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1.
BMC Urol ; 24(1): 102, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702664

ABSTRACT

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.


Subject(s)
Prostatectomy , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Prostatectomy/methods , Middle Aged , Double-Blind Method , Aged , Prostate-Specific Antigen/blood , Soy Foods , Fermentation , Beverages , Isoflavones/therapeutic use , Isoflavones/administration & dosage , Glycine max , Preoperative Care/methods
2.
Medicina (Kaunas) ; 60(4)2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38674244

ABSTRACT

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.


Subject(s)
Dietary Supplements , Glycine max , Hot Flashes , Inositol , Isoflavones , Menopause , Metabolic Syndrome , Polyphenols , Humans , Female , Metabolic Syndrome/drug therapy , Retrospective Studies , Isoflavones/therapeutic use , Isoflavones/pharmacology , Isoflavones/administration & dosage , Middle Aged , Polyphenols/administration & dosage , Polyphenols/therapeutic use , Polyphenols/analysis , Inositol/therapeutic use , Inositol/administration & dosage , Inositol/analysis , Hot Flashes/drug therapy , Menopause/drug effects , Menopause/physiology , Cacao , Metabolome/drug effects
3.
Nutr J ; 23(1): 32, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38454401

ABSTRACT

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.


Subject(s)
Hypertension , Isoflavones , Humans , Blood Pressure , Dietary Supplements , Hypertension/drug therapy , Hypertension/prevention & control , Isoflavones/administration & dosage , Randomized Controlled Trials as Topic
4.
Poult Sci ; 103(5): 103420, 2024 May.
Article in English | MEDLINE | ID: mdl-38518669

ABSTRACT

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.


Subject(s)
Animal Feed , Antioxidants , Chickens , Diet , Dietary Supplements , Isoflavones , Random Allocation , Animals , Chickens/physiology , Isoflavones/pharmacology , Isoflavones/administration & dosage , Female , Animal Feed/analysis , Dietary Supplements/analysis , Antioxidants/metabolism , Diet/veterinary , Intestines/drug effects , Intestines/anatomy & histology , Intestines/physiology , Ovum/drug effects , Ovum/physiology , Dose-Response Relationship, Drug , Reproduction/drug effects
5.
Carcinogenesis ; 45(6): 378-386, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38375679

ABSTRACT

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 (HRQ4vsQ1 = 0.69, 95% CI: 0.50-0.95; P for trend = 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 (HRQ4vsQ1 = 0.68, 95% CI: 0.50-0.94; P for trend = 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.


Subject(s)
Diet , Ovarian Neoplasms , Phytoestrogens , Humans , Female , Phytoestrogens/administration & dosage , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/prevention & control , Ovarian Neoplasms/etiology , Prospective Studies , Middle Aged , Risk Factors , Male , Aged , Lung Neoplasms/epidemiology , Lung Neoplasms/etiology , Lung Neoplasms/prevention & control , Surveys and Questionnaires , Isoflavones/administration & dosage , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/etiology , Colorectal Neoplasms/prevention & control , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/etiology
6.
Poult Sci ; 103(1): 103281, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37992616

ABSTRACT

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.


Subject(s)
Chickens , Isoflavones , Liver , Salmonella Infections, Animal , Animals , Anti-Bacterial Agents/metabolism , Biomarkers/metabolism , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/microbiology , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/veterinary , Chickens/metabolism , Chickens/microbiology , Liver/drug effects , Liver/metabolism , Liver/microbiology , Liver Neoplasms/metabolism , Liver Neoplasms/microbiology , Liver Neoplasms/pathology , Liver Neoplasms/veterinary , Oxidative Stress , Proteomics , Salmonella/drug effects , Food Safety , Salmonella Infections, Animal/complications , Salmonella Infections, Animal/drug therapy , Salmonella Infections, Animal/microbiology , Isoflavones/administration & dosage
7.
Naunyn Schmiedebergs Arch Pharmacol ; 397(7): 4871-4881, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38159158

ABSTRACT

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.


Subject(s)
Apoptosis , Carcinoma, Non-Small-Cell Lung , Cisplatin , Drug Synergism , Isoflavones , Lung Neoplasms , Humans , Cisplatin/pharmacology , Cisplatin/administration & dosage , A549 Cells , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Isoflavones/pharmacology , Isoflavones/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Apoptosis/drug effects , Nanoparticles , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Suspensions , Oxidative Stress/drug effects , Cell Survival/drug effects , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase 9/genetics
8.
Nanomedicine ; 52: 102696, 2023 08.
Article in English | MEDLINE | ID: mdl-37394108

ABSTRACT

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.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Neuropathies , Drug Carriers , E-Selectin , Isoflavones , Hydrogen-Ion Concentration , E-Selectin/metabolism , Micelles , Diabetic Neuropathies/drug therapy , Isoflavones/administration & dosage , Angelica sinensis/chemistry , Astragalus Plant/chemistry , Polysaccharides/chemistry , Kidney , Inflammation/drug therapy , Ibuprofen/chemistry , Sialic Acids/chemistry , Protein Binding , Diabetes Mellitus, Experimental/chemically induced , Streptozocin , Animals , Mice , Male , Mice, Inbred C57BL
9.
Eur J Pharmacol ; 919: 174805, 2022 Mar 15.
Article in English | MEDLINE | ID: mdl-35151651

ABSTRACT

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.


Subject(s)
Cardiovascular Diseases/drug therapy , Fibroblasts/drug effects , Growth Inhibitors/pharmacology , Isoflavones/pharmacology , Myocardium/pathology , Animals , Cardiovascular Diseases/physiopathology , Disease Models, Animal , Dose-Response Relationship, Drug , Fibrosis , Growth Inhibitors/administration & dosage , Growth Inhibitors/therapeutic use , Humans , Isoflavones/administration & dosage , Isoflavones/therapeutic use , Male , Mice, Inbred C57BL , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Smad2 Protein/metabolism , Transforming Growth Factor beta1/metabolism
10.
Alcohol Clin Exp Res ; 46(1): 6-12, 2022 01.
Article in English | MEDLINE | ID: mdl-34779005

ABSTRACT

Standard laboratory diets used have similar concentrations of proteins, carbohydrates and fat, but the concentration of some micronutrients can vary considerably. For example, the concentration of isoflavones can vary between 20 mg and 600 mg per gram of diet. Exposure to different concentrations of isoflavones interacts with alcohol (EtOH) intake, thereby influencing the results of alcohol research. In this mini-review, we describe correlations between isoflavone concentrations and alcohol intake based on data from previously published work. Although the administration of low doses of isoflavones can decrease alcohol intake in rats, there is a positive correlation between the isoflavone content in diets and alcohol intake in mice. This interaction seems to depend on the dose, route of administration, and time of exposure to isoflavones and may be related to specific neurobiological mechanisms. The literature also indicates that isoflavones can interact with some of alcohol's molecular targets and with neural pathways crucial to the alcohol reward process. Given these findings, more attention should be given to the different types of laboratory diets used in alcohol studies to allow better comparison and replication of animal research.


Subject(s)
Animals, Laboratory/physiology , Diet/veterinary , Ethanol/administration & dosage , Isoflavones/administration & dosage , Alcohol Drinking , Animals , Cricetinae , Drug Interactions , Female , Food , Male , Mice , Models, Animal , Rats , Species Specificity
11.
Nutrients ; 13(11)2021 Oct 24.
Article in English | MEDLINE | ID: mdl-34836015

ABSTRACT

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Recently, various dietary interventions have been used extensively as a novel therapy against PCOS. In the present study, we show that soy isoflavone metabolites and resistant starch, together with gut microbiota modulations, were successful in decreasing the severity of PCOS-like reproductive features while increasing the expression of gut barrier markers and butyric acid in the gut. In the letrozole-induced PCOS model rats, the intake of both 0.05% soy isoflavones and 11% resistant starch, even with letrozole treatment, reduced the severity of menstrual irregularity and polycystic ovaries with a high concentration of soy isoflavones and equol in plasma. Antibiotic cocktail treatment suppressed soy isoflavone metabolism in the gut and showed no considerable effects on reducing the PCOS-like symptoms. The mRNA expression level of occludin significantly increased with soy isoflavone and resistant starch combined treatment. Bacterial genera such as Blautia, Dorea and Clostridium were positively correlated with menstrual irregularity under resistant starch intake. Moreover, the concentration of butyric acid was elevated by resistant starch intake. In conclusion, we propose that both dietary interventions and gut microbiota modulations could be effectively used in reducing the severity of PCOS reproductive features.


Subject(s)
Gastrointestinal Microbiome , Isoflavones/administration & dosage , Polycystic Ovary Syndrome/microbiology , Polycystic Ovary Syndrome/therapy , Resistant Starch/administration & dosage , Animals , Anti-Bacterial Agents , Biomarkers/analysis , Butyric Acid/metabolism , Disease Models, Animal , Equol/blood , Female , Isoflavones/blood , Letrozole , Polycystic Ovary Syndrome/chemically induced , Rats , Severity of Illness Index , Soy Foods
12.
Drug Deliv ; 28(1): 2198-2204, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34662253

ABSTRACT

BACKGROUND: Myocardial infarction (MI) is one of the most common ischemic heart diseases. It is very essential to explore new types of cardioprotective drugs delivery systems in this area. OBJECTIVE: The aim of the present study was to investigate the protective effect of baicalin (BA) and puerarin (PU) against acute MI rat models. BA and PU co-loaded nanoparticulate system were developed to improve bioavailability of the drugs, to prolong retention time in vivo and to enhance the protective effect. METHODS: In the present study, ANP and TPP contained ligands were synthesized. ANP/TPP-BN-LPNs were prepared and its physico-chemical properties were evaluated. The MI therapy efficiency of ANP/TPP-BN-LPNs was assessed in rats after intravenous injection. Single ligand contained LPNs, no ligand contained LPNs, and BN solution formulations were also prepared and used for the comparison. RESULTS: ANP/TPP-BN-LPNs were uniform and spheroidal particles. The size of ANP/TPP-BN-LPNs was 98.5 ± 2.9 nm, with a zeta potential of -19.5 ± 1.9 mV. The dual ligands modified LPNs exhibited significantly improved therapeutic efficiency compared with the single ligand modified LPNs and other systems. In vivo infarct therapy studies in rats proved that ANP/TPP-BN-LPNs were a promising system for efficient delivery of cardiovascular drugs for the treatment of cardiovascular diseases. CONCLUSIONS: ANP/TPP-BN-LPNs could be used as a long-circulating and heart-targeting drug delivery system.


Subject(s)
Atrial Natriuretic Factor/pharmacology , Flavonoids/pharmacology , Myocardial Infarction/drug therapy , Nanoparticles/chemistry , Animals , Atrial Natriuretic Factor/administration & dosage , Atrial Natriuretic Factor/pharmacokinetics , Chemistry, Pharmaceutical , Drug Carriers/chemistry , Flavonoids/administration & dosage , Flavonoids/pharmacokinetics , Human Umbilical Vein Endothelial Cells , Humans , Isoflavones/administration & dosage , Isoflavones/pharmacology , Ligands , Male , Muscle Cells , Organophosphorus Compounds/chemistry , Particle Size , Rats , Rats, Sprague-Dawley , Surface Properties
13.
Basic Clin Pharmacol Toxicol ; 129(6): 437-449, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34478607

ABSTRACT

Methylophiopogonanone A (MOA) is an abundant homoisoflavonoid in the Chinese herb Ophiopogonis Radix. Recent investigations revealed that MOA inhibited several human cytochrome P450 enzymes (CYPs) and stimulated OATP1B1. However, the inhibitory effects of MOA on phase II drug-metabolizing enzymes, such as human UDP-glucuronosyltransferases (hUGTs), have not been well investigated. Herein, the inhibition potentials of MOA on hUGTs were assessed. The results clearly demonstrated that MOA dose-dependently inhibited all tested hUGTs including UGT1A1 (IC50 = 1.23 µM), one of the most important detoxification enzymes in humans. Further investigations showed that MOA strongly inhibited UGT1A1-catalysed NHPH-O-glucuronidation in a range of biological settings including hUGT1A1, human liver microsomes (HLM) and HeLa cells overexpressing UGT1A1. Inhibition kinetic analyses demonstrated that MOA competitively inhibited UGT1A1-catalysed NHPH-O-glucuronidation in both hUGT1A1 and HLM, with Ki values of 0.52 and 1.22 µM, respectively. Collectively, our findings expanded knowledge of the interactions between MOA and human drug-metabolizing enzymes, which would be very helpful for guiding the use of MOA-related herbal products in clinical settings.


Subject(s)
Benzodioxoles/pharmacology , Enzyme Inhibitors/pharmacology , Glucuronosyltransferase/antagonists & inhibitors , Herb-Drug Interactions , Isoflavones/pharmacology , Benzodioxoles/administration & dosage , Dose-Response Relationship, Drug , Enzyme Inhibitors/administration & dosage , HeLa Cells , Humans , Inhibitory Concentration 50 , Isoflavones/administration & dosage , Microsomes, Liver/enzymology
14.
Nutrients ; 13(8)2021 Aug 06.
Article in English | MEDLINE | ID: mdl-34444874

ABSTRACT

This study was designed to examine the association of soy isoflavones (SI) intake with different body measurements indicative of obesity in Chinese adults of Shanghai, a population consuming foods rich in SI. This study used baseline data from the Shanghai Gaofeng cohort study. SI intake was measured by using a self-reported food frequency questionnaire (FFQ). A restricted cubic spline (RCS) was performed to examine the possible nonlinear relationship of SI intake with obesity. A logistic regression model was applied to estimate the odds ratios (OR) and 95% confidence interval (CI). Compared with the lowest tertile group of SI intake, the highest tertile group had a lower prevalence of obesity and central obesity. The OR for overall obesity was 0.91 (95% CI: 0.85, 0.98) in the highest versus the lowest SI tertile group; the associations differed by sex and menopausal status. A negative association was also observed between SI intake and central obesity, and a significant modifying effect of sex was found on the association. No significant interactions were observed between SI intake and physical activity (PA) levels. Our results suggest that Chinese adults with higher dietary intake of SI may be less likely to be obese, particularly for postmenopausal women.


Subject(s)
Diet , Isoflavones/administration & dosage , Obesity/epidemiology , Soy Foods , Adult , Aged , China/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Obesity/diagnosis , Obesity/prevention & control , Postmenopause , Protective Factors , Risk Assessment , Risk Factors , Sex Factors , Young Adult
15.
Nutrients ; 13(7)2021 Jul 05.
Article in English | MEDLINE | ID: mdl-34371819

ABSTRACT

Epidemiological studies suggest that high intake of soy isoflavones may protect against breast cancer, but causal relationships can only be established by experimental trials. Thus, we aimed to provide a systematic review of randomized controlled trials (RCTs) on the effect of an isoflavone intake on risk factors of breast cancer in healthy subjects. After a systematic literature search in PubMed, 18 different RCTs with pre- and/or postmenopausal women were included and investigated for details according to the PRISMA guideline. In these studies, isoflavones were provided by soy food or supplements in amounts between 36.5-235 mg/d for a period of 1-36 months. Breast density, estrogens including precursors, metabolites, estrogen response such as length of menstrual cycle, and markers of proliferation and inflammation were considered. However, in most studies, differences were not detectable between isoflavone and control/placebo treatment despite a good adherence to isoflavone treatment, irrespective of the kind of intervention, the dose of isoflavones used, and the duration of isoflavone treatment. However, the lack of significant changes in most studies does not prove the lack of effects as a sample size calculation was often missing. Taking into account the risk of bias and methodological limitations, there is little evidence that isoflavone treatment modulates risk factors of breast cancer in pre- and postmenopausal women. Future studies should calculate the sample size to detect possible effects and consider methodological details to improve the study quality.


Subject(s)
Breast Neoplasms/prevention & control , Diet/methods , Eating/physiology , Isoflavones/administration & dosage , Soy Foods , Adult , Aged , Bias , Breast Neoplasms/etiology , Diet/adverse effects , Dietary Supplements , Female , Humans , Middle Aged , Postmenopause/blood , Premenopause/blood , Randomized Controlled Trials as Topic , Risk Factors
16.
Nutrients ; 13(8)2021 Jul 24.
Article in English | MEDLINE | ID: mdl-34444691

ABSTRACT

The aim of the report was to evaluate the impact of soy protein containing isoflavones and soy isoflavones extract on lipid profile in postmenopausal women, as compared with placebo or protein of milk, casein or isolated soy protein with or without trace isoflavone content. We used the following databases: MEDLINE (PubMed), EMBASE and the Cochrane Library. Quantitative data synthesis was performed by applying a random-effects model. Subgroup analysis and meta-regression were performed to assess the modifiers of treatment response. In total, in the analysis studies, 2305 postmenopausal women took part. Changes in the lipid profile showed statistically significant decreases of total cholesterol by -0.12 (95% CI: -0.21, -0.03) mmol/L, -4.64 (95% CI: -8.12, -1.16) mg/dL, p = 0.01 and increased HDL-cholesterol by 0.03 (95% CI: 0.00, 0.06) mmol/L, 1.15 (95% CI: 0.00, 1.93) mg/dL, p = 0.05, as well as in LDL-cholesterol -0.05 (95% CI: -0.11, 0.01) mmol/L, -1.93 (95% CI: -4.25, 0.39) mg/dL, p = 0.08 and triacylglycerols -0.07 (95% CI: -0.14, 0.00) mmol/L, -6.123 (95% CI: -12.25, 0.00) mg/dL, p = 0.06. Our results suggests that soy and its isoflavones can be effective in correction changes in lipid metabolism in postmenopausal women and may favorably influence in preventing cardiovascular events.


Subject(s)
Cardiovascular Diseases/prevention & control , Lipids/blood , Plant Extracts/administration & dosage , Postmenopause/blood , Soybean Proteins/administration & dosage , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Female , Humans , Isoflavones/administration & dosage , Lipid Metabolism/drug effects , Middle Aged , Randomized Controlled Trials as Topic , Triglycerides/blood
17.
Drug Deliv ; 28(1): 1539-1547, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34282705

ABSTRACT

Chemotherapy with combination drugs has become one of the most commonly used cancer prevention treatments, with positive clinical results. The goal of this study was to develop compostable polymeric nanomaterials (NMs) for the delivery of puerarin (PRN) and 5-fluorouracil (5FU), as well as to investigate the anticancer activity of the drug delivery system (PRN-5FU NMs) against in vitro and in vivo lung cancer cells. Since double antitumor drugs PRN and 5FU are insufficiently compressed in polymer-based bio-degradable nanoparticles, encapsulation of PRN and 5FU antitumor drugs were co-encapsulated with polyethylene glycol and polylactidecoglycolide nanoparticles (NMs) is efficient. The arrangement of PRN NMs, 5FU NMs, and PRN-5FU NMs, as well as the nanoparticles shape and scale, were studied using transmission electron microscopy (TEM). 5FU-PRN NMs triggered apoptosis in lung carcinoma cell lines such as HEL-299 and A549 in vitro. Acridine orange/ethidium bromide (AO/EB) and nuclear damaging staining techniques were used to observe morphologies and cell death. The mechanistic analysis of apoptosis was also confirmed by flow cytometry analysis using dual staining. When compared to free anticancer products, the hemolysis analysis findings of the 5FU-PRN NMs showed excellent biocompatibility. Taken together the advantages, this combination drug conveyance strategy exposed that 5FU-PRN NMs could have a significant promising to improve the effectiveness of lung cancer cells.


Subject(s)
Antineoplastic Agents/administration & dosage , Fluorouracil/administration & dosage , Isoflavones/administration & dosage , Lung Neoplasms/drug therapy , Nanoparticles/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Chemistry, Pharmaceutical , Drug Carriers , Drug Combinations , Drug Liberation , Fluorouracil/pharmacology , Humans , Isoflavones/pharmacology , Polyethylene Glycols/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry
18.
Food Funct ; 12(17): 7997-8006, 2021 Sep 07.
Article in English | MEDLINE | ID: mdl-34263280

ABSTRACT

BACKGROUND AND OBJECTIVE: soy protein and soy isoflavones have been suggested to be associated with improved cardiovascular risk factors (e.g., lipid profiles and uric acid (UA)), but few studies have been conducted among women with impaired glucose regulation (IGR). This study is aimed to evaluate the effect of isolated daidzein and genistein on lipid profiles, high sensitive C-reactive protein (hs-CRP), and uric acid (UA) among Chinese women with IGR. METHODS AND RESULTS: this randomized, double-blind, and placebo-controlled trial was conducted in 165 Chinese women aged 30-70 years with IGR. Participants were randomly assigned to one of the three groups: 0 mg of daidzein and genistein with 10 g soy protein (placebo group), 50 mg of daidzein with 10 g soy protein (daidzein group), or 50 mg of genistein with 10 g soy protein (genistein group) supplementation for 24 weeks. Fasting serum total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), lipoprotein a (LP (a)), hs-CRP, and UA were assessed at baseline, 12, and 24 weeks after intervention. The results showed no significant differences in the changes (%) of TC, TG, HDL-C, LDL-C, LP (a), hs-CRP, and UA between the three treatment groups at weeks 12 or 24 (all P > 0.05). CONCLUSION: neither isolated daidzein nor genistein had a significant effect on cardiovascular health in Chinese women with IGR.


Subject(s)
Cardiovascular Diseases/metabolism , Genistein/administration & dosage , Glucose/metabolism , Isoflavones/administration & dosage , Adult , Aged , Biomarkers/blood , C-Reactive Protein/metabolism , Cardiovascular Diseases/drug therapy , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Double-Blind Method , Female , Humans , Middle Aged , Triglycerides/blood
19.
Neurotox Res ; 39(5): 1651-1664, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34258694

ABSTRACT

Astrocytes are crucial for the maintenance of brain homeostasis by actively participating in the metabolism of glucose, which is the main energy substrate for the central nervous system (CNS), in addition to other supportive functions. More specifically, astrocytes support neurons through the metabolic coupling of synaptic activity and glucose utilization. As such, diabetes mellitus (DM) and consequent glucose metabolism disorders induce astrocyte damage, affecting CNS functionality. Glioprotective molecules can promote protection by improving glial functions and avoiding toxicity in different pathological conditions, including DM. Therefore, this review discusses specific pathomechanisms associated with DM/glucose metabolism disorder-induced gliotoxicity, namely astrocyte metabolism, redox homeostasis/mitochondrial activity, inflammation, and glial signaling pathways. Studies investigating natural products as potential glioprotective strategies against these deleterious effects of DM/glucose metabolism disorders are also reviewed herein. These products include carotenoids, catechins, isoflavones, lipoic acid, polysaccharides, resveratrol, and sulforaphane.


Subject(s)
Astrocytes/drug effects , Brain/metabolism , Diabetes Mellitus/metabolism , Glucose/antagonists & inhibitors , Oxidative Stress/drug effects , Animals , Astrocytes/metabolism , Brain/drug effects , Diabetes Mellitus/drug therapy , Glucose/metabolism , Humans , Isoflavones/administration & dosage , Oxidative Stress/physiology , Reactive Oxygen Species/antagonists & inhibitors , Reactive Oxygen Species/metabolism , Resveratrol/administration & dosage , Thioctic Acid/administration & dosage
20.
Food Funct ; 12(17): 7607-7618, 2021 Sep 07.
Article in English | MEDLINE | ID: mdl-34236368

ABSTRACT

Diabetic nephropathy (DN) is a microvascular complication that is becoming a worldwide public health concern. The aim of this study was to assess the effects of dietary soy isoflavone intervention on renal function and metabolic syndrome markers in DN patients. Seven databases including Medline, the Cochrane Central Register of Controlled Trials, Science Direct, Web of Science, Embase, China National Knowledge Infrastructure, and WanFang were searched for controlled trials that assessed the effects of soy isoflavone treatment in DN patients. Finally, a total of 141 patients from 7 randomized controlled trials were included. The meta-analysis showed that dietary soy isoflavones significantly decreased 24-hour urine protein, C-reactive protein (CRP), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose (FBG) in DN patients. The standard mean difference was -2.58 (95% CI: -3.94, -1.22; P = 0.0002) for 24-hour urine protein, -0.67 (95% CI: -0.94, -0.41; P < 0.00001) for BUN, -6.16 (95% CI: -9.02, -3.31; P < 0.0001) for CRP, -0.58 (95% CI: -0.83, -0.33; P < 0.00001) for TC, -0.41 (95% CI: -0.66, -0.16; P < 0.00001) for TG, -0.68 (95% CI: -0.94, -0.42; P < 0.00001) for LDL-C, and -0.39 (95% CI: -0.68, -0.10; P = 0.008) for FBG. Therefore, soy isoflavones may ameliorate DN by significantly decreasing 24-hour urine protein, BUN, CRP, TC, TG, LDL-C, and FBG.


Subject(s)
Diabetic Nephropathies/drug therapy , Isoflavones/administration & dosage , Adult , Aged , Blood Glucose/metabolism , C-Reactive Protein/metabolism , Cholesterol, LDL/metabolism , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/physiopathology , Dietary Supplements/analysis , Female , Humans , Male , Middle Aged , Randomized Controlled Trials as Topic , Triglycerides/metabolism
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