Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.876
Filtrar
1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
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
8.
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
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.
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
11.
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
12.
Complement Ther Med ; 61: 102764, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34333131

RESUMO

BACKGROUND: Soy protein in combination with soy isoflavones might reduce the serum concentration of inflammatory mediators. In this study, we attempted to summarize the effect of soy protein combined with soy isoflavones on circulating E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in adults. METHODS: Clinicaltrials.gov, Web of Science, Cochrane Library, PubMed, and Scopus were searched for English articles with no time limit regarding publication up to December 2020. Thereafter, the mean changes from baseline and their standard deviations (SDs) for both intervention and comparison groups were used to calculate the effect size. We used DerSimonian and Laird random-effects model if the heterogeneity test was statistically significant. Cochran's Q test and I-squared statistic were also used to calculate the statistical heterogeneity of the intervention effects. RESULTS: Eight articles were found as eligible for this study. The treatment duration was between 6 and 24 weeks. Soy isoflavones dose was in a range of 30-112 mg/day and soy protein dose was in a range of 11.25-52 g/day. Overall, taking soy protein supplements containing soy isoflavones was not associated with changes in cell adhesion molecules, E-selectin, ICAM-1, or VCAM-1 (WMD = 0.65, 95 % CI: -2.58, 3.89; p = 0.692; WMD = 2.68, 95 % CI: -0.98, 6.34; p = 0.151; WMD = 2.66, 95 % CI: -6.28, 11.61; p = 0.559, respectively). CONCLUSION: The combination of soy protein and soy isoflavones was not significantly associated with changes in levels of E-selectin, ICAM-1, and VCAM-1. However, we need more studies with a large sample size and more participants with different age categories in this regard.


Assuntos
Isoflavonas , Proteínas de Soja , Moléculas de Adesão Celular , Humanos , Isoflavonas/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas de Soja/farmacologia
13.
Int J Mol Sci ; 22(14)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34299247

RESUMO

A series of new heteroleptic copper(II) complexes of the composition [Cu(L)(bpy)]NO3·2MeOH (1), [Cu(L)(dimebpy)]NO3·2H2O (2), [Cu(L)(phen)]NO3·2MeOH (3), [Cu(L)(bphen)]NO3·MeOH (4), [Cu(L)(dppz)]NO3·MeOH (5) was prepared, where HL = 3-(3,4-dihydroxyphenyl)-5-hydroxy-8,8-dimethyl-6-(3-methylbut-2-ene-1-yl)-4H,8H-benzo[1,2-b:3,4-b']dipyran-4-one, (pomiferin) and bpy = 2,2'-bipyridine, dimebpy = 4,4'-dimethyl-2,2'-bipyridine, phen = 1,10-phenanthroline, bphen = 4,7-diphenyl-1,10-phenanthroline, and dppz = dipyrido[3,2-a:2',3'-c]phenazine. The complexes were characterized using elemental analysis, infrared and UV/Vis spectroscopies, mass spectrometry, thermal analysis and conductivity measurements. The in vitro cytotoxicity, screened against eight human cancer cell lines (breast adenocarcinoma (MCF-7), osteosarcoma (HOS), lung adenocarcinoma (A549), prostate adenocarcinoma (PC-3), ovarian carcinoma (A2780), cisplatin-resistant ovarian carcinoma (A2780R), colorectal adenocarcinoma (Caco-2) and monocytic leukemia (THP-1), revealed the complexes as effective antiproliferative agents, with the IC50 values of 2.2-13.0 µM for the best performing complexes 3 and 5. All the complexes 1-5 showed the best activity against the A2780R cells (IC50 = 2.2-6.6 µM), and moreover, the complexes demonstrated relatively low toxicity on healthy human hepatocytes, with IC50 > 100 µM. The complexes were evaluated by the Annexin V/propidium iodide apoptosis assay, induction of cell cycle modifications in A2780 cells, production of reactive oxygen species (ROS), perturbation of mitochondrial membrane potential, inhibition of apoptosis and inflammation-related signaling pathways (NF-κB/AP-1 activity, NF-κB translocation, TNF-α secretion), and tested for nuclease mimicking activity. The obtained results revealed the corresponding complexes to be effective antiproliferative and anti-inflammatory agents.


Assuntos
Benzopiranos/farmacologia , Complexos de Coordenação/farmacologia , Cobre/química , Isoflavonas/farmacologia , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Benzopiranos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/química , Cobre/metabolismo , Cobre/farmacologia , Flavonoides/metabolismo , Flavonoides/farmacologia , Humanos , Isoflavonas/química , Espécies Reativas de Oxigênio/metabolismo
14.
Chem Biol Interact ; 348: 109569, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34197824

RESUMO

As one of the most important members of Phthalate esters (PAEs), di-(2-ethylhexyl) phthalate (DEHP) is widely used in plastics and known as a male reproductive toxicant. Many studies have shown that soybean isoflavones (SI) can rescue the testicular injury caused by DEHP, but the underlying mechanism is unknown. Because methylation is one of the most important mechanisms for maintaining normal biological functions, we studied whether methylation is involved in testicular injury induced by DEHP and whether SI could counter testicular impairment in peripubertal male Sprague Dawley rats. Compared with the control group, we found that the mRNA levels of testicular Sod2, Gpx1, and Igf-1 significantly decreased in the 900 mg/kg DEHP group (DEHP' group) (P < 0.01); however, in the DEHP + SI group, the mRNA levels of the genes obviously increased compared with the DEHP' group (P < 0.01). Simultaneously, the methylation level changes of testicular Sod2, Gpx1, and Igf-1 were similar to the mRNA levels (P < 0.01). Therefore, DEHP may affect testis and leydig cells via inducing methylation of Sod2, Gpx1, and Igf-1, and SI may rescue the impairments at the methylation level. In summary, SI is supposed to be used in DEHP-induced testicular injury treatment.


Assuntos
Metilação de DNA/efeitos dos fármacos , Dietilexilftalato/toxicidade , Isoflavonas/farmacologia , Soja/química , Testículo/efeitos dos fármacos , Testículo/lesões , Animais , Citoproteção/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Células Intersticiais do Testículo/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Reprodução/efeitos dos fármacos , Testículo/citologia , Testículo/metabolismo
15.
Molecules ; 26(14)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34299411

RESUMO

Clitorea ternatea has been used in Ayurvedic medicine as a brain stimulant to treat mental illnesses and mental functional disorders. In this study, the metabolite profiles of crude C. ternatea root extract (CTRE), ethyl acetate (EA), and 50% aqueous methanol (50% MeOH) fractions were investigated using ultrahigh-performance liquid chromatography-diode array detector-tandem mass spectrometry (UHPLC-DAD-MS/MS), while their effect on the stress-like behavior of zebrafish, pharmacologically induced with reserpine, was investigated. A total of 32 compounds were putatively identified, among which, a series of norneolignans, clitorienolactones, and various flavonoids (flavone, flavonol, isoflavone, and isoflavanone) was found to comprise the major constituents, particularly in the EA and 50% MeOH fractions. The clitorienolactones, presently unique to the species, were present in both the free and glycosylated forms in the roots. Both the EA and 50% MeOH fractions displayed moderate effects on the stress-induced zebrafish model, significantly decreasing freezing duration and elevating the total distance travelled and average velocity, 72 h post-treatment. The results of the present study provide further evidence that the basis for the use of C. ternatea roots in traditional medicine to alleviate brain-related conditions, such as stress and depression, is attributable to the presence of clitorienolactones and the isoflavonoidal constituents.


Assuntos
Clitoria/química , Depressão/tratamento farmacológico , Flavonoides/farmacologia , Lactonas/farmacologia , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Estresse Fisiológico/efeitos dos fármacos , Animais , Comportamento Animal , Depressão/induzido quimicamente , Isoflavonas/farmacologia , Reserpina/toxicidade , Peixe-Zebra
16.
Sci Rep ; 11(1): 14180, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244528

RESUMO

High resistance towards traditional antibiotics has urged the development of new, natural therapeutics against methicillin-resistant Staphylococcus aureus (MRSA). Prenylated (iso)flavonoids, present mainly in the Fabaceae, can serve as promising candidates. Herein, the anti-MRSA properties of 23 prenylated (iso)flavonoids were assessed in-vitro. The di-prenylated (iso)flavonoids, glabrol (flavanone) and 6,8-diprenyl genistein (isoflavone), together with the mono-prenylated, 4'-O-methyl glabridin (isoflavan), were the most active anti-MRSA compounds (Minimum Inhibitory Concentrations (MIC) ≤ 10 µg/mL, 30 µM). The in-house activity data was complemented with literature data to yield an extended, curated dataset of 67 molecules for the development of robust in-silico prediction models. A QSAR model having a good fit (R2adj 0.61), low average prediction errors and a good predictive power (Q2) for the training (4% and Q2LOO 0.57, respectively) and the test set (5% and Q2test 0.75, respectively) was obtained. Furthermore, the model predicted well the activity of an external validation set (on average 5% prediction errors), as well as the level of activity (low, moderate, high) of prenylated (iso)flavonoids against other Gram-positive bacteria. For the first time, the importance of formal charge, besides hydrophobic volume and hydrogen-bonding, in the anti-MRSA activity was highlighted, thereby suggesting potentially different modes of action of the different prenylated (iso)flavonoids.


Assuntos
Antibacterianos/farmacologia , Flavonoides/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Antibacterianos/química , Flavonoides/química , Humanos , Isoflavonas/química , Isoflavonas/farmacologia , Fenóis/química , Fenóis/farmacologia , Prenilação , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia
17.
J Nanobiotechnology ; 19(1): 197, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34217311

RESUMO

Intra-articular (IA) injection is an efficient treatment for osteoarthritis, which will minimize systemic side effects. However, the joint experiences rapid clearance of therapeutics after intra-articular injection. Delivering system modified through active targeting strategies to facilitate localization within specific joint tissues such as cartilage is hopeful to increase the therapeutic effects. In this study, we designed a nanoscaled amphiphilic and cartilage-targeting polymer-drug delivery system by using formononetin (FMN)-poly(ethylene glycol) (PEG) (denoted as PCFMN), which was prepared by PEGylation of FMN followed by coupling with cartilage-targeting peptide (CollBP). Our results showed that PCFMN was approximately regular spherical with an average diameter about 218 nm. The in vitro test using IL-1ß stimulated chondrocytes indicated that PCFMN was biocompatible and upregulated anabolic genes while simultaneously downregulated catabolic genes of the articular cartilage. The therapeutic effects in vivo indicated that PCFMN could effectively attenuate the progression of OA as evidenced by immunohistochemical staining and histological analysis. In addition, PCFMN showed higher intention time in joints and better anti-inflammatory effects than FMN, indicating the efficacy of cartilage targeting nanodrug on OA. This study may provide a reference for clinical OA therapy.


Assuntos
Isoflavonas/química , Isoflavonas/farmacologia , Osteoartrite/tratamento farmacológico , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Animais , Anti-Inflamatórios , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Interleucina-1beta/metabolismo , Masculino , Nanopartículas , Osteoartrite/metabolismo , Osteoartrite/patologia , Peptídeos , Ratos Sprague-Dawley
18.
Biomed Pharmacother ; 140: 111448, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34130202

RESUMO

Isoflavones are a group of secondary metabolites found in plants belonging to the class of phytoestrogens. These, because they have a chemical structure similar to the endogenous hormone 17ß-estradiol, act as endocrine disruptors over the different development window periods. This study aimed to evaluate male and female reproductive systems' responses when exposed to isoflavones during the development window. It is characterized as a bibliographic review, built after analyzing clinical and preclinical articles indexed in English, Portuguese, and Spanish published in the last ten years. The isoflavones, aglycone or glucosides, have essential therapeutic properties in the relief of postmenopausal symptoms in women, reduce the proliferation of cancers, in addition to being antioxidants. On the other hand, they can still behave in a similar way to 17ß-estradiol, binding to hormone receptors and acting as endocrine disruptors over the gestational period until pre-puberty, negatively affecting the development of the reproductive system. The effects on reproduction are not dose-response but are influenced by the type of isoflavone and period. There are variations in the serum concentration of hormones and action on their negative feedback on the hypothalamic-pituitary-testicular axis in males. Reproductive functions are also affected by spermatogenesis, such as decreased sperm count, lower reproductive performance, reduced litter size, low sperm production, and reduced seminal vesicle size. In females, puberty is reached later, irregular estrous cycle, reduced weight of the ovary, uterus, lower serum levels of estradiol and progesterone, reduced fertility, or interrupted fertility. At the end of the analysis of the selected publications, it can be concluded that despite the beneficial therapeutic effects in the face of pathologies, the unknown consumption of doses and types of isoflavones in food can damage the development and reproduction of individuals. Therefore, further studies must be carried out to elucidate the usual safe doses of the analyzed phytoestrogen. Greater control over insertion in foods targeted at pediatric consumers should be implemented until we have adequate safety.


Assuntos
Fertilidade/efeitos dos fármacos , Isoflavonas/farmacologia , Animais , Feminino , Hormônios/sangue , Humanos , Masculino , Fitoestrógenos/farmacologia , Reprodução/efeitos dos fármacos
19.
Aging (Albany NY) ; 13(12): 16009-16023, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34096887

RESUMO

In this study, we investigated the effects of calycosin on breast cancer cell progression and their underlying mechanisms. Calycosin dose- and time-dependently inhibited proliferation, migration, and invasion by T47D and MCF-7 breast cancer cells by downregulating basic leucine zipper ATF-like transcription factor (BATF) expression. Moreover, BATF promoted breast cancer cell migration and invasiveness by increasing TGFß1 mRNA and protein levels. Bioinformatics analysis, dual luciferase reporter assays, and chromatin immunoprecipitation assays confirmed the presence of BATF-binding sites in the promoter sequence of TGFß1 gene. Calycosin treatment inhibited epithelial-mesenchymal transition (EMT) of breast cancer cells by significantly increasing E-cadherin levels and decreasing N-cadherin, Vimentin, CD147, MMP-2, and MMP-9 levels through downregulation of BATF and TGFß1. TGFß1 knockdown reduced the migration and invasiveness of BATF-overexpressing breast cancer cells, whereas incubation with TGFß1 enhanced the migration and invasiveness of calycosin-treated breast cancer cells. Our findings demonstrated that calycosin inhibited EMT and progression of breast cancer cells by suppressing BATF/TGFß1 signaling. This suggests calycosin would be a promising therapeutic option for breast cancer patients.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Neoplasias da Mama/patologia , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Isoflavonas/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Sequência de Bases , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Regulação para Baixo/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Invasividade Neoplásica , Metástase Neoplásica
20.
Fitoterapia ; 153: 104977, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34157375

RESUMO

The genus Poiretia belongs to the Fabaceae (Leguminosae) family and it encompasses twelve species of flowering plants. The chemistry of this genus is scarcely investigated, although some studies have demonstrated the potential of Poiretia species to produce important bioactive compounds. Herein, we describe the phytochemical investigation of P. bahiana C. Mueller leaves. A new isoflavone glucoside named as 2',4',5'-trimethoxyisoflavone-7-O-ß-D-glucopyranoside (1), along with six known isoflavones (2-7), two rotenones (8-9), cyclitol 3-O-methyl-chiro-inositol (10), the amino acid proline (11), a mixture of sitosterol (12) and stigmasterol (13), and a mixture of the triterpenes lupeol (14) and ß-amirine (15) were obtained from P. bahiana leaves. The structures were established by extensive analysis of their spectroscopic data, which included 1H NMR, 13C NMR, DEPT, and 2D-NMR (13C1H HETCOR and 13C1H COLOC). Two isoflavones (3 and 5) and two rotenones (8-9) exhibited antifungal activity against the plant pathogenic fungus Cladosporium sphaerospermum. Furthermore, the biogenetic implications of the oxygenation pattern of the B-ring of the isoflavones, and the chemophenetics and fragmentation pattern of the isoflavones and rotenones are discussed.


Assuntos
Fabaceae/química , Fungicidas Industriais/farmacologia , Glucosídeos/farmacologia , Isoflavonas/farmacologia , Brasil , Cladosporium/efeitos dos fármacos , Fungicidas Industriais/isolamento & purificação , Glucosídeos/isolamento & purificação , Isoflavonas/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...