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1.
Zhongguo Zhong Yao Za Zhi ; 46(17): 4410-4416, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34581044

RESUMO

This study was mainly based on the compatibility of Puerariae Lobatae Radix and Chuanxiong Rhizoma to prepare submicron emulsion and evaluated its physical and pharmaceutical properties. Firstly, pseudo-ternary phase diagrams were drawn by dripping method which took Chuanxiong oil as the oil phase and the area of microemulsion region as the index. On this basis, suitable emulsifier and co-emulsifier were screened for the preparation of Chuanxiong oil submicron emulsion. Then, the formula realizing the largest oil loading was selected. Finally, puerarin substituted part of emulsifier and co-emulsifier to lower their content, so as to form puerarin-Chuanxiong oil submicron emulsion featuring the combination of medicine and adjuvant. Its particle size, zeta potential, centrifugal stability and storage stability were determined, and the in vitro drug release behavior was investigated by dialysis bag method, based on which the quality of the as-prepared submicron emulsion was evaluated comprehensively. The proposed method was proved feasible for the preparation of Chuanxiong oil submicron emulsion, which adopted polyoxyethylene castor oil(EL-40) as the emulsifier and was free from co-emulsifier. The formula of the maximum oil loading was found as Chuanxiong oil∶EL-40∶water 3∶7∶90. Further, puera-rin successfully replaced up to 10% of the emulsifier in submicron emulsion. Eventually, the optimal drug-loading formula was determined as puerarin∶Chuanxiong oil∶EL-40∶water 7∶30∶63∶900. The quality evaluation results of the as-prepared submicron emulsion demonstrated that the average emulsion droplet size was 333.9 nm, the PDI 0.26, and the zeta potential-10.12 mV. The submicron emulsion had a good centrifugal stability and did not present any instable phenomena such as delamination and precipitation during its standing still for 50 days. The evaluation of in vitro drug release behavior indicated that the submicron emulsion was capable of releasing the drug completely. The puerarin-chuanxiong oil submicron emulsion prepared in this study possessed a stable quality and to some extent increased the solubility of puerarin along with a sustained-release effect. This study provided ideas for the clinical application of puerarin.


Assuntos
Isoflavonas , Emulsões , Tamanho da Partícula , Solubilidade
2.
J Int Med Res ; 49(9): 3000605211040762, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34590923

RESUMO

OBJECTIVE: Previous investigations indicated the anticancer activity of puerarin. The current study aimed to evaluate the effect and molecular mechanisms of puerarin in chemotherapy-resistant ovarian cancer cells. METHODS: We examined the effects of puerarin in platinum-resistant epithelial ovarian cancer cells in vitro and in vivo. We also analyzed the molecular mechanism underlying Wnt/ß-catenin inhibition and sirtuin 1 (SIRT1) regulation following puerarin treatment. RESULTS: Our study demonstrated that puerarin effectively inhibited cell growth in vitro and in vivo by increasing apoptosis in ovarian cancer cells. More importantly, puerarin sensitized cisplatin-resistant ovarian cancer cells to chemotherapy. Puerarin treatment decreased SIRT1 expression, which attenuated the nuclear accumulation of ß-catenin to inhibit Wnt/ß-catenin signaling. In addition, SIRT1 overexpression diminished the effects of puerarin treatment on cisplatin-resistant ovarian cancer cells. Further analysis supported SIRT1/ß-catenin expression as a candidate biomarker for the disease progression of epithelial ovarian cancer. CONCLUSIONS: Puerarin increased the apoptosis of platinum-resistant ovarian cancer cells. The mechanism is partly related to the downregulation of SIRT1 and subsequent inhibition of Wnt/ß-catenin signaling.


Assuntos
Neoplasias Ovarianas , Sirtuína 1 , Apoptose , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Isoflavonas , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Sirtuína 1/genética , beta Catenina/genética
3.
Chin J Dent Res ; 24(3): 153-158, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491009

RESUMO

OBJECTIVE: To investigate the effects of ipriflavone (IPF), a synthetic isoflavone plant oestrogen with a structure similar to that of oestradiol, on the osteogenic differentiation of bone mesenchymal stem cells (BMSCs). METHODS: BMSCs were derived from ovariectomised rats (rBMSCs-OVX) and then induced with or without IPF. Cell cytotoxicity, mineralisation in vitro and osteoblast-specific gene expression of BMSCs were studied. RESULTS: IPF at a concentration of 10-8, 10-7 and 10-6 mol/l exhibited no cytotoxic effect on the proliferation of BMSCs but increased alkaline phosphatase activity and osteoblast-specific gene expression. CONCLUSION: IPF enhances osteogenic differentiation of rBMSCs-OVX partly in vitro, thus its use offers a potential strategy for the treatment of osteoporosis.


Assuntos
Isoflavonas , Células-Tronco Mesenquimais , Osteoporose , Animais , Células Cultivadas , Isoflavonas/farmacologia , Osteogênese , Osteoporose/tratamento farmacológico , Ratos
4.
Nutrients ; 13(8)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34444874

RESUMO

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.


Assuntos
Dieta , Isoflavonas/administração & dosagem , Obesidade/epidemiologia , Alimentos de Soja , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/prevenção & controle , Pós-Menopausa , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores Sexuais , Adulto Jovem
5.
Nat Prod Res ; 35(16): 2744-2747, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34414847

RESUMO

The first phytochemical investigation of the flowers of Millettia dura resulted in the isolation of seven isoflavones, a flavonol and a chalcone. Eleven isoflavones and a flavonol isolated from various plant parts from this plant were tested for cytotoxicity against a panel of cell lines, and six of these showed good activity with IC50 values of 6-14 µM. Durmillone was the most active with IC50 values of 6.6 µM against A549 adenocarcinomic human alveolar basal epithelial cancer cell line with low cytotoxicity against the non-cancerous cell lines BEAS-2B (IC50 = 58.4 µM), LO2 hepatocytes (IC50 78.7 µM) and CCD19Lu fibroblasts (IC50 >100 µM).


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Isoflavonas , Millettia , Células A549 , Antineoplásicos Fitogênicos/isolamento & purificação , Humanos , Isoflavonas/isolamento & purificação , Isoflavonas/farmacologia , Millettia/química , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
6.
Toxicol Appl Pharmacol ; 427: 115668, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34358556

RESUMO

Pharmacological postconditioning (PPC), drug intervention before or during the early minutes of reperfusion, could stimulate cardioprotection as ischemic postconditioning. In this study, we examined whether PPC with sappanone A (SA), a homoisoflavanone with potent antioxidant and anti-inflammatory activity, has a protective effect on myocardial ischemia reperfusion injury (MIRI), and explored the underlying mechanism. A MIRI model was established using the Langendorff method. After 30 min of ischemia, isolated rat hearts were treated with SA at the onset of reperfusion to stimulate PPC. The changes in myocardial infarct size, mitochondrial function, mitochondrial biogenesis, mitophagy, and mitochondrial fission and fusion were detected. The results showed that SA postconditioning decreased the myocardial infarct size, inhibited the release of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and cardiac troponin (cTnI), as well as improved cardiac function, enhanced myocardial ATP content and mitochondrial complex activity, and prevented the loss of mitochondrial membrane potential and opening of mitochondrial permeability transition pore (mPTP). Mechanistically, we found that SA was an AMP-activated protein kinase (AMPK) activator, and SA postconditioning could facilitate mitochondrial biogenesis by increasing mitochondrial DNA (mtDNA) copy number and the expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α). In addition, it balanced mitochondrial dynamics by decreasing fission and increasing fusion, and enhanced mitophagy in an AMPK-dependent manner. Moreover, AMPK silencing abolished the cardioprotection of SA postconditioning. Collectively, our study demonstrated that SA postconditioning ameliorated MIRI and mitochondrial dysfunction by regulation of mitochondrial quality control via activating AMPK. This finding provides a new insight into pharmacological action and clinical use of SA.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Pós-Condicionamento Isquêmico/métodos , Isoflavonas/farmacologia , Mitocôndrias Cardíacas/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Animais , Relação Dose-Resposta a Droga , Isoflavonas/uso terapêutico , Preparação de Coração Isolado/métodos , Masculino , Mitocôndrias Cardíacas/efeitos dos fármacos , Ratos , Ratos Wistar
7.
Molecules ; 26(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34443497

RESUMO

Soy diet is thought to help prevent cardiovascular diseases in humans. Isoflavone, which is abundant in soybean and other legumes, has been reported to possess antiplatelet activity and potential antithrombotic effect. Our study aims to elucidate the potential target of soy isoflavone in platelet. The anti-thrombosis formation effect of genistein and daidzein was evaluated in ex vivo perfusion chamber model under low (300 s-1) and high (1800 s-1) shear forces. The effect of genistein and daidzein on platelet aggregation and spreading was evaluated with platelets from both wildtype and GPIbα deficient mice. The interaction of these soy isoflavone with 14-3-3ζ was detected by surface plasmon resonance (SPR) and co-immunoprecipitation, and the effect of αIIbß3-mediated outside-in signaling transduction was evaluated by western blot. We found both genistein and daidzein showed inhibitory effect on thrombosis formation in perfusion chamber, especially under high shear force (1800 s-1). These soy isoflavone interact with 14-3-3ζ and inhibited both GPIb-IX and αIIbß3-mediated platelet aggregation, integrin-mediated platelet spreading and outside-in signaling transduction. Our findings indicate that 14-3-3ζ is a novel target of genistein and daidzein. 14-3-3ζ, an adaptor protein that regulates both GPIb-IX and αIIbß3-mediated platelet activation is involved in soy isoflavone mediated platelet inhibition.


Assuntos
Proteínas 14-3-3/metabolismo , Plaquetas/metabolismo , Isoflavonas/farmacologia , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Transdução de Sinais , Soja/química , Animais , Fibrinogênio/metabolismo , Genisteína/química , Genisteína/farmacologia , Proteínas Imobilizadas/metabolismo , Isoflavonas/química , Masculino , Camundongos Endogâmicos C57BL , Agregação Plaquetária/efeitos dos fármacos , Trombose/patologia
8.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3311-3318, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396750

RESUMO

The effects of water regulation on the biosynthesis of calycosin-7-O-ß-D-glucoside in 2-year-old Astragalus membranaceus var. mongholicus were studied,and the mechanism was explained from the aspects of key enzyme gene expression and antioxidant enzyme system. The content of calycosin-7-O-ß-D-glucoside was determined by HPLC,and the expression levels of six key enzyme genes( PAL,4 CL,CHS,CHI,IFS,13'H) in the synthesis pathway were analyzed by q RT-PCR. The activities of protective enzymes and contents of osmoregulation substances and malondialdehyde were also determined. In the water deficit group,the maximum concentration of calycosin-7-O-ß-D-glucoside was 0. 49 mg·g-1 on the 24 th day of treatment. In the whole water regulation,the water deficit group outweighed the water adequate group in osmoregulation substance and MDA contents. The activities of A. membranaceus var.mongholicus antioxidant enzymes SOD,POD,and CAT increased during the initial period of water regulation,but decreased with time.The expression of PAL,CHS,and 13'H in the water deficit group was at a low level,and the 4 CL had active expression,slightly lower than that in the water adequate group. The expression of CHI and IFS elevated rapidly when water deficit occurred. Correlation analysis showed that the content of calycosin-7-O-ß-D-glucoside was positively correlated with CHI expression( P<0. 01) and IFS expression( P<0. 05). Therefore,water regulation can change the accumulation pattern of calycosin-7-O-ß-D-glucoside,and water deficit may be an effective way to increase its content. CHI and IFS are the key genes in response to water deficit.


Assuntos
Astragalus propinquus , Isoflavonas , Astragalus propinquus/genética , Vias Biossintéticas , Glucosídeos , Água
9.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360871

RESUMO

The root of Pueraria lobata (Willd.) is a widely used herbal medicine worldwide, whereas the stem of the plant is discarded or used as feed for livestock. To reuse and exploit the stem of P. lobata as a resource, we investigated its potential as a skin-whitening agent. We found that the developed, enriched P. lobata stem (PLS) extract significantly inhibited melanin production in the 3-isobutyl-1-methylxanthine-induced B16/F10 cells at a concentration of 50 µg/mL. To further confirm the mechanism of the antimelanogenic effect of the enriched PLS extracts, we examined the mRNA expression of tyrosinase, which was suppressed by the extracts. To standardize and implement effective quality control of the enriched PLS extracts, its major chemical constituents were identified by high-performance liquid chromatography-photodiode array-electrospray ionization-mass spectrometry. In total, 12 constituents were identified. In silico analysis showed that the main constituents, puerarin and daidzin, had excellent binding affinities for human tyrosinase. Collectively, our results suggest that the PLS extracts could be used as anti-pigmentation agents.


Assuntos
Melaninas/biossíntese , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Caules de Planta/química , Pueraria/química , Preparações Clareadoras de Pele/farmacologia , Linhagem Celular Tumoral , Humanos , Isoflavonas/farmacologia , Melanoma Experimental , Monofenol Mono-Oxigenase/metabolismo
10.
Nutrients ; 13(7)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34371819

RESUMO

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.


Assuntos
Neoplasias da Mama/prevenção & controle , Dieta/métodos , Ingestão de Alimentos/fisiologia , Isoflavonas/administração & dosagem , Alimentos de Soja , Adulto , Idoso , Viés , Neoplasias da Mama/etiologia , Dieta/efeitos adversos , Suplementos Nutricionais , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Pré-Menopausa/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
11.
Molecules ; 26(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34361668

RESUMO

Despite many advances in therapy, glioblastoma (GB) is still characterized by its poor prognosis. The main reason for this is unsuccessful treatment, which slightly extends the duration of remission; thus, new regimens are needed. One of many types of chemotherapeutics that are being investigated in this field is topoisomerase inhibitors, mainly in combination therapy with other drugs. On the other hand, the search for new anti-cancer substances continues. Neobavaisoflavone (NBIF) is a natural compound isolated from Psoralea corylifolia L., which possesses anti-oxidant, anti-inflammatory, and anti-cancer properties. The aim of this study was to evaluate the effect of NBIF in human U-87 MG glioblastoma cells in comparison to normal human NHA astrocytes, and to examine if it influences the activity of irinotecan, etoposide, and doxorubicin in this in vitro model. We demonstrated that NBIF decreases U-87 MG cells viability in a dose-dependent manner. Furthermore, we found that it inhibits cell growth and causes glutathione (GSH) depletion more intensely in U-87 MG cells than in astrocytes. This study also provides, for the first time, evidence of the potentialization of the doxorubicin effect by NBIF, which was shown by the reduction in the viability in U-87 MG cells.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Neoplasias Encefálicas/metabolismo , Doxorrubicina/farmacologia , Etoposídeo/farmacologia , Glioblastoma/metabolismo , Irinotecano/farmacologia , Isoflavonas/farmacologia , Extratos Vegetais/farmacologia , Psoralea/química , Inibidores da Topoisomerase II/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Glioblastoma/patologia , Glutationa/metabolismo , Humanos , Transdução de Sinais/efeitos dos fármacos
12.
Nutrients ; 13(8)2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34444691

RESUMO

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.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Lipídeos/sangue , Extratos Vegetais/administração & dosagem , Pós-Menopausa/sangue , Proteínas de Soja/administração & dosagem , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Isoflavonas/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos/sangue
13.
Nutrients ; 13(8)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34444844

RESUMO

The implementation of REGULATION (EC) No 1924/2006 has led to the formation of a list of health claims that can be used in food supplements (EU 432/2012). However, such supplements are often composed of plant preparations with claims omitted from this list. The peculiarity of plants is related to their long history of use, that could allow claims based on traditionally recognized health effects. In addition, the scientific literature has been enriched over the years through clinical studies that have assessed the bioavailability and efficacy of bioactive components, and investigated their mechanisms of action. Based on existing recognized models which aim to classify research according to the level of scientific evidence, Synadiet developed a three-grade model (A, B or C) for assessing plants health claims. In this paper, the applicability of the model is illustrated through an example for which a Grade B health claim attesting the possible contribution of red clover isoflavones to the improvement of blood lipid levels in postmenopausal women has been attributed. The model appears able to be easily extrapolated to claims pertaining to other plants. If adopted by consensus at European level, this model could initiate the implementation of a positive list of health claims on plant preparations.


Assuntos
Suplementos Nutricionais/normas , Análise de Alimentos/métodos , Rotulagem de Alimentos/normas , Preparações de Plantas/normas , Plantas Comestíveis , Adulto , Idoso , Suplementos Nutricionais/análise , Feminino , Rotulagem de Alimentos/legislação & jurisprudência , Humanos , Isoflavonas/análise , Isoflavonas/normas , Legislação sobre Alimentos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Preparações de Plantas/análise , Pós-Menopausa/sangue , Trifolium/química
14.
Nutrients ; 13(8)2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34444848

RESUMO

Flavonoids are a major group of dietary plant polyphenols and have a positive health impact, but their modification and degradation in the human gut is still widely unknown. Due to the rise of metagenome data of the human gut microbiome and the assembly of hundreds of thousands of bacterial metagenome-assembled genomes (MAGs), large-scale screening for potential flavonoid-modifying enzymes of human gut bacteria is now feasible. With sequences of characterized flavonoid-transforming enzymes as queries, the Unified Human Gastrointestinal Protein catalog was analyzed and genes encoding putative flavonoid-modifying enzymes were quantified. The results revealed that flavonoid-modifying enzymes are often encoded in gut bacteria hitherto not considered to modify flavonoids. The enzymes for the physiologically important daidzein-to-equol conversion, well studied in Slackiaisoflavoniconvertens, were encoded only to a minor extent in Slackia MAGs, but were more abundant in Adlercreutzia equolifaciens and an uncharacterized Eggerthellaceae species. In addition, enzymes with a sequence identity of about 35% were encoded in highly abundant MAGs of uncultivated Collinsella species, which suggests a hitherto uncharacterized daidzein-to-equol potential in these bacteria. Of all potential flavonoid modification steps, O-deglycosylation (including derhamnosylation) was by far the most abundant in this analysis. In contrast, enzymes putatively involved in C-deglycosylation were detected less often in human gut bacteria and mainly found in Agathobacter faecis (formerly Roseburia faecis). Homologs to phloretin hydrolase, flavanonol/flavanone-cleaving reductase and flavone reductase were of intermediate abundance (several hundred MAGs) and mainly prevalent in Flavonifractor plautii. This first comprehensive insight into the black box of flavonoid modification in the human gut highlights many hitherto overlooked and uncultured bacterial genera and species as potential key organisms in flavonoid modification. This could lead to a significant contribution to future biochemical-microbiological investigations on gut bacterial flavonoid transformation. In addition, our results are important for individual nutritional recommendations and for biotechnological applications that rely on novel enzymes catalyzing potentially useful flavonoid modification reactions.


Assuntos
Proteínas de Bactérias/metabolismo , Flavonoides/metabolismo , Microbioma Gastrointestinal/fisiologia , Fenômenos Fisiológicos da Nutrição/fisiologia , Simulação por Computador , Equol/metabolismo , Genoma Bacteriano , Humanos , Isoflavonas/metabolismo , Metagenoma , Peptídeo Hidrolases/metabolismo , Proteólise
15.
Biomolecules ; 11(7)2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34356602

RESUMO

Cadmium (Cd) is a potential pathogenic factor in the nervous system associated with various neurodegenerative disorders. Puerarin (Pur) is an isoflavone purified from the Chinese medical herb, kudzu root, and exhibits antioxidant and antiapoptotic properties in the brain. In this study, the detailed mechanisms underlying the neuroprotective potential of Pur against Cd-induced neuronal injury was evaluated for the first time in vivo in a rat model and in vitro using primary rat cerebral cortical neurons. The results of the in vivo experiments showed that Pur ameliorated Cd-induced neuronal injury, reduced Cd levels in the cerebral cortices, and stimulated Cd excretion in Cd-treated rats. We also observed that the administration of Pur rescued Cd-induced oxidative stress, and attenuated Cd-induced apoptosis by concomitantly suppressing both the Fas/FasL and mitochondrial pathways in the cerebral cortical neurons of rats both in vivo and in vitro. Our results demonstrate that Pur exerted its neuroprotective effects by stimulating Cd excretion, ameliorating Cd-induced oxidative stress and apoptosis in rat cerebral cortical neurons.


Assuntos
Apoptose/efeitos dos fármacos , Cádmio , Córtex Cerebral , Isoflavonas/farmacologia , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Cádmio/farmacocinética , Cádmio/toxicidade , Córtex Cerebral/lesões , Córtex Cerebral/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
16.
AAPS PharmSciTech ; 22(6): 217, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34386832

RESUMO

To improve the bioavailability of puerarin in liver, the optimized preparation method of puerarin-PLGA nanoparticles (Pue-PLGA-nps) and the effect of Pue-PLGA-nps on alcoholism mice were studied. The preparation of Pue-PLGA-nps was optimized by the Box-Behnken design and response surface methodology (RSM). To estimate the anti-alcoholism of Pue-PLGA-nps in vivo, drunkenness incubation period and sober time of mice were detected, and Morris water maze (MWM) test was performed. AST, ALT, and SOD were used to determine the damages and oxidative stress in the liver, as well as histopathological observation of the liver. The optimal preparation conditions of Pue-PLGA-nps in RSM were as follows: the drug-material ratio was 1:1.4, the reaction temperature was 65°C, and the reaction time was 13 min. The drug entrapment efficiency of Pue-PLGA-nps was 90.6% and closely up to 98.9% of the standard prediction value. The results in vivo showed that the Pue-PLGA-nps significantly increased the drunkenness incubation period in comparison with the model group and decreased drunkenness sober time and landing time in MWM in comparison with the model group and puerarin group (P<0.05) . The contents of AST and ALT in the liver of Pue-PLGA-nps group were significantly lower than those of model group and Puerarin group (P<0.05), and the activity of SOD in the liver of Pue-PLGA-nps group was higher than that of model group (P<0.05). By histopathological observation, moreover, Pue-PLGA-nps significantly attenuated the impairment of the liver caused by alcoholism. In conclusion, through BBD and RSM, the process conditions of the Pue-PLGA-nps were successfully optimized. The Pue-PLGA-nps exerted higher bioavailability and better effect of anti-alcoholism than puerarin, indicating PLGA nanoparticles could be potential to deliver drug.


Assuntos
Intoxicação Alcoólica , Nanopartículas , Preparações Farmacêuticas , Animais , Portadores de Fármacos , Isoflavonas , Camundongos , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
17.
Artigo em Inglês | MEDLINE | ID: mdl-34444002

RESUMO

The U.S. Hispanic female population has one of the highest breast cancer (BC) incidence and mortality rates, while BC is the leading cause of cancer death in Puerto Rican women. Certain foods may predispose to carcinogenesis. Our previous studies indicate that consuming combined soy isoflavones (genistein, daidzein, and glycitein) promotes tumor metastasis possibly through increased protein synthesis activated by equol, a secondary dietary metabolite. Equol is a bacterial metabolite produced in about 20-60% of the population that harbor and exhibit specific gut microbiota capable of producing it from daidzein. The aim of the current study was to investigate the prevalence of equol production in Puerto Rican women and identify the equol producing microbiota in this understudied population. Herein, we conducted a cross-sectional characterization of equol production in a clinically based sample of eighty healthy 25-50 year old Puerto Rican women. Urine samples were collected and evaluated by GCMS for the presence of soy isoflavones and metabolites to determine the ratio of equol producers to equol non-producers. Furthermore, fecal samples were collected for gut microbiota characterization on a subset of women using next generation sequencing (NGS). We report that 25% of the participants were classified as equol producers. Importantly, the gut microbiota from equol non-producers demonstrated a higher diversity. Our results suggest that healthy women with soy and high dairy consumption with subsequent equol production may result in gut dysbiosis by having reduced quantities (diversity) of healthy bacterial biomarkers, which might be associated to increased diseased outcomes (e.g., cancer, and other diseases).


Assuntos
Equol , Isoflavonas , Adulto , Estudos Transversais , Suplementos Nutricionais , Feminino , Hispano-Americanos , Humanos , Pessoa de Meia-Idade , Pós-Menopausa
18.
Food Res Int ; 147: 110474, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34399471

RESUMO

The effects of enzymatic extraction strategies on extractability, bioconversion, and bioaccessibility of biologically active isoflavone aglycones, total phenolic content, and antioxidant activity of aqueous extracts from full-fat soy flour were evaluated. Protease, tannase, and cellulase enzymes were used individually or in combination. Except for the protease treatment, all enzymatic treatments increased the extraction of biologically active isoflavones (daidzein and genistein) compared with the control. The use of a mixture of protease, tannase, and cellulase resulted in increased extractability and/or bioconversion of aglycones from soy flour, indicating a synergistic effect amongst the enzymes. Daidzein and genistein concentrations increased from 29.0 to 158.2 µg/g and from 27.0 to 156.5 µg/g (compared to the control), respectively. Furthermore, enzymatic extraction followed by in vitro gastrointestinal digestion significantly increased the bioaccessibility of isoflavone aglycones, total phenolic content (by 22-45%), and antioxidant activity (by 15-22%) of the extracts. These results demonstrate that enzyme selection is an efficient strategy to maximize the extraction, bioconversion, and bioaccessibility of bioactive isoflavones from soy flour, which could contribute to health benefits associated with the consumption of soy-rich products.


Assuntos
Isoflavonas , Soja , Digestão , Farinha , Genisteína
19.
Artigo em Inglês | MEDLINE | ID: mdl-34360231

RESUMO

Isoflavones are metabolized by components of the gut microbiota and can also modulate their composition and/or activity. This study aimed to analyze the modifications of the fecal microbial populations and their metabolites in menopausal women under dietary treatment with soy isoflavones for one month. Based on the level of urinary equol, the women had been stratified previously as equol-producers (n = 3) or as equol non-producers (n = 5). The composition of the fecal microbiota was assessed by high-throughput sequencing of 16S rRNA gene amplicons and the changes in fatty acid excretion in feces were analyzed by gas chromatography. A greater proportion of sequence reads of the genus Slackia was detected after isoflavone supplementation. Sequences of members of the family Lachnospiraceae and the genus Pseudoflavonifractor were significantly increased in samples from equol-producing women. Multivariable analysis showed that, after isoflavone treatment, the fecal microbial communities of equol producers were more like each other. Isoflavone supplementation increased the production of caproic acid, suggesting differential microbial activity, leading to a high fecal excretion of this compound. However, differences between equol producers and non-producers were not scored. These results may contribute to characterizing the modulating effect of isoflavones on the gut microbiota, which could lead to unravelling of their beneficial health effects.


Assuntos
Isoflavonas , Microbiota , Suplementos Nutricionais , Fezes , Feminino , Humanos , Pós-Menopausa , RNA Ribossômico 16S/genética
20.
Zhongguo Zhong Yao Za Zhi ; 46(14): 3650-3659, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34402289

RESUMO

Puerarin has the anti-Alzheimer's disease (AD) activity,which can reverse nerve injury induced by Aßand inhibit neuronal apoptosis.However,its potential pharmacodynamic mechanism still needs to be further researched.The occurrence and development of AD is due to the change of multiple metabolic links in the body,which leads to the destruction of balance.Puerarin may act on multiple targets and multiple metabolic processes to achieve therapeutic purposes.Quantitative proteomic analysis provides a new choice to understand the mechanism as completely as possible.This research adopted SH-SY5Y cells induced by Aß_(1-42)to establish AD cell model,and Aßimmunofluorescence detection showed that Aßdecreased significantly after puerarin intervention.The mechanism of puerarin reversing SH-SY5Y cell injured by Aß_(1-42)was further explored by using label-free non-labeled quantitative technology and Western blot detection based on bioinformatics analysis result.The results showed that most of the differential proteins were related to biological processes such as cellular component organization or biogenesis,cellular component organization and cellular component biogenesis,and they mainly participated in the top ten pathways of P value such as pathogenic Escherichia coli infection,m TOR signaling pathway,regulation of autophagy,regulation of actin cytoskeleton,spliceosome,hepatocellular carcinoma,tight junction,non-small cell lung cancer,apoptosis and gap junction.Annexin V/PI flow cytometry and TUNEL were used to detect apoptosis,and the results showed that Aßdecreased significantly and the rate of apoptosis decreased significantly after puerarin intervention.Western blot analysis found that the protein expression level of autophagy related protein LC3Ⅱwas up-regulated after Aßinduction,and the degree of this up-regulation was further enhanced in puerarin intervention group.The trend of the ratio of LC3Ⅱ/LC3Ⅰamong groups was the same as the protein expression level of LC3Ⅱ,the protein expression level of p62 in the control group,AD model group and puerarin intervention group decreased successively.Protein interaction network analysis showed that CAP1 was correlated with TUBA1B,HSP90AB2P,DNM1L,TUBA1A and ERK1/2,and the correlation between CAP1 and ERK1/2 was the highest among them.Western blot showed that the expressions of p-ERK1/2,Bax and CAP1 were significantly down-regulated and the protein expression level of Bcl-2 was significantly up-regulated after puerarin intervention.Therefore,puerarin might improve the SH-SY5Y cells injured by Aß_(1-42)through the interaction of multiple biological processes and pathways in cells multiple locations,and CAP1 might play an important role among them.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Isoflavonas , Neoplasias Pulmonares , Peptídeos beta-Amiloides , Apoptose , Linhagem Celular Tumoral , Humanos , Isoflavonas/farmacologia , Proteômica
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