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1.
Phytochemistry ; 179: 112496, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33070076

RESUMO

Elicited soybean (Glycine max (L.) Merrill, Leguminosae) seedlings can produce prenylated isoflavonoids from different subclasses, namely pterocarpans (glyceollins), isoflavones and coumestans. These prenylated isoflavonoids serve as defence compounds and can possess antimicrobial activity. Recently, we showed that priming with reactive oxygen species (ROS) specifically stimulated the production of glyceollins in Rhizopus spp.-elicited soybean seedlings (ROS + R). In this study, we achieved diversification of the inducible subclasses of prenylated isoflavonoids in soybean, by additional stimulation of two prenylated isoflavones and one prenylated coumestan. This was achieved by using a combination of the relatively long-lived ROS representative, H2O2, with AgNO3 prior to microbial elicitation. Microbial elicitation was performed with a live preparation of either a phytopathogenic fungus, Rhizopus spp. or a symbiotic bacterium, Bacillus subtilis. B. subtilis induced 30% more prenylated isoflavones than Rhizopus spp. in (H2O2 + AgNO3)-treated seedlings, without significantly compromising the total levels of glyceollins, compared to (ROS + R)-treated seedlings. The most abundant prenylated isoflavone induced was 6-prenyl daidzein, which constituted 60% of the total isoflavones. The prenylated coumestan, phaseol, was also induced in the (H2O2 + AgNO3)-treated and microbially elicited seedlings. Based on previously developed quantitative structure-activity relationship (QSAR) models, 6-prenyl daidzein and phaseol were predicted to be promising antibacterials. Overall, we show that treatment with H2O2 and AgNO3 prior to microbial elicitation leads to the production of promising antibacterial isoflavonoids from different subclasses. Extracts rich in prenylated isoflavonoids may potentially be applied as natural antimicrobial agents.


Assuntos
Fabaceae , Isoflavonas , Antibacterianos/farmacologia , Peróxido de Hidrogênio , Isoflavonas/farmacologia , Plântula , Soja
2.
PLoS One ; 15(8): e0237929, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822403

RESUMO

BACKGROUND: Neuroinflammation causes neurodegenerative conditions like Alzheimer's disease (AD). Ipriflavone (IP), therapeutic compound to postmenopausal osteoporosis, has limited estrogenic activity and is accounted as AChE inhibitor. The developing of drug delivery systems to enable drug targeting to specific sites increases the drug therapeutic effect. OBJECTIVE: The aim of the present study was to formulate and evaluate ipriflavone loaded albumin nanoparticles (IP-Np) along with free ipriflavone against lipopolysaccharide (LPS) induced neuroinflammation in rats. METHODS: Neuroinflammation was induced by intra-peritoneal (i.p) injection of LPS (250 µg/kg rat body weight) then treatments were conducted with (1) ipriflavone at two doses 50 mg/kg and 5 mg/kg, (2) IP-Np (5 mg ipriflavone/kg) or (3) IP-Np coated with polysorbate 80 (IP-Np-T80) (5 mg ipriflavone/kg). The alteration of the inflammatory response in male adult Wistar rats' brain hippocampus was investigated by examining associated indices using biochemical and molecular analyses. RESULTS: A significant upsurge in inflammatory mediators and decline in antioxidant status were observed in LPS-induced rats. In one hand, ipriflavone (50 mg/kg), IP-Np and IP-Np-T80 ameliorated LPS induced brain hippocampal inflammation where they depreciated the level of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) and enhanced antioxidant status. In another hand, ipriflavone at dose (5 mg/kg) didn't show the same therapeutic effect. CONCLUSION: The current study provides evidence for the potential neuroprotective effect of ipriflavone (50 mg/kg) against LPS-induced neuroinflammation in rats through its anti-inflammatory and antioxidant activities. Moreover, nanoparticles significantly attenuated neuroinflammation in concentration lower than the effective therapeutic dose of free drug ten times.


Assuntos
Hipocampo/efeitos dos fármacos , Inflamação/tratamento farmacológico , Isoflavonas/uso terapêutico , Nanopartículas , Fármacos Neuroprotetores/uso terapêutico , Acetilcolinesterase/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Inibidores da Colinesterase/farmacologia , Citocinas/metabolismo , Sistemas de Liberação de Medicamentos , Hipocampo/enzimologia , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Inflamação/metabolismo , Inflamação/fisiopatologia , Isoflavonas/administração & dosagem , Isoflavonas/farmacologia , Lipopolissacarídeos/toxicidade , Masculino , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Nanopartículas/ultraestrutura , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Soroalbumina Bovina/química , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
3.
Chem Biol Interact ; 329: 109213, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32739323

RESUMO

Phytoestrogens are plant-derived substances with a similar structure to 17-beta-estradiol, which have protective roles in estrogen-dependent diseases. Isoflavones, the most well-known subgroup of phytoestrogens, play protective roles against chemicals-induced liver injuries through several molecular mechanisms. Hepatoprotective effects of isoflavones are, partly, associated with their antioxidant, anti-inflammatory, immunomodulatory, and anti-fibrotic properties. Besides, isoflavones can reduce gut-derived endotoxins, accelerate alcohol metabolism, stimulate detoxification of hepatotoxic chemicals, suppress the bioactivation of these chemicals, inhibit hepatocytes apoptosis, and restore autophagy activity during chemicals-induced liver diseases. This review provides a summary of the molecular mechanisms underlying the hepatoprotective effects of isoflavones. It seems that further studies are needed to investigate the hepatoprotective potential of isoflavones in patients with different stages of chemicals-induced liver injuries.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Isoflavonas/metabolismo , Substâncias Protetoras/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Inflamação/prevenção & controle , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Cirrose Hepática/metabolismo , Cirrose Hepática/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia
4.
J Pharmacol Exp Ther ; 374(2): 308-318, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32546528

RESUMO

ME-344 is a second-generation cytotoxic isoflavone with anticancer activity promulgated through interference with mitochondrial functions. Using a click chemistry version of the drug together with affinity-enriched mass spectrometry, voltage-dependent anion channels (VDACs) 1 and 2 were identified as drug targets. To determine the importance of VDAC1 or 2 to cytotoxicity, we used lung cancer cells that were either sensitive (H460) or intrinsically resistant (H596) to the drug. In H460 cells, depletion of VDAC1 and VDAC2 by small interfering RNA impacted ME-344 effects by diminishing generation of reactive oxygen species (ROS), preventing mitochondrial membrane potential dissipation, and moderating ME-344-induced cytotoxicity and mitochondrial-mediated apoptosis. Mechanistically, VDAC1 and VDAC2 knockdown prevented ME-344-induced apoptosis by inhibiting Bax mitochondrial translocation and cytochrome c release as well as apoptosis in these H460 cells. We conclude that VDAC1 and 2, as mediators of the response to oxidative stress, have roles in modulating ROS generation, Bax translocation, and cytochrome c release during mitochondrial-mediated apoptosis caused by ME-344. SIGNIFICANCE STATEMENT: Dissecting preclinical drug mechanisms are of significance in development of a drug toward eventual Food and Drug Administration approval.


Assuntos
Antineoplásicos/farmacologia , Isoflavonas/farmacologia , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Canal de Ânion 2 Dependente de Voltagem/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Isoflavonas/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2/metabolismo
5.
An Acad Bras Cienc ; 92 Suppl 1: e20181371, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32491139

RESUMO

The formononetin biostimulant may be an option for reducing P fertilization once it stimulates mycelial growth of arbuscular mycorrhizal fungi and increases plant ability to take up nutrients through the roots, especially phosphorus. The objective of this study was to evaluate the effect of formononetin associated with phosphorus fertilization in maize. Field experiments were conducted in a randomized block design with a 3 × 4 factorial arrangement (0, 50 or 70, and 140 kg ha-1 P2O5; and formononetin application rates: 0, 25, 50, and 100 g ha-1), with four replications. Formononetin (100 g ha-1) increased the mycorrhizal colonization rate up to 30% in maize in the first four weeks after emergence when no P fertilizer was applied, and to 17% when 50 or 70 kg ha-1 of P2O5 were applied. The application of 50 and 100 g ha-1 of formononetin significantly increased plant height, ear height, and grain yield (22% - 76%) when no P fertilizer was applied. The use of formononetin in the field stimulates mycorrhizal colonization, has a positive effect on maize yield, and reduces the need for P fertilizer application in maize. However, this effect was evident only at low P soil contents.


Assuntos
Fertilizantes , Isoflavonas/farmacologia , Fósforo/análise , Solo/química , Zea mays/crescimento & desenvolvimento , Micorrizas/fisiologia , Zea mays/efeitos dos fármacos
6.
Life Sci ; 256: 117935, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32526286

RESUMO

AIMS: Retinal ischemia/reperfusion (I/R) injury is common in the development of ophthalmic diseases and potentially causes blindness. In present study, the aim is to investigate the possible protective effects of puerarin on retinal I/R. MAIN METHODS: Retinal I/R injury was conducted on the left eyes of male Sprague Dawley rats, which were subsequently received treatment with puerarin. After administration, retinal I/R-induced apoptosis, oxidative stress and inflammatory responses were detected. Meanwhile, we purified retinal ganglion cells (RGCs) from 7-day-old rats. After subjected RGCs to oxygen and glucose deprivation/reoxygenation (OGD/R), apoptosis and TLR4/NLRP3 inflammasome activation in RGCs were detected. KEY FINDINGS: Puerarin prominently suppressed apoptosis, alleviated oxidative stress and suppressed TLR4/NLRP3 inflammasome activation in rats with retinal I/R injury. Consistent with our in vivo study, we found puerarin ameliorated retinal I/R injury through suppressing apoptosis and TLR4/NLRP3 inflammasome activation in RGCs. SIGNIFICANCE: Our findings reveal that puerarin plays a protective role against retinal I/R injury by alleviating RGC damage, and is beneficial for the treatment of I/R injury-caused ophthalmic diseases.


Assuntos
Isoflavonas/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Doenças Retinianas/tratamento farmacológico , Células Ganglionares da Retina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Humanos , Inflamassomos/metabolismo , Masculino , Modelos Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Retina/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo
7.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(3): 242-247, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32389172

RESUMO

Objective To investigate the mechanism of formononetin regulating the heat production of brown adipocytes via decoupling protein 1 (UCP1). Methods The brown preadipocytes was isolated from wild-type (WT) C57BL/6J mice and differentiated into mature fat cells in vitro. Moreover, the mRNA levels of fatty acid binding protein 4 (FABP4) and adiponectin were detected by real-time quantitative PCR (RT-qPCR). To confirm formononetin could induce the expression of thermogenic genes, we first prepared WT mature brown adipocytes and treated them with DMSO and formononetin separately. The mRNA and protein levels of thermogenic genes, such as peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), peroxisome proliferators-activated receptor γ (PPARγ), UCP1 and iodothyronine deiodinase 2 (Dio2), were detected by RT-qPCR and Western blot analysis. To investigate the role of UCP1 in mediating differentiation of brown preadipocytes, Fabp4 and adiponectin mRNA levels were analyzed by RT-qPCR in WT and UCP1 mutation differentiated brown adipocytes. To determine cellular oxygen consumption, isolated WT and UCP1 mutation brown preadipocytes were plated in an XF24-well microplate and differentiated into mature brown adipocytes treated with formononetin or DMSO, followed by oxygen consumption rate (OCR) measurement using XF24 analyser. Results Both WT and UCP1 KO brown preadipocytes could be differentiated into adipocyte. The expression of thermogenic genes, including PGC-1α, Dio2, PPARγ and UCP1, induced by formononetin was similar in UCP1 KO adipocytes and WT cells. But the ability of formononetin to increase cellular respiration was inhibited in Ucp1 KO cells. Conclusion Formononetin mediated stimulation of thermogenesis and oxygen consumption via UCP1 in brown fat cells.


Assuntos
Adipócitos Marrons/efeitos dos fármacos , Isoflavonas/farmacologia , Termogênese , Proteína Desacopladora 1/fisiologia , Adipócitos Marrons/metabolismo , Animais , Diferenciação Celular , Células Cultivadas , Técnicas de Inativação de Genes , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais , Fatores de Transcrição , Proteína Desacopladora 1/genética
8.
Rev Assoc Med Bras (1992) ; 66(2): 174-179, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32428152

RESUMO

OBJECTIVE: Although estrogen therapy is widely used against post-menopausal symptoms, it can present adverse effects, including endometrial cancer. Soy isoflavones are considered a possible alternative to estrogen therapy. However, there are still concerns whether isoflavones exert trophic effects on the uterine cervix. To evaluate the histomorphometric and immunohistochemical alterations in the uterine cervix of ovariectomized rats treated with soy isoflavones (Iso). METHODS: Fifteen adult Wistar rats were ovariectomized (Ovx) and divided into three groups: Group I (Ovx), administered with vehicle solution; Group II (OVX-Iso), administered with concentrated extract of Iso (150 mg/kg) by gavage; and Group III (OVX-E2), treated with 17ß-estradiol (10 µg/kg), subcutaneously. After 30 days of treatments, the uterine cervix was fixed in 10% formaldehyde and processed for paraffin-embedding. Sections were stained with Hematoxylin and eosin for morphological and morphometric studies or subjected to immunohistochemistry for detections of Ki-67 and vascular endothelial growth factor-A (Vegf-A). The data obtained were subjected to statistical analysis (p ≤ 0.05). RESULTS: We noted an atrophic uterine cervix in GI, whereas it was more voluminous in GII and even more voluminous in GIII. The thickness of the cervical mucosa was significantly higher in GIII, as compared to GI and GII. The cell proliferation (Ki-67) was significantly elevated in the estradiol and isoflavones treated groups, whereas Vegf-A immunoexpression was significantly higher in GIII, as compared to groups GII and GI. CONCLUSIONS: Soy isoflavones cause less trophic and proliferative effects in the uterine cervix of rats as compared to estrogen.


Assuntos
Colo do Útero/efeitos dos fármacos , Estrogênios/farmacologia , Isoflavonas/farmacologia , Fitoestrógenos/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Colo do Útero/patologia , Epitélio/efeitos dos fármacos , Feminino , Imuno-Histoquímica , Antígeno Ki-67/análise , Membrana Mucosa/efeitos dos fármacos , Ovariectomia , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/análise
9.
J Anim Sci ; 98(6)2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32379891

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important disease, and the ingestion of soy isoflavones (ISF) may benefit PRRSV-infected pigs due to demonstrated anti-inflammatory and antiviral properties. The objective of this study was to quantify the effects of ISF consumption on fecal microbiome characteristics at different timepoints across a disease challenge and determine whether any changes, if present, elude to potential biological mechanisms for previously observed performance benefits. In total, 96 weaned barrows were group-housed in a Biosafety Level-2 containment facility and allotted to one of three experimental treatments that were maintained throughout the study: noninfected pigs receiving an ISF-devoid control diet (NEG, n = 24) and infected pigs receiving either the control diet (POS, n = 36) or that supplemented with total ISF in excess of 1,600 mg/kg (ISF, n = 36). Following a 7-d adaptation, pigs were inoculated intranasally with either a sham-control (phosphate-buffered saline) or live PRRSV (1 × 105 median tissue culture infectious dose[TCID]50/mL, strain NADC20). Fecal samples were collected from 48 individual pigs at pre-infection (-2 d post-inoculation [DPI]), peak-infection (10 DPI), and post-infection (144 DPI) timepoints. Extracted DNA was used to quantify fecal microbiota profiles via 16S bacterial rRNA sequencing. Differences in bacterial communities among diet groups were evaluated with principal coordinate analysis and permutational multivariate analysis of variance using UniFrac distance matrices based on both unweighted and weighted UniFrac distances using QIIME 2. All other data were analyzed by one-way ANOVA performed on square root transformations using R. Across all timepoints, only a few differences were observed due to ISF alone mainly in lowly abundant genera. The most notable differences observed were decreased relative abundance of Actinobacteria at 144 DPI between noninfected and infected treatments (P < 0.05), which is consistent with various dysbioses observed in other disease models. Our findings indicate that the differences present were mainly due to PRRSV-infection alone and not strongly influenced by diet, which implies that previously observed performance benefits conferred by dietary ISF are not likely due to the changes in microbiome composition.


Assuntos
Isoflavonas/farmacologia , Microbiota/efeitos dos fármacos , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína , Soja/química , Doenças dos Suínos/virologia , Ração Animal/análise , Animais , Dieta , Suplementos Nutricionais/análise , Ingestão de Alimentos/efeitos dos fármacos , Fezes/microbiologia , Masculino , Síndrome Respiratória e Reprodutiva Suína/microbiologia , Suínos , Doenças dos Suínos/microbiologia
10.
Braz J Med Biol Res ; 53(4): e8882, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294699

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common primary malignant tumors of the liver worldwide. Liver resection and transplantation are currently the only effective treatments; however, recurrence and metastasis rates are still high. Previous studies have shown that the epithelial-mesenchymal transition (EMT) is a key step in HCC invasion and metastasis. Inhibition of EMT has become a new therapeutic strategy for tumors. Recently, puerarin, a well-characterized component of traditional Chinese medicine, has been isolated from Pueraria radix and exerts positive effects on many diseases, particularly cancers. In this study, CCK-8, EdU immunofluorescence, colony formation, wound healing, and migration assays were used to detect the effects of puerarin on HCC cells. We further analyzed the relationship between puerarin and miR-21/PTEN/EMT markers in HCC cell lines. Our results showed that HCC cell proliferation, migration, invasion, tumor formation, and metastasis were reduced by puerarin in vitro and in vivo. Additionally, puerarin inhibited the EMT process of HCC by affecting the expression of Slug and Snail. Moreover, oncogenic miR-21 was inhibited by puerarin, coupled with an increase in the tumor suppressor gene PTEN. Increasing miR-21 expression or decreasing PTEN expression reversed the inhibition effects of puerarin in HCC. These data confirmed that puerarin affects HCC through the miR-21/PTEN/EMT regulatory axis. Overall, puerarin may represent a chemopreventive and/or chemotherapeutic agent for HCC treatment.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Isoflavonas/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , PTEN Fosfo-Hidrolase/genética , Animais , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Modelos Animais de Doenças , Ensaios de Seleção de Medicamentos Antitumorais , Isoflavonas/farmacologia , Neoplasias Hepáticas/genética , Masculino , MicroRNAs/genética , Invasividade Neoplásica , Pirróis
11.
Biochem Biophys Res Commun ; 525(3): 759-766, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32145915

RESUMO

Formononetin (FN), a methoxy isoflavone abundant in many plants and herbs, has been evidently proven to possess multiple medicinal properties. Our study aimed to clarify the impact of FN on myocardial ischemia/reperfusion (I/R) injury (MIRI) and the involved mechanism. A rat model of MIRI was produced by ligation and loosening of the left anterior descending (LAD) branch of the coronary artery. Rats received 10 and 30 mg/kg of FN when the reperfusion started. At 24 h after surgery, cardiac function, infarct size, and sera levels of the cardiac markers and inflammatory mediators were measured. To mimic the inflammasome activation in cardiomyocytes, neonatal rat cardiomyocytes (NRCMs) were cultured and treated with lipopolysaccharide (LPS) plus nigericin. Cell death and reactive oxygen species (ROS) were determined. Myocardial expression and activation of the nucleotide-binding domain and leucine-rich repeat-containing protein 3 (NLRP3) inflammasome in rats were examined by western blotting. The level of thioredoxin interacting protein (TXNIP)-NLRP3 interaction was assessed. FN notably attenuated cardiac dysfunction, infarct size, release of cardiac markers, and elevation of TNF-α, IL-1ß, and IL-6. FN alleviated LPS plus nigericin-induced injury and ROS increase in NRCMs. Western blotting revealed that FN suppressed the activation of NLRP3 inflammasome and TXNIP-NLRP3 interaction in rats. These findings indicate that FN ameliorated MIRI in rats and inhibited the activation of the NLRP3 inflammasome, at least partially, attributable to suppression of the ROS-TXNIP-NLRP3 pathway.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Isoflavonas/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Testes de Função Cardíaca , Inflamassomos/metabolismo , Inflamação/patologia , Isoflavonas/química , Isoflavonas/farmacologia , Lipopolissacarídeos , Masculino , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Nigericina , Ligação Proteica/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
12.
Braz J Med Biol Res ; 53(3): e9201, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130294

RESUMO

Methylophiopogonanone A (MO-A), a homoisoflavonoid extracted from Ophiopogon japonicus, has been shown to attenuate myocardial apoptosis and improve cerebral ischemia/reperfusion injury. However, the hypolipidemic effects remain unknown. This study was performed to investigate a potential hypolipidemic effect of MO-A in hyperlipidemia rats, as well as its underlying mechanism of action. A rat model of hyperlipidemia was induced by a high-fat diet (HFD). Animals were randomly divided into three groups (n=8/group): normal control group (NC), HFD group, and HFD+MO-A (10 mg·kg-1·d-1) treatment group. The effects of MO-A on serum lipids, body weight, activity of lipoprotein metabolism enzyme, and gene expression of lipid metabolism were evaluated in HFD-induced rats. In HFD-induced rats, pretreatment with MO-A decreased the body weight gain and reduced serum and hepatic lipid levels. In addition, pretreatment with MO-A improved the activities of lipoprotein lipase and hepatic lipase in serum and liver, down-regulated mRNA expression of acetyl CoA carboxylase and sterol regulatory element-binding protein 1c, and up-regulated mRNA expression of low-density lipoprotein receptor and peroxisome proliferator-activated receptor α in the liver. Our results indicated that MO-A showed strong ability to ameliorate the hyperlipidemia in HFD-induced rats. MO-A might be a potential candidate for prevention of overweight and dyslipidemia induced by HFD.


Assuntos
Benzodioxóis/farmacologia , Dieta Hiperlipídica , Hiperlipidemias/prevenção & controle , Isoflavonas/farmacologia , Metabolismo dos Lipídeos , Ophiopogon/química , Animais , Benzodioxóis/isolamento & purificação , Western Blotting , Modelos Animais de Doenças , Fezes/química , Hiperlipidemias/metabolismo , Isoflavonas/isolamento & purificação , Lipídeos/análise , Masculino , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real
13.
PLoS One ; 15(3): e0229200, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32168321

RESUMO

Biochanin A, an isoflavone present in the pasture legume red clover (Trifloium pratense L.), alters fermentation in the rumen of cattle and other ruminants. Biochanin A inhibits hyper-ammonia-producing bacteria and promotes cellulolytic bacteria and fiber catalysis in vitro and ex vivo. Consequently, biochanin A supplementation improves weight gain in grazing steers. Red clover contains biologically active isoflavones that may act synergistically. Therefore, the objective was to evaluate the effect of two levels of red clover hay on growth performance and the microbial community in growing steers grazing mixed grass pastures. A grazing experiment was conducted over 2 early growing seasons (2016 and 2017) with 36 cross-bred steers and twelve rumen-fistulated, growing Holstein steers for evaluation of average daily gain and rumen microbiota, respectively. Steers were blocked by body weight and assigned to pastures with one of four treatments: 1) pasture only, 2) pasture + dry distillers' grains (DDG), 3) pasture + DDG + low level of red clover hay (~15% red clover diet), or 4) pasture + DDG + high level of red clover hay (~30% red clover diet). DDG were added to treatments to meet protein requirements and to balance total protein supplementation between treatments. All supplementation strategies (DDG ± red clover hay) increased average daily gains in comparison to pasture-only controls (P < 0.05), with a low level of red clover supplementation being the most effective (+0.17 kg d-1 > DDG only controls; P < 0.05). Similarly, hyper-ammonia-producing bacteria inhibition (10-100-fold; P < 0.05), fiber catalysis (+10-25%; P < 0.05) and short chain fatty acid concentrations were greatest with the low red clover supplement (+~25%; P < 0.05). These results provide evidence that lower levels or red clover supplementation may be optimal for maximizing overall microbial community function and animal performance in grazing steers.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Isoflavonas/administração & dosagem , Rúmen/microbiologia , Trifolium/química , Ganho de Peso , Ração Animal/análise , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Catálise , Bovinos , Relação Dose-Resposta a Droga , Hibridização Genética , Isoflavonas/farmacologia , Fibras Nervosas Mielinizadas/química , Extratos Vegetais/química , Rúmen/efeitos dos fármacos
14.
J Appl Microbiol ; 129(3): 532-540, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32160376

RESUMO

AIM: To examine the synergistic effect of calycosin combined with polymyxin B against various mcr-1-positive bacterial strains. METHODS AND RESULTS: In this study, we found a potential inhibitor of MCR-1, calycosin, that could significantly restore the antibacterial activity of polymyxin B. The synergistic effect of calycosin combined with polymyxin B against various mcr-1-positive bacterial strains was confirmed by checkerboard minimum inhibitory concentration assays, time-kill curve assays and disk diffusion assays. The fractional inhibitory concentration indexes ranged from 0·15 ± 0·03 to 0·28 ± 0·05, and the zones of inhibition increased from 13·33 ± 0·47 to 17·67 ± 0·47 mm with the combined therapy of calycosin and polymyxin B. In addition, the combined therapy significantly reduced the number of bacteria in the medium. However, at the concentrations required for the synergistic effect with polymyxin B, calycosin alone showed no effect on bacterial growth or MCR-1 production. Calycosin treatment exhibited no cytotoxicity to HeLa cells or A549 cells at calycosin concentrations below 32 µg ml-1 . CONCLUSIONS: Therefore, our results suggested that calycosin could be used as a potential MCR-1 inhibitor to restore the bactericidal effect of polymyxin B without affecting bacterial viability or existing cytotoxicity. SIGNIFICANCE AND IMPACT OF THE STUDY: The synergistic effect of calycosin combined with polymyxin B against various mcr-1-positive bacterial strains paves the way for future pharmaceutical applications of calycosin in fighting mcr-1-positive bacterial infections.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Isoflavonas/farmacologia , Polimixina B/farmacologia , Células A549 , Sinergismo Farmacológico , Células HeLa , Humanos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos
15.
J Anim Sci ; 98(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32166330

RESUMO

The objective was to evaluate the effects of porcine reproductive and respiratory syndrome virus (PRRSV) infection and dietary soy isoflavone (ISF) supplementation on carcass cutability and meat quality of commercial pigs. Barrows (21 d of age) were randomly allotted to experimental treatments that were maintained throughout the study: noninfected pigs received an ISF-devoid control diet (CON, n = 22) and infected pigs received either the control diet (PRRSV-CON, n = 20) or that supplemented with total ISF in excess of 1,500 mg/kg (PRRSV-ISF, n = 25). Pigs were penned by treatment, with six pigs within a pen. Following a 7-d adaptation, weanling pigs were inoculated once intranasally with either a sham-control (phosphate buffered saline [PBS]) or live PRRSV (1 × 105 tissue culture infective dose [TCID]50/mL, strain NADC20). Pigs were maintained on experimental diets for 166 d after inoculation and then slaughtered (192 or 194 d of age; approximately 120 kg body weight [BW]). At 1-d postmortem, left sides were separated between the 10th and 11th rib for the determination of loin eye area (LEA), backfat (BF) thickness, and loin quality (ultimate pH, instrumental color, drip loss, visual color, marbling, and firmness). Loin chops were aged 14 d postmortem prior to Warner-Bratzler shear force (WBSF) determination. Belly width, length, thickness, and flop distance were determined. Data were analyzed as a one-way ANOVA with pig as the experimental unit. Carcass yield, LEA, BF, and estimated lean percentage did not differ (P > 0.26) among treatments. Loins from CON pigs had increased ultimate pH (P = 0.01), reduced L* scores (P = 0.005) coupled with darker visual color scores (P = 0.004), were firmer (P < 0.0001), and exhibited reduced drip loss (P = 0.01) compared with PRRSV-CON and PRRSV-ISF pigs. However, WBSF did not differ (P = 0.51) among treatments after 14 d of aging. Bellies from CON pigs were more firm compared with bellies from PRRSV-CON and ISF pigs (P < 0.01). These data suggest PRRSV infection did not alter carcass characteristics but may have marginally reduced loin and belly quality. Supplementation with dietary soy isoflavones did nothing to mitigate the detrimental effects of PRRSV infection.


Assuntos
Composição Corporal/efeitos dos fármacos , Dieta/veterinária , Suplementos Nutricionais , Isoflavonas/farmacologia , Síndrome Respiratória e Reprodutiva Suína/patologia , Carne de Porco/normas , Ração Animal/análise , Animais , Peso Corporal , Masculino , Vírus da Síndrome Respiratória e Reprodutiva Suína , Suínos
16.
J Food Sci ; 85(4): 1302-1306, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32144772

RESUMO

The effects and mechanisms of soybean isoflavone on osteoblast (OB) proliferation in vitro were investigated. Fifty female Wistar rats were randomly divided into five groups with 10 rats in each group. Rat OBs were separated and cultured. The first generation of OBs cultured for 48 hr at various concentrations of isoflavone were set as the experimental groups, the OBs exposed to estradiol (E2 ) culture were considered as positive control group. The biological characterization of OBs was investigated by phase contrast microscopy and alkaline phosphatase (ALP) histochemistry. The concentrations of interleukin (IL-1), osteoprotegerin (OPG), transforming growth factor (TGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) in isoflavone culture solutions were determined. Proliferation rate of OBs was increased in experimental group comparing that in the blank group. ALP activity in experimental group was higher than that in blank group. No significant differences of ALP activity were observed between E2 culture group and isoflavone group at concentrations of 10-5 and 10-7 mM (P > 0.05). Furthermore, in the experimental groups at low isoflavone concentrations, the concentrations of OPG, TGF, and VEGF were increased and positively correlated with OB proliferation. However, the concentrations of IL-1, GM-CSF were decreased at higher concentration of isoflavone and were negatively correlated with OB proliferation. Soybean isoflavone could promote the growth and proliferation of rat OB, it might act as the stimulator of OPG, TGF, and VEGF pathway, and the inhibitor of IL-1, GM-CSF pathway as well.


Assuntos
Isoflavonas/farmacologia , Osteoblastos/efeitos dos fármacos , Soja/química , Fosfatase Alcalina , Animais , Células Cultivadas , Citocinas/metabolismo , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Isoflavonas/química , Osteoblastos/metabolismo , Ratos , Ratos Wistar , Soja/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Curr Med Sci ; 40(1): 123-129, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32166674

RESUMO

Albiziae Flos (AF) has been experimentally proven to have an antidepressant effect. However, due to the complexity of botanical ingredients, the exact pharmacological mechanism of action of AF in depression has not been completely deciphered. This study used the network pharmacology method to construct a component-target-pathway network to explore the active components and potential mechanisms of action of AF. The methods included collection and screening of chemical components, prediction of depression-associated targets of the active components, gene enrichment, and network construction and analysis. Quercetin and 4 other active components were found to exert antidepressant effects mainly via monoaminergic neurotransmitters and cAMP signaling and neuroactive ligand-receptor interaction pathways. DRD2, HTR1A, and SLC6A4 were identified as important targets of the studied bioactive components of AF. This network pharmacology analysis provides guidance for further study of the antidepressant mechanism of AF.


Assuntos
Albizzia/química , Antidepressivos/farmacologia , Redes Reguladoras de Genes/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Antidepressivos/química , Humanos , Isoflavonas/química , Isoflavonas/farmacologia , Quempferóis/química , Quempferóis/farmacologia , Luteolina/química , Luteolina/farmacologia , Compostos Fitoquímicos/química , Extratos Vegetais/química , Quercetina/análogos & derivados , Quercetina/química , Quercetina/farmacologia , Receptor 5-HT1A de Serotonina/metabolismo , Receptores de Dopamina D2/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Transdução de Sinais/efeitos dos fármacos
18.
Phytomedicine ; 68: 153171, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32018211

RESUMO

BACKGROUND: Cardiac hypertrophy is a prominent feature of heart remodeling, which may eventually lead to heart failure. Tongmaiyangxin (TMYX) pills are a clinically used botanical drug for treating multiple cardiovascular diseases including chronic heart failure. The aim of the current study was to identify the bioactive compounds in Tongmaiyangxin pills that attenuate cardiomyocytes hypertrophy, and to investigate the underlying mechanism of action. METHODS AND RESULTS: The anti-hypertrophy effect of TMYX was validated in isoproterenol-induced cardiac hypertrophy model in C57BL/6 mice. After TMYX treatment for 2 weeks, the heart ejection fraction and fractional shortening of the mice model was increased by approximately 20% and 15%, respectively, (p < 0.05). Besides, TMYX dose-dependently reduced the cross section area of cardiomyocytes in the angiotensin-II induced hypertrophy H9c2 model (p < 0.01). Combining high content screening and liquid chromatography mass spectrometry, four compounds with anti-cardiac hypertrophy effects were identified from TMYX, which includes emodin, licoisoflavone A, licoricone and glyasperin A. Licoisoflavone A is one of the compounds with most significant protective effect and we continued to investigate the mechanism. Primary cultures of neonatal rat cardiomyocytes were treated with a hypertrophic agonist phenylephrine (PE) in the presence or absence of licoisoflavone A. After 48 h of treatment, cells were harvested and mitochondrial acetylation was analyzed by western blotting and Image analysis. Interestingly, the results suggested that the anti-hypertrophic effects of licoisoflavone A depend on the activation of the deacetylase Sirt3 (p < 0.01). Finally, we showed that licoisoflavone A-treatment was able to decrease relative ANF and BNP levels in the hypertrophic cardiac cells (p < 0.01), but not in cells co-treated with Sirt3 inhibitors (3-TYP) (p > 0.05). CONCLUSION: TMYX exerts its anti-hypertrophy effect possibly through upregulating Sirt3 expression. Four compounds were identified from TMYX which may be responsible for the anti-hypertrophy effect. Among these compounds, licoisoflavone A was demonstrated to block the hypertrophic response of cardiomyocytes, which required its positive regulation on the expression of Sirt3. These results suggested that licoisoflavone A is a potential Sirt3 activator with therapeutic effect on cardiac hypertrophy.


Assuntos
Cardiomegalia/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Isoflavonas/farmacologia , Sirtuína 3/metabolismo , Acetilação , Angiotensina II/efeitos adversos , Animais , Cardiomegalia/induzido quimicamente , Células Cultivadas , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Isoproterenol/efeitos adversos , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fenilefrina/efeitos adversos , Ratos
19.
Phytomedicine ; 68: 153177, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32106002

RESUMO

BACKGROUND: Calycosin is a bioactive isoflavonoid of the medicinal plant Astragalus membranaceus that exhibits a wide range of pharmacological properties. In the present study, we have attempted to explore the anti-tumorigenic potential of calycosin in pancreatic cancer. METHODS: MTT assay was used to determine cancer cell viability. Cell cycle analysis and detection of apoptosis were performed using flow cytometry. A wound healing assay was employed to study the migratory activity of cancer cells. Western blotting and RT-PCR were used to explore the mechanism by assessing the target proteins and genes. An orthotopic tumor xenograft mouse model was also used to study the drug effects in vivo. RESULTS: Calycosin inhibited the growth of pancreatic cancer cells by inducing p21Waf1/Cip1-induced cell cycle arrest and caspase-dependent apoptosis. Alternatively, it also promoted MIA PaCa-2 cell migration by eliciting epithelial-mesenchymal transition (EMT) and matrix metalloproteinase activation. In vivo study has confirmed that calycosin would provoke the pro-invasive and angiogenic drive and subsequent EMT in pancreatic tumors. Further mechanistic study suggests that induction of the Raf/MEK/ERK pathway and facilitated polarization of M2 tumor-associated macrophage in the tumor microenvironment both contribute to the pro-metastatic potential of calycosin. These events appear to be associated with increased expression of TGF-ß1 at both transcriptional and post-translational levels, which may explain the paradoxical drug actions since TGF-ß has been implicated to play dual roles as both tumor suppressor and tumor promoter in pancreatic cancer development. CONCLUSION: Findings of this study provide innovative insights about the impact of calycosin in pancreatic cancer progression through induction of cell cycle arrest and apoptosis while possessing certain tumor-promoting property by modulation of the tumor microenvironment.


Assuntos
Isoflavonas/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Fator de Crescimento Transformador beta/metabolismo , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Isoflavonas/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Pancreáticas/metabolismo , Células RAW 264.7 , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Fitoterapia ; 141: 104479, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31927011

RESUMO

BACKGROUND: Homoisoflavonoids have been shown to have potent anti-proliferative activities in endothelial cells over other cell types and have demonstrated a strong antiangiogenic potential in vitro and in vivo in animal models of ocular neovascularization. Three species of Rhodocodon (Scilloideaea subfamily of the Asparagaceae family), endemic to Madagascar, R. cryptopodus, R. rotundus and R. cyathiformis, were investigated. PURPOSE: To isolate and test homoisoflavonoids for their antiangiogenic activity against human retinal microvascular endothelial cells (HRECs), as well as specificity against other ocular cell lines. METHODS: Plant material was extracted at room temperature with EtOH. Compounds were isolated using flash column chromatography and were identified using NMR and CD spectroscopy and HRESIMS. Compounds were tested for antiproliferative effects on primary human microvascular retinal endothelial cells (HRECs), ARPE19 retinal pigment epithelial cells, 92-1 uveal melanoma cells, and Y79 retinoblastoma cells. HRECs exposed to compounds were also tested for migration and tube formation ability. RESULTS: Two homoisoflavonoids, 3S-5,7-dihydroxy-(3'-hydroxy-4'-methoxybenzyl)-4-chromanone (1) and 3S-5,7-dihydroxy-(4'-hydroxy-3'-methoxybenzyl)-4-chromanone (2), were isolated along with four bufadienolides. Compound 1 was found to be non-specifically antiproliferative, with GI50 values ranging from 0.21-0.85 µM across the four cell types, while compound 2 showed at least 100-fold specificity for HRECs over the other tested cell lines. Compound 1, with a 3S configuration, was 700 times more potent that the corresponding 3R enantiomer recently isolated from a Massonia species. CONCLUSION: Select homoisoflavonoids have promise as antiangiogenic agents that are not generally cytotoxic.


Assuntos
Asparagaceae/química , Bufanolídeos/química , Isoflavonas/química , Isoflavonas/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Humanos , Vasos Retinianos/citologia
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