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1.
Oncol Rep ; 47(1)2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34738632

RESUMO

Colon cancer is one of the most commonly diagnosed malignancies, which begins as a polyp and grows to become cancer. Diosmin (DS) and naringenin (NR) are naturally occurring flavonoids that exhibit various pharmacological activities. Although several studies have illustrated the effectiveness of these flavonoids as anti­cancerous agents individually, the combinatorial impact of these compounds has not been explored. In the present study, the combined effect of DS and NR (DiNar) in colon cancer cell lines HCT116 and SW480 were assessed by targeting apoptosis and inflammatory pathways. The MTT assay was used to evaluate the effect of DiNar on cell proliferation, while Chou­Talalay analysis was employed to determine the combination index of DS and NR. Moreover, flow cytometry was used to monitor cell cycle arrest and population study. The onset of apoptosis was assessed by DAPI staining, DNA fragmentation, and Annexin V­fluorescein isothiocyanate/propidium iodide (Annexin V­FITC/PI). The expression levels of apoptotic pathway markers, Bcl­2, Bax, caspase3, caspase8, caspase9 and p53, and inflammatory markers, NF­κß, IKK­α and IKK­ß, were assessed using western blotting and reverse transcription­quantitative PCR. These results suggested that DiNar treatment acts synergistically and induces cytotoxicity with a concomitant increase in chromatin condensation, DNA fragmentation and cell cycle arrest in the G0/G1 phase. Annexin V­FITC/PI apoptosis assay also showed increased number of cells undergoing apoptosis in the DiNar treatment group. Furthermore, the expression of apoptosis and inflammatory markers was also more effectively regulated under the DiNar treatment. Thereby, these findings demonstrated that DiNar treatment could be a potential novel chemotherapeutic alternative in colon cancer.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Diosmina/farmacologia , Flavanonas/farmacologia , Antineoplásicos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Células HCT116 , Humanos
2.
Toxicol Mech Methods ; 32(1): 58-66, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34348583

RESUMO

Human exposure to nanoparticles became unavoidable secondary to their massive involvement in a multitude of industrial applications. Zinc oxide nanoparticles (ZnONPs) are one of the most commonly used metal oxide nanoparticles in biological applications. Naringenin (NAR), a citrus-derived flavonoid, has favorable biological properties that promote human health. The present study was carried out to investigate the possible defensive role of NAR versus ZnONPs provoked hepatic injury in rats through an evaluation of liver enzymes, hepatic biomarkers of oxidative stress, inflammatory process, apoptotic cell death along with histopathological examination of liver tissue. Therefore, 32 adult rats were randomly divided into four equal groups as control, NAR, ZnONPs and co-treated ZnONPs with NAR groups. All treatments were administered for 14 days. Our results showed that ZnONPs induced hepatic injury as documented by the marked increased in hepatic enzymes activities, disturbed hepatic oxidant/antioxidant balance, increased hepatic inflammatory reactions, in addition to, extensive hepatic morphological alterations, marked collagen fibers accumulation as well as overexpression of apoptotic BAX and the noticeable intensified positive nuclear staining for nuclear factor Kabba-b in hepatic tissues. Concurrent NAR supplement to ZnONPs- treated rats significantly declined liver enzymes activities, restored oxidant/antioxidant balance, reversed inflammation, induced fewer collagen fibers accumulation, and antagonized BAX-mediated apoptotic cell death in hepatic tissues. We concluded that concurrent NAR supplement to ZnONPs treated rats improved hepatic function and structure by its antioxidant, anti-inflammatory and antiapoptotic potentials.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Óxido de Zinco , Animais , Antioxidantes , Apoptose , Flavanonas , Fígado , Nanopartículas Metálicas/toxicidade , Nanopartículas/toxicidade , Estresse Oxidativo , Ratos , Óxido de Zinco/toxicidade
3.
Food Chem ; 371: 131065, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34560336

RESUMO

Citrus fruits are a good source of flavanones. The present study aimed to assess the effect of food matrix elements [dietary fibres (DFs)] on the flavanone profile of grapefruit peel (GFP) and on the gut microbiota during in vitro digestion and simulated colonic fermentation. The contents of low-molecular-weight metabolites (dihydrocaffeic acid and 3-phenylpropionic acid) were increased by pectin, konjac and chitosan in medium- and high-viscosity matrices. Compared with the GFP group, the counts of Lactobacillus spp. and Clostridium leptum were significantly increased in medium-viscosity food matrices (konjac and chitosan) (p < 0.05). Moreover, the acetic and propionic acid contents were significantly elevated in the GFP + DF groups after 12 h of fermentation (p < 0.05). GFP flavanones were retained by DF, and the total phenolic content (TPC) and antioxidant potency composite (APC) index decreased during in vitro digestion. These findings indicate that medium-viscosity DFs (konjac and chitosan) could act as key food matrix elements for the retention of polyphenols.


Assuntos
Citrus paradisi , Flavanonas , Microbiota , Fibras na Dieta/análise , Digestão , Fezes/química , Fermentação
4.
Food Chem ; 369: 130950, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34474288

RESUMO

Naringenin, a lipophilic flavanone of citrus fruits, was encapsulated for enhanced bioavailability using biodegradable polymers of polylactic acid/polyvinyl alcohol (PLA/PVA) as well as zein/pectin as P/P-Nar-NPs and Z/P-Nar-NPs, respectively. The formulation variables were optimized using response surface methodology to achieve smaller particle size with higher surface charge and encapsulation efficiencies. The optimized formulations were physically characterized by SEM, FTIR, TGA and XRD techniques. Compared to Z/P-Nar-NPs, the P/P-Nar-NPs had better encapsulation efficiency and sustained release of naringenin under simulated gastrointestinal conditions. Furthermore, the oral administration of single dose of free and nanoforms of naringenin in rats (90 mg/kg b.wt) showed higher efficacy of PLA/PVA in improving the relative bioavailability of naringenin (4.7-fold) as compared to the zein/pectin polymer (1.9-fold). Overall, the present study provides insights into the formulation performance of the encapsulated bioactive compound under different polymeric matrices.


Assuntos
Flavanonas , Nanopartículas , Zeína , Animais , Disponibilidade Biológica , Portadores de Fármacos , Tamanho da Partícula , Pectinas , Poliésteres , Álcool de Polivinil , Ratos
5.
Nutrients ; 13(12)2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34960014

RESUMO

Mounting evidence has shown that single-targeted therapy might be inadequate to achieve satisfactory effects. Thus, drug combinations are gaining attention as they can regulate multiple targets to obtain more beneficial effects. Heat shock protein 90 (HSP90) is a molecular chaperone that assists the protein assembly and folding of client proteins and maintains their stability. Interfering with the interaction between HSP90 and its client proteins by inhibiting the latter's activity may offer a new approach toward combination therapy. The HSP90 client protein AKT plays an important role in the inflammatory response syndrome caused by infections. In this study, the dietary flavone baicalein was identified as a novel inhibitor of HSP90 that targeted the N-terminal ATP binding pocket of HSP90 and hindered the chaperone cycle, resulting in AKT degradation. Combining baicalein with genipin, which was extracted from Gardenia jasminoides, could inhibit the pleckstrin homology domain of AKT, significantly increasing the anti-inflammatory effects both in vitro and in vivo. This synergistic effect was attributed to the reduction in AKT expression and phosphorylation. Thus, elucidating the mechanism underlying this effect will provide a new avenue for the clinical application and development of synergistic anti-inflammatory drugs.


Assuntos
Flavanonas/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Iridoides/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Infecções por Pseudomonas/tratamento farmacológico , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Colagogos e Coleréticos/administração & dosagem , Colagogos e Coleréticos/farmacologia , Dieta , Sistemas de Liberação de Medicamentos , Quimioterapia Combinada , Flavanonas/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Iridoides/administração & dosagem , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Pseudomonas aeruginosa , Células RAW 264.7 , Distribuição Aleatória
6.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(12): 1085-1091, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34906296

RESUMO

Objective To investigate the inhibitory effect of naringin (NAR) on proliferation and apoptosis of Eca109 esophageal cancer cells and its mechanism. Methods Eca109 cells were cultured with 0, 15, 30, 45 µmol/L NAR treatment for 24, 48 and 72 hours. The colony forming ability of Eca109 esophageal cancer cells was evaluated by cell colony forming assay, the cell proliferation activity was detected by MTT assay, and the invasion ability of cancer cells was detect by TranswellTM assay; Apoptosis was detected by annexin V-FITC/PI double labeling combined with flow cytometry. Western blot analysis was used to detect the protein expression of B-cell lymphoma factor 2 (Bcl2), Bcl2 related X protein (BAX), cytochrome C (CytC), caspase-3, caspase-9, Janus kinase 2 (JAK2), phosphorylated JAK2 (p-JAK2) and signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3 (p-STAT3), protein kinase B (AKT), phosphorylated AKT(p-AKT). Results NAR inhibited the proliferation and colony formation of Eca109 cells, suppressed the invasion of Eca109 cells and promoted the apoptosis of Eca109 cells; NAR promoted the expression of BAX, CytC, caspase-3, caspase-9, p-STAT3, p-AKT, AKT and p-JAK2 and inhibited the expression of Bcl2. Conclusion NAR can inhibit the proliferation, invasion, and colony formation of Eca109 cells and promote its apoptosis by blocking the activation of JAK/STAT signal pathway.


Assuntos
Neoplasias Esofágicas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/tratamento farmacológico , Flavanonas , Humanos , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais
7.
Biomed Eng Online ; 20(1): 125, 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34906140

RESUMO

BACKGROUND: Wogonin (5, 7-dihydroxy-8-methoxyflavone) is a natural di-hydroxyl flavonoid extracted from the root of Scutellaria baicalensis Georgi. This paper was intended to investigate the mechanism of action of wogonin in alleviating the inflammation and apoptosis in acute lung injury (ALI). MATERIALS AND METHODS: Lipopolysaccharide (LPS) was used to establish the in vitro model of ALI. After wogonin treatment, the cell viability and apoptosis of LPS-induced A549 cells were, respectively, measured by CCK-8, TUNEL assays and acridine orange/ethidium bromide dual staining, while the contents of inflammatory cytokines and oxidative stress markers were estimated by RT-qPCR, ELISA assay, western blot analysis and commercial kits. Western blot was also conducted to assess the expression of proteins involved. Subsequently, the effect of wogonin on the sirtuin 1 (SIRT1)-mediated high-mobility group box 1 protein (HMGB1) deacetylation was investigated. SIRT1 inhibitor EX527 was used to evaluate the regulatory effects of wogonin on SIRT1-mediated HMGB1 deacetylation in A549 cells under LPS stimulation. RESULTS: LPS induced inflammation, oxidative stress and apoptosis of A549 cells, which was abolished by wogonin. It was also found that wogonin promoted the HMGB1 deacetylation, accompanied by upregulated SIRT1 expression. However, SIRT1 inhibitor EX527 partially reversed the protective effects of wogonin on the inflammation and apoptosis of LPS-induced A549 cells. CONCLUSION: Wogonin alleviated the inflammation and apoptosis in LPS-induced A549 cells by SIRT1-mediated HMGB1 deacetylation, which might represent the identification of a novel mechanism by which wogonin exerts protective effects on ALI and provide ideas for the application of wogonin to ALI treatment.


Assuntos
Inflamação , Lipopolissacarídeos , Apoptose , Células Epiteliais , Flavanonas , Humanos , Lipopolissacarídeos/toxicidade , Pulmão
8.
Eur Rev Med Pharmacol Sci ; 25(21): 6741-6744, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34787879

RESUMO

OBJECTIVE: Coronaviruses are large, enveloped, positive-stranded RNA viruses. These viruses contain spike-like projections of glycoprotein on their surface, which appear like a crown. Millions of infections and thousands of deaths have been reported worldwide to date. Hence, the objective of the present study was to look for in silico evaluation of certain commercially available flavonoids against SARS-CoV-2 enzyme. MATERIALS AND METHODS: The in silico docking calculations were carried out using AutoDock 4.2 software. For the computational investigation, Apigenin, Catechin, Galangin, Luteolin, Naringenin were selected. An anti-viral drug Remdesivir was selected as reference drug. RESULTS: In the present study we found that Naringenin showed excellent binding score with the SARS-CoV-2 enzyme compared to the reference drug and other selected flavonoids. CONCLUSIONS: Based on the docking results, we conclude that Naringenin can be considered worthwhile to check its antiviral activity for the management of Coronavirus disease.


Assuntos
Antivirais/química , Simulação de Acoplamento Molecular , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Antivirais/metabolismo , Sítios de Ligação , COVID-19/patologia , COVID-19/virologia , Catequina/química , Catequina/metabolismo , Flavanonas/química , Flavanonas/metabolismo , Flavonoides/química , Flavonoides/metabolismo , Humanos , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/metabolismo
9.
Trials ; 22(1): 801, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34774104

RESUMO

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of chronic liver disease worldwide. Flavonoids, a group of natural compounds, have garnered a great deal of attention in the management of NAFLD because of their profitable effects on glucose and lipid metabolism, inflammation, and oxidative stress which are the pivotal pathophysiological pathways in NAFLD. Naringenin is a citrus-derived flavonoid with a broad spectrum of potential biological effects including anti-inflammatory and antioxidant properties, which may exert protective effects against NAFLD. The present clinical trial aims to examine the efficacy of naringenin supplementation on plasma adiponectin and neurogulin-4 (NRG-4) concentrations, metabolic parameters, and liver function indices in overweight/obese patients with NAFLD. METHODS AND ANALYSIS: This is a double-blind, randomized, placebo-controlled clinical study that will investigate the impacts of naringenin supplementation in overweight/obese patients with NAFLD. Liver ultrasonography will be applied to diagnose NAFLD. Forty-four eligible overweight/obese subjects with NAFLD will be selected and randomly assigned to receive naringenin capsules or identical placebo (each capsule contains 100 mg of naringenin or cellulose), twice daily for 4 weeks. Participants will be asked to remain on their usual diet and physical activity. Safety of naringenin supplementation was confirmed by the study pharmacist. The primary outcome of this study is changes in adiponectin circulating levels. The secondary outcomes include changes in NRG-4 levels, liver function indices, metabolic parameters, body weight, body mass index (BMI), waist circumference (WC), blood pressure, and hematological parameters. Statistical analysis will be conducted using the SPSS software (version 25), and P value less than 0.05 will be regarded as statistically significant. DISCUSSION: We hypothesize that naringenin administration may be useful for treating NAFLD by modulating energy balance, glucose and lipid metabolism, oxidative stress, and inflammation through different mechanisms. The current trial will exhibit the effects of naringenin, whether negative or positive, on NAFLD status. ETHICAL ASPECTS: The current trial received approval from the Medical Ethics Committee of Tehran University of Medical Sciences, Tehran, Iran (IR.TUMS.MEDICNE.REC.1399.439). TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT201311250155336N12 . Registered on 6 June 2020.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Suplementos Nutricionais , Método Duplo-Cego , Flavanonas , Humanos , Irã (Geográfico) , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
J Agric Food Chem ; 69(44): 13020-13033, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34723490

RESUMO

Phytoestrogens are strongly recommended for treating osteoporosis. Our previous study showed that naringin, a citrus flavonoid, can enhance the bone mass in ovariectomized rats. In this study, we further elucidated the mechanisms of naringin-induced osteoblast maturation and bone healing. Treatment of human osteoblasts with naringin increased cell viability and proliferation. In parallel, exposure to naringin enhanced translocation of estrogen receptor alpha (ERα) to nuclei and its transactivation activity. Sequentially, naringin induced alkaline phosphatase (ALP) mRNA and protein expression and its enzyme activity. Pretreatment with methylpiperidinopyrazole (MPP), a specific inhibitor of ERα, attenuated naringin-induced augmentations in ERα transactivation activity, ALP gene expression, and cell mineralization. The beneficial effects of naringin were also confirmed in mouse MC3T3-E1 cells. Moreover, administration of mice with a bone defect with naringin increased levels of ERα and ALP in damaged sites and simultaneously enhanced the healing rate and bone strength. Nevertheless, treatment with MPP weakened naringin-triggered expression of ERα and ALP and improved bone healing and mass. Therefore, naringin could improve osteoblast mineralization and bone healing via regulating ERα-dependent ALP gene expression. Naringin can be clinically applied for treatment of osteoporosis-related bone diseases.


Assuntos
Fosfatase Alcalina , Receptor alfa de Estrogênio , Fosfatase Alcalina/genética , Animais , Diferenciação Celular , Receptor alfa de Estrogênio/genética , Flavanonas , Expressão Gênica , Camundongos , Osteoblastos , Ratos
11.
Aging (Albany NY) ; 13(21): 23913-23935, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34731090

RESUMO

LianHuaQingWen (LHQW) improves clinical symptoms and alleviates the severity of COVID-19, but the mechanism is unclear. This study aimed to investigate the potential molecular targets and mechanisms of LHQW in treating COVID-19 using a network pharmacology-based approach and molecular docking analysis. The main active ingredients, therapeutic targets of LHQW, and the pathogenic targets of COVID-19 were screened using the TCMSP, UniProt, STRING, and GeneCards databases. According to the "Drug-Ingredients-Targets-Disease" network, Interleukin 6 (IL6) was identified as the core target, and quercetin, luteolin, and wogonin as the active ingredients of LHQW associated with IL6. The response to lipopolysaccharide was the most significant biological process identified by gene ontology enrichment analysis, and AGE-RAGE signaling pathway activation was prominent based on the interaction between LHQW and COVID-19. Protein-protein docking analysis showed that IL6 receptor (IL6R)/IL6/IL6 receptor subunit beta (IL6ST) and Spike protein were mainly bound via conventional hydrogen bonds. Furthermore, protein-small molecule docking showed that all three active ingredients could bind stably in the binding model of IL6R/IL6 and IL6ST. Our findings suggest that LHQW may inhibit the lipopolysaccharide-mediated inflammatory response and regulate the AGE-RAGE signaling pathway through IL6. In addition, the N-terminal domain of the S protein of COVID-19 has a good binding activity to IL6ST, and quercetin and wogonin in LHQW may affect IL6ST-mediated IL6 signal transduction and a large number of signaling pathways downstream to other cytokines by directly affecting protein-protein interaction. These findings suggest the potential molecular mechanism by which LHQW inhibits COVID-19 through the regulation of IL6R/IL6/IL6ST.


Assuntos
COVID-19 , Medicamentos de Ervas Chinesas/farmacologia , Produtos Finais de Glicação Avançada/metabolismo , Interleucina-6/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , SARS-CoV-2 , Antivirais/farmacologia , COVID-19/tratamento farmacológico , COVID-19/imunologia , Receptor gp130 de Citocina/metabolismo , Flavanonas/farmacologia , Humanos , Luteolina/farmacologia , Simulação de Acoplamento Molecular , Quercetina/farmacologia , Receptores de Interleucina-6/metabolismo , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo
12.
Toxicol Lett ; 352: 61-69, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34624459

RESUMO

Mitomycin treatment induces pulmonary toxicity, and alveolar epithelial cell senescence is crucial in the pathogenesis of the latter. However, the mechanism by which mitomycin induces alveolar epithelial cell senescence has yet to be elucidated. In this work, different doses (37.5-300 nM) of mitomycin induced the senescence of human alveolar type II-like epithelial cells and enhanced the phosphorylation of GSK3ß (S9). The GSK3ß (S9A) mutant reversed the senescence of mitomycin-treated alveolar epithelial cells. Pharmacological inhibition and gene deletion of Akt1, a kinase that regulates the phosphorylation of GSK3ß (S9), suppressed mitomycin-induced alveolar epithelial cell senescence. The knockdown of p53, a downstream effector of GSK3ß and an important regulator of cell senescence, repressed mitomycin-induced alveolar epithelial cell senescence. Treatment with baicalein weakened the phosphorylation of GSK3ß (S9) and alleviated the senescence of alveolar epithelial cells brought about by mitomycin treatment. GSK3ß (S9) phosphorylation appears to be the first signal involved in the mitomycin-induced senescence of alveolar epithelial cells and may present a potential target for attenuating mitomycin-induced pulmonary toxicity.


Assuntos
Alquilantes/toxicidade , Regulação para Baixo/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Mitomicina/toxicidade , Alvéolos Pulmonares/efeitos dos fármacos , Células A549 , Senescência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Flavanonas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/genética , Humanos , Imidazóis/farmacologia , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Alvéolos Pulmonares/citologia , Piridinas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
Molecules ; 26(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34641329

RESUMO

The antioxidant activity of food compounds is one of the properties generating the most interest, due to its health benefits and correlation with the prevention of chronic disease. This activity is usually measured using in vitro assays, which cannot predict in vivo effects or mechanisms of action. The objective of this study was to evaluate the in vivo protective effects of six phenolic compounds (naringenin, apigenin, rutin, oleuropein, chlorogenic acid, and curcumin) and three carotenoids (lycopene B, ß-carotene, and astaxanthin) naturally present in foods using a zebrafish embryo model. The zebrafish embryo was pretreated with each of the nine antioxidant compounds and then exposed to tert-butyl hydroperoxide (tBOOH), a known inducer of oxidative stress in zebrafish. Significant differences were determined by comparing the concentration-response of the tBOOH induced lethality and dysmorphogenesis against the pretreated embryos with the antioxidant compounds. A protective effect of each compound, except ß-carotene, against oxidative-stress-induced lethality was found. Furthermore, apigenin, rutin, and curcumin also showed protective effects against dysmorphogenesis. On the other hand, ß-carotene exhibited increased lethality and dysmorphogenesis compared to the tBOOH treatment alone.


Assuntos
Antioxidantes/administração & dosagem , Fatores Biológicos/administração & dosagem , Carotenoides/administração & dosagem , Polifenóis/administração & dosagem , Peixe-Zebra/embriologia , terc-Butil Hidroperóxido/efeitos adversos , Animais , Antioxidantes/farmacologia , Apigenina/administração & dosagem , Apigenina/farmacologia , Fatores Biológicos/farmacologia , Carotenoides/farmacologia , Curcumina/administração & dosagem , Curcumina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Flavanonas/administração & dosagem , Flavanonas/farmacologia , Licopeno/administração & dosagem , Licopeno/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/farmacologia , Xantofilas/administração & dosagem , Xantofilas/farmacologia , beta Caroteno/administração & dosagem , beta Caroteno/efeitos adversos , beta Caroteno/farmacologia
14.
Molecules ; 26(19)2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34641609

RESUMO

In recent years, the interest in the health-promoting effects of hop prenylflavonoids, especially its estrogenic effects, has grown. Unfortunately, one of the most potent phytoestrogens identified so far, 8-prenylnaringenin, is only a minor component of hops, so its isolation from hop materials for the production of estrogenically active food supplements has proved to be problematic. The aim of this study was to optimize the conditions (e.g., temperature, the length of the process and the amount of the catalyst) to produce 8-prenylnaringenin-rich material by the magnesium oxide-catalyzed thermal isomerization of desmethylxanthohumol. Under these optimized conditions, the yield of 8-prenylnaringenin was 29 mg per 100 gDW of product, corresponding to a >70% increase in its content relative to the starting material. This process may be applied in the production of functional foods or food supplements rich in 8-prenylnaringenin, which may then be utilized in therapeutic agents to help alleviate the symptoms of menopausal disorders.


Assuntos
Flavanonas/metabolismo , Flavonoides/metabolismo , Fitoestrógenos/metabolismo , Preparações de Plantas/metabolismo , Propiofenonas/metabolismo , Cerveja/análise , Catálise , Suplementos Nutricionais/análise , Flavanonas/química , Flavonoides/química , Humanos , Humulus/química , Óxido de Magnésio/química , Óxido de Magnésio/metabolismo , Fitoestrógenos/química , Extratos Vegetais/metabolismo , Preparações de Plantas/química , Propiofenonas/química , Temperatura
15.
Int J Mol Sci ; 22(17)2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34502526

RESUMO

Methylated flavonoids are promising pharmaceutical agents due to their improved metabolic stability and increased activity compared to unmethylated forms. The biotransformation in cultures of entomopathogenic filamentous fungi is a valuable method to obtain glycosylated flavones and flavanones with increased aqueous solubility and bioavailability. In the present study, we combined chemical synthesis and biotransformation to obtain methylated and glycosylated flavonoid derivatives. In the first step, we synthesized 2'-methylflavanone and 2'-methylflavone. Afterwards, both compounds were biotransformed in the cultures of two strains of entomopathogenic filamentous fungi Beauveria bassiana KCH J1.5 and Isaria fumosorosea KCH J2. We determined the structures of biotransformation products based on NMR spectroscopy. Biotransformations of 2'-methyflavanone in the culture of B. bassiana KCH J1.5 resulted in three glycosylated flavanones: 2'-methylflavanone 6-O-ß-d-(4″-O-methyl)-glucopyranoside, 3'-hydroxy-2'-methylflavanone 6-O-ß-d-(4″-O-methyl)-glucopyranoside, and 2-(2'-methylphenyl)-chromane 4-O-ß-d-(4″-O-methyl)-glucopyranoside, whereas in the culture of I. fumosorosea KCH J2, two other products were obtained: 2'-methylflavanone 3'-O-ß-d-(4″-O-methyl)-glucopyranoside and 2-methylbenzoic acid 4-O-ß-d-(4'-O-methyl)-glucopyranoside. 2'-Methylflavone was effectively biotransformed only by I. fumosorosea KCH J2 into three derivatives: 2'-methylflavone 3'-O-ß-d-(4″-O-methyl)-glucopyranoside, 2'-methylflavone 4'-O-ß-d-(4″-O-methyl)-glucopyranoside, and 2'-methylflavone 5'-O-ß-d-(4″-O-methyl)-glucopyranoside. All obtained glycosylated flavonoids have not been described in the literature until now and need further research on their biological activity and pharmacological efficacy as potential drugs.


Assuntos
Beauveria/metabolismo , Cordyceps/metabolismo , Flavanonas/metabolismo , Flavonas/metabolismo , Biotransformação
16.
Arq Bras Cardiol ; 117(2): 290-297, 2021 08.
Artigo em Inglês, Português | MEDLINE | ID: mdl-34495221

RESUMO

BACKGROUND: Nucleus tractus solitarius (NTS) is a brain area that plays a key role in kidney and cardiovascular regulation via baroreceptors impulses. OBJECTIVES: The aim of this study was to evaluate the effect of naringin (NAR) and trimetazidine (TMZ) alone and their combination on NTS electrical activity and baroreceptor sensitivity (BRS) in renal ischemia- reperfusion (I/R) injury. METHODS: Forty male Sprague-Dawley rats (200- 250 g) were allocated into 5 groups with 8 in each. 1) Sham; 2) I/R; 3) TMZ 5 mg/kg; 4) NAR 100 mg/kg; and 5) TMZ5+ NAR100. The left femoral vein was cannulated to infuse saline solution or drug and the BRS was evaluated. I/R was induced by occlusion of renal pedicles for 45 min, followed by 4 hours of reperfusion. The NTS local electroencephalogram (EEG) was recorded before, during ischemia and throughout the reperfusion. Phenylephrine was injected intravenously to evaluate BRS at the end of reperfusion time. The data were analyzed by two-way repeated measurement ANOVA followed by Tukey's post hoc test. A p-value <0.05 was considered significant. RESULTS: NTS electrical waves did not change during ischemia time, while they significantly decreased during the entire reperfusion time. NTS electrical activity and BRS dramatically reduced in rats with I/R injury; however, administration of NAR, TMZ alone or their combination significantly improved these changes in rats with I/R injury. CONCLUSIONS: The results showed that I/R injury leads to reduced BRS and NTS electrical activity and there may be an association between I/R and decreased BRS. In addition, NAR and TMZ are promising agents to treat I/R complications.


Assuntos
Traumatismo por Reperfusão , Trimetazidina , Animais , Barorreflexo , Flavanonas , Rim , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Núcleo Solitário , Trimetazidina/farmacologia
18.
J Agric Food Chem ; 69(40): 11890-11899, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34586803

RESUMO

Naringin, a natural flavonoid mainly found in citrus fruit, has been reported to exert a positive effect on improving skeletal muscle health. However, the effects and potential mechanisms of naringin on skeletal muscle fiber switching is still unclear. Here, we discovered that oral administration of naringin increased the low-speed running time, four-limb hanging time, body oxygen consumption in mice, enhanced aerobic enzyme activity, MyHC I expression, and slow-twitch fiber percentage in mice skeletal muscle. By contrast, naringin decreased α-GPDH enzyme activity, MyHC IIb expression, and fast-twitch fiber percentage. Moreover, naringin increased the concentration of serum adiponectin and activated the expression of AdipoR1, APPL1, AMPK, and PGC-1α. Furthermore, by the in vitro experiment and AdipoR1 knockdown, we found that inhibition of the AdipoR1 signaling pathway significantly reduced the effect of naringin on slow-twitch fiber-/fast-twitch fiber-related gene and protein expression. In conclusion, our results indicated that naringin could induce skeletal muscle fiber transition from fast twitch to slow twitch via the AdipoR1 signaling pathway. This study may provide new strategy for improving exercise endurance and slow muscle fiber deficiency-related diseases.


Assuntos
Proteínas Quinases Ativadas por AMP , Flavanonas , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Animais , Flavanonas/farmacologia , Camundongos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares de Contração Lenta/metabolismo , Músculo Esquelético/metabolismo , Transdução de Sinais
19.
J Agric Food Chem ; 69(40): 11926-11936, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34587738

RESUMO

People are at high risk of exposure to endogenous and exogenous acrolein (ACR). ACR can cause a multitude of illnesses, including cardiovascular disease, Alzheimer's disease, and diabetes. In this study, we investigated the reaction pathway of cardamonin (CAR) or alpinetin (ALP) with ACR and the interconversion of CAR and ALP in vitro at 37 °C in phosphate-buffered saline using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Subsequently, ACR adducts of CAR, ALP, and their metabolites, for example, CAR-ACR-1, ALP-ACR, mono-ACR-pinocembrin chalcone (PIN-ACR), and mono- and di-ACR-naringenin (NAR-ACR and NAR-2ACR), were detected in urine samples, but only CAR-ACR-1 and ALP-ACR were detected in fecal samples from the CAR- and ALP-treated mouse groups using ultraperformance liquid chromatography-MS/MS, respectively. Quantitative analyses showed that CAR, ALP, and their metabolites markedly scavenged ACR in a dose-dependent manner in vivo. Furthermore, we also found that the metabolites of CAR or ALP remained and promoted the ACR-trapping ability.


Assuntos
Acroleína , Espectrometria de Massas em Tandem , Animais , Chalconas , Cromatografia Líquida , Flavanonas , Camundongos
20.
Int J Mol Sci ; 22(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34576198

RESUMO

Helicobacter pylori (H. pylori) is a bacterium known to infect the human stomach. It can cause various gastrointestinal diseases including gastritis and gastric cancer. Hesperetin is a major flavanone component contained in citrus fruits. It has been reported to possess antibacterial, antioxidant, and anticancer effects. However, the antibacterial mechanism of hesperetin against H. pylori has not been reported yet. Therefore, the objective of this study was to determine the inhibitory effects of hesperetin on H. pylori growth and its inhibitory mechanisms. The results of this study showed that hesperetin inhibits the growth of H. pylori reference strains and clinical isolates. Hesperetin inhibits the expression of genes in replication (dnaE, dnaN, dnaQ, and holB) and transcription (rpoA, rpoB, rpoD, and rpoN) machineries of H. pylori. Hesperetin also inhibits the expression of genes related to H. pylori motility (flhA, flaA, and flgE) and adhesion (sabA, alpA, alpB, hpaA, and hopZ). It also inhibits the expression of urease. Hespereti n downregulates major virulence factors such as cytotoxin-associated antigen A (CagA) and vacuolating cytotoxin A (VacA) and decreases the translocation of CagA and VacA proteins into gastric adenocarcinoma (AGS) cells. These results might be due to decreased expression of the type IV secretion system (T4SS) and type V secretion system (T5SS) involved in translocation of CagA and VacA, respectively. The results of this study indicate that hesperetin has antibacterial effects against H. pylori. Thus, hesperetin might be an effective natural product for the eradication of H. pylori.


Assuntos
Helicobacter pylori/efeitos dos fármacos , Hesperidina/farmacologia , Neoplasias Gástricas/metabolismo , Proteínas de Bactérias/metabolismo , Western Blotting , Flavanonas/farmacologia , Infecções por Helicobacter/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Fatores de Virulência
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