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1.
AAPS PharmSciTech ; 23(1): 2, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34796406

RESUMO

Daidzein, an aglycone-type isoflavone, is useful in the prevention of atherosclerotic cardiovascular diseases. However, the solubility of daidzein remains relatively low even with pharmaceutical interventions (e.g., γ-cyclodextrin inclusion complex). In the present study, daidzein-cyclodextrin-metal organic framework solid dispersion complexes were prepared by the solvent evaporation method. The physicochemical properties of the complex and its effect on the solubility of daidzein were evaluated. The enhancement effect of a cyclodextrin-metal organic framework on the antioxidant properties of daidzein was verified using a diphenyl-picrylhydrazyl radical scavenging test. Powder X-ray diffraction results showed that the characteristic diffraction peaks of daidzein and cyclodextrin-metal organic framework disappeared and new peaks (2θ = 7.1°, 16.5°) were observed. FT-IR measurements showed that the peak derived from the carbonyl group of daidzein shifted to the lower wavenumber. NOESY 1H-1H NMR showed cross peaks at the proton on the resorcinol side of daidzein and the proton (H-5, H-6) in a cyclodextrin-metal organic framework. Dissolution rate of daidzein at 5 min in distilled water was 0.06% for daidzein alone while the daidzein inclusion complex was about 100%. When fasted state simulated intestinal fluid was used, the dissolution rate of the daidzein complex was about 71% compared with that of daidzein alone (~ 3.0%) at 5 min. The daidzein inclusion complex improved the antioxidant capacity to ~ 1.3 times (17.8 µg/mL) compared to the IC50 of daidzein alone (22.9 µg/mL). Preparations of cyclodextrin-metal organic framework inclusion complexes will be a platform in developing pharmaceutical formulations to enhance the bioavailability and activity of drugs.


Assuntos
Ciclodextrinas , Isoflavonas , Estruturas Metalorgânicas , beta-Ciclodextrinas , Antioxidantes , Varredura Diferencial de Calorimetria , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
2.
Pestic Biochem Physiol ; 179: 104963, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34802513

RESUMO

Glabridin is a natural plant-derived compound that has been widely used in medicine and cosmetic applications. However, the fungicidal mechanism of glabridin against phytopathogens remains unclear. In this study, we determined the biological activity and physiological effects of glabridin against F. graminearum. Then the differentially expressed proteins of F. graminearum were screened. The EC50 values of glabridin in inhibiting the mycelial growth and conidial germination of F. graminearum were 110.70 mg/L and 40.47 mg/L respectively. Glabridin-induced cell membrane damage was indicated by morphological observations, DiBAC4(3) and PI staining, and measurements of relative conductivity, ergosterol content and respiratory rates. These assays revealed that the integrity of the membrane was destroyed, the content of ergosterol decreased, and the respiratory rate was inhibited. A proteomics analysis showed that 186 proteins were up-regulated and 195 proteins were down-regulated. Mechanically sensitive ion channel proteins related to transmembrane transport and ergosterol biosynthesis ERG4/ERG24, related to ergosterol synthesis were blocked. It is speculated that glabridin acts on ergosterol synthesis-related proteins to destroy the integrity of the cell membrane, resulting in abnormal transmembrane transport and an increased membrane potential. Finally, the morphology of mycelia was seriously deformed, growth and development were inhibited. As a result death was even induced.


Assuntos
Fungicidas Industriais , Fusarium , Isoflavonas , Fenóis/farmacologia , Doenças das Plantas
3.
Molecules ; 26(20)2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34684855

RESUMO

Vitexin is a C-glucoside flavone that exhibits a wide range of pharmaceutical activities. However, the poor solubility of vitexin limits its applications. To resolve this limitation, two glycoside hydrolases (GHs) and four glycosyltransferases (GTs) were assayed for glycosylation activity toward vitexin. The results showed that BtGT_16345 from the Bacillus thuringiensis GA A07 strain possessed the highest glycosylation activity, catalyzing the conversion of vitexin into new compounds, vitexin-4'-O-ß-glucoside (1) and vitexin-5-O-ß-glucoside (2), which showed greater aqueous solubility than vitexin. To our knowledge, this is the first report of vitexin glycosylation. Based on the multiple bioactivities of vitexin, the two highly soluble vitexin derivatives might have high potential for pharmacological usage in the future.


Assuntos
Apigenina/metabolismo , Glucosídeos/metabolismo , Bacillus thuringiensis/metabolismo , Catálise , Flavonas/metabolismo , Glicosilação , Glicosiltransferases/metabolismo , Isoflavonas/metabolismo , Solubilidade
4.
Molecules ; 26(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34641407

RESUMO

Isoflavones are polyphenols primarily contained in soybean. As phytoestrogens, isoflavones exert beneficial effects on various chronic diseases. Metabolic syndrome increases the risk of death due to arteriosclerosis in individuals with various pathological conditions, including obesity, hypertension, hyperglycemia, and dyslipidemia. Although the health benefits of soybean-derived isoflavones are widely known, their beneficial effects on the pathogenesis of metabolic syndrome are incompletely understood. This review aims to describe the association between soybean-derived isoflavone intake and the risk of metabolic syndrome development. We reviewed studies on soy isoflavones, particularly daidzein and genistein, and metabolic syndrome, using PubMed, ScienceDirect, and Web of Science. We describe the pathological characteristics of metabolic syndrome, including those contributing to multiple pathological conditions. Furthermore, we summarize the effects of soybean-derived daidzein and genistein on metabolic syndrome reported in human epidemiological studies and experiments using in vitro and in vivo models. In particular, we emphasize the role of soy isoflavones in metabolic syndrome-induced cardiovascular diseases. In conclusion, this review focuses on the potential of soy isoflavones to prevent metabolic syndrome by influencing the onset of hypertension, hyperglycemia, dyslipidemia, and arteriosclerosis and discusses the anti-inflammatory effects of isoflavones.


Assuntos
Isoflavonas/farmacologia , Síndrome Metabólica/prevenção & controle , Alimentos de Soja/análise , Soja/química , Animais , Humanos
5.
Molecules ; 26(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34641584

RESUMO

Despite its classification as a non-life-threatening disease, increased skin pigmentation adversely affects quality of life and leads to loss of self-confidence. Until now, there are no recommended remedies with high efficacy and human safety for hyperpigmentation. This study aimed to investigate anti-melanogenic activity and underlying mechanism of cajanin, an isoflavonoid extracted from Dalbergia parviflora Roxb. (Leguminosae) in human melanin-producing cells. Culture with 50 µM cajanin for 48-72 h significantly suppressed proliferation in human melanoma MNT1 cells assessed via MTT viability assay. Interestingly, cajanin also efficiently diminished melanin content in MNT1 cells with the half maximum inhibitory concentration (IC50) at 77.47 ± 9.28 µM. Instead of direct inactivating enzymatic function of human tyrosinase, down-regulated mRNA and protein expression levels of MITF and downstream melanogenic enzymes, including tyrosinase, TRP-1 and Dct (TRP-2) were observed in MNT1 cells treated with 50 µM cajanin for 24-72 h. Correspondingly, treatment with cajanin modulated the signaling pathway of CREB and ERK which both regulate MITF expression level. Targeted suppression on MITF-related proteins in human melanin-producing cells strengthens the potential development of cajanin as an effective treatment for human hyperpigmented disorders.


Assuntos
Isoflavonas/farmacologia , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Fator de Transcrição Associado à Microftalmia/efeitos dos fármacos , Fator de Transcrição Associado à Microftalmia/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Dalbergia/química , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Hiperpigmentação/tratamento farmacológico , Interferon Tipo I/metabolismo , Oxirredutases Intramoleculares/metabolismo , Isoflavonas/química , Melaninas/biossíntese , Melanócitos/efeitos dos fármacos , Melanócitos/enzimologia , Melanócitos/metabolismo , Melanoma/enzimologia , Monofenol Mono-Oxigenase/metabolismo , Extratos Vegetais/farmacologia , Proteínas da Gravidez/metabolismo , Qualidade de Vida
6.
Ecotoxicol Environ Saf ; 227: 112886, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34673406

RESUMO

Atrazine (ATR) is a widely used herbicide that can induce the degeneration of dopaminergic (DAergic) neurons in the substantia nigra, resulting in a Parkinson's disease-like syndrome. Despite the high risk of environmental exposure, few studies have investigated strategies for the prevention of ATR neurotoxicity. Our previous studies demonstrated that ATR can impair mitochondrial function, leading to metabolic failure. Cells maintain mitochondrial quality through selective autophagic elimination, termed mitophagy. Soybean isoflavones (SI) possess multiple beneficial bioactivities, including preservation of mitochondria function, so it was hypothesized that SI can protect neurons against ATR toxicity by promoting mitophagy. Pretreatment of SH-SY5Y neurons with SI prevented ATR-induced metabolic failure and cytotoxicity as assessed by intracellular ATP, Na+-K+-ATPase activity, mitochondrial membrane potential, and cell viability assays. The neuroprotective efficacy of SI was superior to the major individual components genistein, daidzein, and glycitein. Ultrastructural analyses revealed that ATR induced mitochondrial damage, while SI promoted the sequestration of damaged mitochondria into autophagic vesicles. Soybean isoflavones also induced mitophagy as evidenced by upregulated expression of BNIP3/NIX, BEX2, and LC3-II, while co-treatment with the mitophagy inhibitor Mdivi-1 blocked SI-mediated neuroprotection and prevented SI from reversing ATR-induced BEX2 downregulation. Furthermore, BEX2 knockdown inhibited SI-induced activation of the BNIP3/NIX pathway, mitophagy, and neuroprotection. These findings suggest that SI protects against ATR-induced mitochondrial dysfunction and neurotoxicity by activating the BEX2/BNIP3/NIX pathway.


Assuntos
Atrazina , Isoflavonas , Atrazina/toxicidade , Neurônios Dopaminérgicos , Isoflavonas/farmacologia , Proteínas de Membrana , Mitofagia , Soja
7.
Artigo em Inglês | MEDLINE | ID: mdl-34639339

RESUMO

This study investigated the binding abilities of extracellular polymers produced by an environmentally isolated strain of Enterococcus hirae towards phytoestrogen endocrine disruptors-biochanin A, formonetin, genistein and daidzein. The extracellular biopolymer exhibited notable binding and removal for all four phytoestrogens, with a maximum removal of daidzein (87%) followed by genistein (72%) at a 1-1.5 mg/mL concentration. Adsorption proceeded rapidly at ambient temperature. The adsorption data fitted well with the Langmuir isotherm. Based on the adsorption energy, the biopolymer binding of phytoestrogens was inferred as daidzein > genistein > biochanin A > formononetin. Toxicity of the biopolymer (5-250 µg/mL) evaluated using RAW 264.7 cell lines indicated no significant (p < 0.05) changes in viability. In biopolymer-challenged Caenorhabditis elegans previously exposed to daidzein, complete protection to developmental toxicity, such as reduced egg-laying capacity, egg viability and progeny counts of the worm, was observed. The results of this study offer valuable insights into understanding the potential role of microbial extracellular biopolymers in binding and removal of phytoestrogens with sustainable technological implications in modulating the toxic effect of high levels of endocrine disruptors in the environment.


Assuntos
Disruptores Endócrinos , Isoflavonas , Animais , Caenorhabditis elegans , Disruptores Endócrinos/toxicidade , Genisteína/toxicidade , Fitoestrógenos/toxicidade , Polímeros , Água
8.
Chem Biol Interact ; 349: 109681, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34600870

RESUMO

Irigenin, an isoflavonoid isolated from the rhizome of Belamcanda chinensis, possess various pharmacological effects. However, the effect and mechanism of irigenin on intervertebral disc degeneration (IDD) remain unclear. The potential targets of irigenin or disease were predicted using PharmMapper or GeneCards databases, respectively. The overlapping targets were inputted into the String database to establish protein-protein interaction (PPI) network. The overlapping targets were also submitted to DAVID webserver to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Nucleus pulposus (NP) cells were exposed to 10 ng/mL tumor necrosis factor-α (TNF-α) to establish a cell model of IDD. Cell viability, LDH content, apoptosis and caspase-3 activity were evaluated by CCK-8, LDH release, TUNEL, and caspase-3 activity assays, respectively. The expression of collagen II, aggrecan, matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, and MMP-13 were detected by qRT-PCR and western blot analyses. The network analysis revealed that MMP-2, MMP-3, MMP-9, MMP-13, caspase-3 (CASP3), vitamin D receptor (VDR), insulin-like growth factor 1 (IGF1), and transforming growth factor beta2 (TGFB2) play key roles in the effect of irigenin against IDD. TNF-α stimulation inhibited cell viability and increased LDH content, apoptosis, caspase-3 expression and caspase-3 activity in NP cells, which were reversed by irigenin treatment. TNF-α stimulation inhibited the expression of collagen II and aggrecan and upregulated MMPs (MMP-2, MMP-3, MMP-9, and MMP-13) in NP cells, while such changes were abolished by irigenin treatment. In conclusion, irigenin suppressed apoptosis and ECM degradation in TNF-α-stimulated NP cells by reducing the expression of caspase-3 and MMPs.


Assuntos
Caspase 3/metabolismo , Matriz Extracelular/metabolismo , Isoflavonas/fisiologia , Metaloproteinases da Matriz/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Células Cultivadas , Humanos
9.
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
10.
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
11.
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
12.
Phytother Res ; 35(10): 5838-5846, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34494323

RESUMO

The aim of this study was to examine the effect of whole soy and purified daidzein on markers of thyroid function in Chinese postmenopausal women who were equol-producers. Total 270 eligible women were randomized to either one of the three isocaloric supplements: 40 g soy flour (whole soy group), 40 g low-fat milk powder +63 mg daidzein (daidzein group) or 40 g low-fat milk powder (placebo) daily for 6 months. Serum thyroid markers were tested at baseline and 6 months for thyroid stimulating hormone, free triiodothyronine, reverse triiodothyronine and free thyroxine (FT4). There was no significant difference in the 6-month changes of thyroid markers among the three groups. Subgroup analysis among women with lowered thyroid function suggested a modest decrease of FT4. This randomized controlled trial among Chinese equol-producing postmenopausal women indicates the consumption of whole soy and purified daidzein at the provided dosages are safe and have no detrimental effect on thyroid function.


Assuntos
Equol , Isoflavonas , China , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Pós-Menopausa , Glândula Tireoide
13.
Molecules ; 26(17)2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34500814

RESUMO

The investigation of the constituents of the rhizomes of Dioscorea collettii afforded one new dihydroisocoumarin, named (-)-montroumarin (1a), along with five known compounds-montroumarin (1b), 1,1'-oxybis(2,4-di-tert-butylbenzene) (2), (3R)-3'-O-methylviolanone (3a), (3S)-3'-O-methylviolanone (3b), and (RS)-sativanone (4). Their structures were elucidated using extensive spectroscopic methods. To the best of our knowledge, compound 1a is a new enantiomer of compound 1b. The NMR data of compound 2 had been reported but its structure was erroneous. The structure of compound 2 was revised on the basis of a reinterpretation of its NMR data (1D and 2D) and the assignment of the 1H and 13C NMR data was given rightly for the first time. Compounds 3a-4, three dihydroisoflavones, were reported from the Dioscoreaceae family for the first time. The cytotoxic activities of all the compounds were tested against the NCI-H460 cell line. Two dihydroisocoumarins, compounds 1a and 1b, displayed moderate cytotoxic activities, while the other compounds showed no cytotoxicity.


Assuntos
Cumarínicos/química , Dioscorea/química , Isoflavonas/química , Rizoma/química , Derivados de Benzeno/química , Linhagem Celular Tumoral , Cumarínicos/toxicidade , Humanos , Isoflavonas/toxicidade , Extratos Vegetais/química
14.
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
15.
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
16.
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
17.
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
18.
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
19.
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
20.
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
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