL-6, IL-1ß, TNF-α, Bcl-2, and caspase-8 in the livers of S. enterica-infected chicks was increased after infection but significantly reduced after treatment with puerarin. Histologic analysis showed that puerarin effectively mitigated morphological damage in the liver caused by S. enterica. Proteomic analysis revealed that S. enterica infection led to metabolic disorders in the liver, resulting in oxidative stress, increased inflammation, and significantly elevated levels of hepatocellular carcinoma biomarkers. The findings of the filtered sequencing were verified by using quantitative PCR (qPCR). Treatment with 100 mg/mL puerarin thus effectively alleviated disordered liver metabolism, reduced inflammation and oxidative damage and significantly reduced the levels of hepatocellular carcinoma biomarkers in the liver. The results suggest that puerarin has the potential to replace antibiotics to control Salmonella infection in poultry and thus improve food safety.
Asunto(s)
Pollos , Isoflavonas , Hígado , Salmonelosis Animal , Animales , Antibacterianos/metabolismo , Biomarcadores/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/microbiología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/veterinaria , Pollos/metabolismo , Pollos/microbiología , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/microbiología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/microbiología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/veterinaria , Estrés Oxidativo , Proteómica , Salmonella/efectos de los fármacos , Inocuidad de los Alimentos , Salmonelosis Animal/complicaciones , Salmonelosis Animal/tratamiento farmacológico , Salmonelosis Animal/microbiología , Isoflavonas/administración & dosificaciónRESUMEN
Lung cancer is the most common cause of cancer-related mortality, chemo-resistance, and toxicity limit treatment. The focus is on innovative combined phytotherapy to improve treatment outcomes. Our aim was to investigate the potential effects of daidzein nanosuspension (DZ-NS) and its combination with cisplatin (CIS) on A549 non-small lung cancer cells. Cytotoxicity was investigated using MTT and Chou-Talalay methods. Oxidative, apoptotic, and inflammatory markers were analyzed by ELISA and qRT-PCR. The IC50 value for DZ-NS was 25.23 µM for 24 h and was lower than pure DZ (IC50 = 835 µM for pure DZ). DZ-NS (at IC50x2 and IC50 values) showed synergistic cytotoxicity with CIS. The cells treated with DZ-NS had low TOS and OSI levels. However, DZ-NS failed to regulate Cas3 and TGF-ß1 activation in A549 cells. MMP-9 gene expression was significantly suppressed in DZ-NS-treated cells, especially in combination therapy. DZ represents a potential combination option for the treatment of lung cancer, and its poor toxicokinetic properties limit its clinical use. To overcome these limitations, the effects of the nanosuspension formulation were tested. DZ-NS showed a cytotoxic effect on A549 cells and optimized the therapeutic effect of CIS. This in vitro synergistic effect was mediated by suppression of MMP-9 and not by oxidative stress or Cas3-activated apoptosis. This study provides the basis for an in vivo and clinical trial of DZ-NS with concurrent chemotherapy.
Asunto(s)
Apoptosis , Carcinoma de Pulmón de Células no Pequeñas , Cisplatino , Sinergismo Farmacológico , Isoflavonas , Neoplasias Pulmonares , Humanos , Cisplatino/farmacología , Cisplatino/administración & dosificación , Células A549 , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Isoflavonas/farmacología , Isoflavonas/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Apoptosis/efectos de los fármacos , Nanopartículas , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Suspensiones , Estrés Oxidativo/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genéticaRESUMEN
Diabetic nephropathy (DN) is an important complication of diabetes and is the main cause of end-stage renal disease. The pathogenesis of DN is complex, including glucose and lipid metabolism disorder, inflammation, and so on. Novel hybrid micelles loaded Puerarin (Pue) based on Angelica sinensis polysaccharides (ASP) and Astragalus polysaccharide (APS) were fabricated with pH-responsive ASP-hydrazone-ibuprofen (BF) materials (ASP-HZ-BF, SHB) and sialic acid (SA) modified APS-hydrazone-ibuprofen materials (SA/APS-HZ-BF, SPHB) by thin-film dispersion method. The SA in hybrid micelles can specifically bind to the E-selectin receptor which is highly expressed in inflammatory vascular endothelial cells. The loaded Pue could be accurately delivered to the inflammatory site of the kidney in response to the low pH microenvironment. Overall, this study provides a promising strategy for developing hybrid micelles based on natural polysaccharides for the treatment of diabetic nephropathy by inhibiting renal inflammatory reactions, and antioxidant stress.
Asunto(s)
Diabetes Mellitus Experimental , Neuropatías Diabéticas , Portadores de Fármacos , Selectina E , Isoflavonas , Concentración de Iones de Hidrógeno , Selectina E/metabolismo , Micelas , Neuropatías Diabéticas/tratamiento farmacológico , Isoflavonas/administración & dosificación , Angelica sinensis/química , Planta del Astrágalo/química , Polisacáridos/química , Riñón , Inflamación/tratamiento farmacológico , Ibuprofeno/química , Ácidos Siálicos/química , Unión Proteica , Diabetes Mellitus Experimental/inducido químicamente , Estreptozocina , Animales , Ratones , Masculino , Ratones Endogámicos C57BLRESUMEN
Myocardial fibrosis is a concomitant bioprocess associated with many cardiovascular diseases (CVDs). Daidzein is an isoflavone that has been used for the treatment of CVDs. This study aimed to reveal its role in myocardial fibrosis. Our results indicate that daidzein had a nontoxic effect on cardiac fibroblasts and that TGF-ß1 and TGFßRI levels were gradually decreased by daidzein in a dose-dependent manner. In the current study, we show that daidzein significantly inhibited TGF-ß1-induced mRNA and protein expression of α-SMA, collagen I, and collagen III. Accordingly, immunofluorescence staining of α-SMA was performed. Daidzein also inhibited TGF-ß1-induced cardiac fibroblast proliferation and migration. Mechanistically, daidzein inhibited the TGF-ß/SMAD signaling pathway induced by TGF-ß1 in cardiac fibroblasts. Additionally, daidzein ameliorated MI-induced cardiac dysfunction and cardiac fibrosis in vivo. Based on these findings, we conclude that daidzein reduces TGF-ß1-induced cardiac fibroblast activation by partially regulating the TGF-ß1/SMAD2/3 signaling pathway.