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1.
Molecules ; 29(5)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38474439

RESUMO

The leaves of Chrysanthemum indicum L. are known to have various bioactive compounds; however, industrial use is extremely limited. To overcome this situation by producing high-quality leaves with high bioactive content, this study examined the environmental factors affecting the phytochemical content and antioxidant activity using C. indicum leaves collected from 22 sites in Kochi Prefecture, Japan. Total phenolic and flavonoid content in the dry leaves ranged between 15.0 and 64.1 (mg gallic acid g-1) and 2.3 and 11.4 (mg quercetin g-1), while the antioxidant activity (EC50) of the 50% ethanol extracts ranged between 28.0 and 123.2 (µg mL-1) in 1,1-Diphenyl-2-picrylhydrazyl radical scavenging assay. Among the identified compounds, chlorogenic acid and 1,5-dicaffeoylquinic acid were the main constituents in C. indicum leaves. The antioxidant activity demonstrated a positive correlation with 1,5-dicaffeoylquinic acid (R2 = 0.62) and 3,5-dicaffeoylquinic acid (R2 = 0.77). The content of chlorogenic acid and dicaffeoylquinic acid isomers varied significantly according to the effects of exchangeable magnesium, cation exchange capacity, annual temperature, and precipitation, based on analysis of variance. The habitat suitability map using the geographical information system and the MaxEnt model predicted very high and high regions, comprising 3.2% and 10.1% of the total area, respectively. These findings could be used in future cultivation to produce high-quality leaves of C. indicum.


Assuntos
Chrysanthemum , Cinamatos , Flavonoides , Flavonoides/química , Antioxidantes/química , Polifenóis/análise , Ácido Clorogênico/análise , Chrysanthemum/química , Folhas de Planta/química , Extratos Vegetais/química
2.
Biol Pharm Bull ; 46(11): 1535-1547, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37914356

RESUMO

The introduction of combined anti-retroviral therapy (cART) in 1996, along with a continual breakthrough in anti-human immunodeficiency virus-1 (HIV-1) drugs, has improved the life expectancies of HIV-1-infected individuals. However, the incidence of drug-resistant viruses between individuals undergoing cART and treatment-naïve individuals is a common challenge. Therefore, there is a requirement to explore potential drug targets by considering various stages of the viral life cycle. For instance, the late stage, or viral release stage, remains uninvestigated extensively in antiviral drug discovery. In this study, we prepared a natural plant library and selected candidate plant extracts that inhibited HIV-1 release based on our laboratory-established screening system. The plant extracts from Epilobium hirsutum L. and Chamerion angustifolium (L.) Holub, belonging to the family Onagraceae, decreased HIV-1 release and accelerated the apoptosis in HIV-1-infected T cells but not uninfected T cells. A flavonol glycoside quercetin with oenothein B in Onagraceae reduced HIV-1 release in HIV-1-infected T cells. Moreover, extracts from Chamerion angustifolium (L.) Holub and Senna alexandrina Mill. inhibited the infectivity of progeny viruses. Together, these results suggest that C. angustifolium (L.) Holub contains quercetin with oenothein B that synergistically blocks viral replication and kills infected cells via an apoptotic pathway. Consequently, the plant extracts from the plant library of Turkey might be suitable candidates for developing novel anti-retroviral drugs that target the late phase of the HIV-1 life cycle.


Assuntos
HIV-1 , Onagraceae , Humanos , Quercetina/farmacologia , Extratos Vegetais/farmacologia , Turquia , Apoptose
3.
Appl Environ Microbiol ; 89(11): e0100123, 2023 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-37874286

RESUMO

IMPORTANCE: Since the global market for sterols and vitamin D are grown with a high compound annual growth rate, a sustainable source of these compounds is required to keep up with the increasing demand. Thraustochytrid is a marine oleaginous microorganism that can synthesize several sterols, which are stored as SE in lipid droplets. DGAT2C is an unconventional SE synthase specific to thraustochytrids. Although the primary structure of DGAT2C shows high similarities with that of DGAT, DGAT2C utilizes sterol as an acceptor substrate instead of diacylglycerol. In this study, we examined more detailed enzymatic properties, intracellular localization, and structure-activity relationship of DGAT2C. Furthermore, we successfully developed a method to increase sterol and provitamin D3 productivity of thraustochytrid by more than threefold in the process of elucidating the function of the DGAT2C-specific N-terminal region. Our findings could lead to sustainable sterol and vitamin D production using thraustochytrid.


Assuntos
Esterol O-Aciltransferase , Esteróis , Gotículas Lipídicas , Vitamina D , Diacilglicerol O-Aciltransferase/genética
4.
Environ Res ; 231(Pt 2): 116207, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37244498

RESUMO

Dye-contaminated wastewaters from the printing batik industry are hazardous if discharged into the environment without any treatment. Finding an optimization and reusability assessment of a new fungal-material composite for dye-contaminated wastewater treatment is important for efficiency. The study purposes to optimize fungal mycelia Trametes hirsuta EDN 082 - light expanded clay aggregate (myco-LECA) composite for real priting batik dye wastewater treatment by using Response Surface Methodology with Central Composite Design (RSM-CCD). The factors included myco-LECA weight (2-6 g), wastewater volume (20-80 mL), and glucose concentration (0-10%) were applied for 144 h of incubation time. The result showed that the optimum condition was achieved at 5.1 g myco-LECA, at 20 mL wastewater, and at 9.1% glucose, respectively. In this condition, the decolorization values with an incubation time of 144 h were 90, 93, and 95%, at wavelengths 570, 620, and 670 nm, respectively. A reusability assessment was conducted for 19 cycles and the result showed that decolorization effectiveness was still above 96%. GCMS analysis showed the degradation of most compounds in the wastewater and the degradation products of the wastewater demonstrated detoxification against Vigna radiata and Artemia salina. The study suggests that myco-LECA composite has a good performance and therefore is a promising method for the treatment of printing batik wastewater.


Assuntos
Águas Residuárias , Purificação da Água , Argila , Biodegradação Ambiental , Trametes/metabolismo , Glucose/metabolismo , Corantes
5.
Sci Rep ; 13(1): 2386, 2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36765090

RESUMO

Biodegradable plastics can solve the problem of unwanted plastics accumulating in the environment if they can be given the contradictory properties of durability in use and rapid degradation after use. Commercially available agricultural biodegradable mulch films are made from formulations containing polybutylene adipate-co-terephthalate (PBAT) to provide mechanical and UV resistance during the growing season. Although used films are ploughed into the soil using a tiller to promote decomposition, it is difficult if they remain durable. We showed that an enzyme produced by the leaf surface yeast Pseudozyma antarctica (PaE) degrades PBAT-containing films. In laboratory studies, PaE randomly cleaved the PBAT polymer chain and induced erosion of the film surface. In the field, commercial biodegradable films containing PBAT placed on ridges were weakened in both the warm and cold seasons by spraying the culture filtrate of P. antarctica. After the field was ploughed the next day, the size and total weight of residual film fragments decreased significantly (p < 0.05). Durable biodegradable plastics used in the field are degraded using PaE treatment and are broken down into small fragments by the plough. The resultant degradation products can then be more readily assimilated by many soil microorganisms.


Assuntos
Plásticos Biodegradáveis , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Polímeros/metabolismo , Solo , Agricultura
6.
Cancer Immunol Immunother ; 71(11): 2743-2755, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35429246

RESUMO

The aim of this study was to determine the efficacy and the biomarkers of the CHP-NY-ESO-1 vaccine complexed with full-length NY-ESO-1 protein and a cholesteryl pullulan (CHP) in patients with esophageal squamous cell carcinoma (ESCC) after surgery. We conducted a randomized phase II trial. Fifty-four patients with NY-ESO-1-expressing ESCC who underwent radical surgery following cisplatin/5-fluorouracil-based neoadjuvant chemotherapy were assigned to receive either CHP-NY-ESO-1 vaccination or observation as control. Six doses of CHP-NY-ESO-1 were administered subcutaneously once every two weeks, followed by nine more doses once every four weeks. The endpoints were disease-free survival (DFS) and safety. Exploratory analysis of tumor tissues using gene-expression profiles was also performed to seek the biomarker. As there were no serious adverse events in 27 vaccinated patients, we verified the safety of the vaccine. DFS in 2 years were 56.0% and 58.3% in the vaccine arm and in the control, respectively. Twenty-four of 25 patients showed NY-ESO-1-specific IgG responses after vaccination. Analysis of intra-cohort correlations among vaccinated patients revealed that 5% or greater expression of NY-ESO-1 was a favorable factor. Comprehensive analysis of gene expression profiles revealed that the expression of the gene encoding polymeric immunoglobulin receptor (PIGR) in tumors had a significantly favorable impact on outcomes in the vaccinated cohort. The high PIGR-expressing tumors that had higher NY-ESO-1-specific IgA response tended to have favorable prognosis. These results suggest that PIGR would play a major role in tumor immunity in an antigen-specific manner during NY-ESO-1 vaccinations. The IgA response may be relevant.


Assuntos
Vacinas Anticâncer , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Receptores de Imunoglobulina Polimérica , Anticorpos Antineoplásicos , Antígenos de Neoplasias , Cisplatino , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Fluoruracila , Glucanos , Humanos , Imunoglobulina A , Imunoglobulina G , Proteínas de Membrana , Prognóstico
7.
J Med Chem ; 65(4): 3460-3472, 2022 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-35113551

RESUMO

Three new diterpenes, stellejasmins A (1) and B (2) and 12-O-benzoylphorbol-13-heptanoate (3), were isolated from the roots of Stellera chamaejasme L. The structures of 1-3 were elucidated by extensive NMR and mass spectroscopic analyses. Compounds 1 and 2 are the first derivatives containing a hydroxy group at C-2 in the family of daphnane and tigliane diterpenes. The presence of a chlorine atom in 1 is unique in the plant metabolite. Compound 3 has an odd-number acyl group, which is biosynthetically notable. Human immunodeficiency virus (HIV) LTR-driven transcription activity was tested with 1-3 and 17 known diterpenes isolated from S. chamaejasme L. and Wikstroemia retusa A.Gray. Among these, gnidimacrin (4), stelleralide A (5), and wikstroelide A (20) were highly potent, with EC50 values of 0.14, 0.33, and 0.39 nM, respectively. The structure-activity relationship (SAR) was investigated using 20 natural and eight synthetic diterpenes. This is the first SAR study on natural daphnane and tigliane diterpenes.


Assuntos
Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/farmacologia , Diterpenos/síntese química , Diterpenos/farmacologia , HIV/efeitos dos fármacos , Forbóis/química , Latência Viral/efeitos dos fármacos , Diterpenos/química , Modelos Moleculares , Simulação de Acoplamento Molecular , Forbóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Relação Estrutura-Atividade , Thymelaeaceae/química , Wikstroemia/química
8.
Bioorg Med Chem Lett ; 59: 128566, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35063633

RESUMO

The ubiquitin-proteasome system (UPS) regulates selective protein degradation to maintain protein homeostasis. Small molecules that inhibit the UPS-dependent protein degradation are promising anti-tumor agents. We report a cell-based luminescent assay using HeLa cells expressing luciferase-fused oxygen-dependent destruction domain (ODD) of hypoxia-inducible factor 1 α (HIF-1 α). ODD is degraded by the UPS and this assay system can aid in the identification of natural products that inhibit either process of the UPS, including ubiquitination/deubiquitination and proteasomal degradation. This reporter assay can exclude the influences of coloring or fluorescent compounds in extracts, thereby leading to effective high-throughput processing. The screening of 15,025 extracts of natural sources identified the culture extract of the fungus Remotididymella sp. (18F02908). Bioassay-guided isolation yielded two new polyketides, mellains A (1) and B (2), together with leptosphaerodione (3) and its acetone adduct 4. Compound 1 was revealed to have an unprecedented benzo[g]isoquinoline-8,10-dione skeleton. Evaluation of the biological activities demonstrated that these polyketides inhibit the proteasomal proteolysis. This is the first report of the identification of proteasome inhibitors from natural sources using a cell-based reporter assay targeting UPS inhibitors.


Assuntos
Ascomicetos/química , Produtos Biológicos/farmacologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Células HeLa , Humanos , Estrutura Molecular , Inibidores de Proteassoma/química , Inibidores de Proteassoma/isolamento & purificação , Relação Estrutura-Atividade
9.
Appl Environ Microbiol ; 87(23): e0026821, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34524902

RESUMO

Glycerol is an eco-friendly solvent that enhances plant biomass decomposition via glycerolysis in many pretreatment methods. Nonetheless, inefficient conversion of glycerol to ethanol by natural Saccharomyces cerevisiae limits its use in these processes. In this study, we have developed an efficient glycerol-converting yeast strain by genetically modifying the oxidation of cytosolic NAD (NADH) by an O2-dependent dynamic shuttle and abolishing both glycerol phosphorylation and biosynthesis in S. cerevisiae strain D452-2, as well as by vigorous expression of whole genes in the dihydroxyacetone (DHA) pathway (Candida utilis glycerol facilitator, Ogataea polymorpha glycerol dehydrogenase, endogenous dihydroxyacetone kinase, and triosephosphate isomerase). The engineered strain showed conversion efficiencies (CE) up to 0.49 g ethanol/g glycerol (98% of theoretical CE), with a production rate of >1 g liter-1 h-1 when glycerol was supplemented in a single fed-batch fermentation in a rich medium. Furthermore, the engineered strain converted a mixture of glycerol and glucose into bioethanol (>86 g/liter) with 92.8% CE. To the best of our knowledge, this is the highest reported titer of bioethanol produced from glycerol and glucose. Notably, we developed a glycerol-utilizing transformant from a parent strain which cannot utilize glycerol as a sole carbon source. The developed strain converted glycerol to ethanol with a productivity of 0.44 g liter-1 h-1 on minimal medium under semiaerobic conditions. Our findings will promote the utilization of glycerol in eco-friendly biorefineries and integrate bioethanol and plant oil industries. IMPORTANCE With the development of efficient lignocellulosic biorefineries, glycerol has attracted attention as an eco-friendly biomass-derived solvent that can enhance the dissociation of lignin and cell wall polysaccharides during the pretreatment process. Coconversion of glycerol with the sugars released from biomass after glycerolysis increases the resources for ethanol production and lowers the burden of component separation. However, low conversion efficiency from glycerol and sugars limits the industrial application of this process. Therefore, the generation of an efficient glycerol-fermenting yeast will promote the applicability of integrated biorefineries. Hence, metabolic flux control in yeast grown on glycerol will lead to the generation of cell factories that produce chemicals, which will boost biodiesel and bioethanol industries. Additionally, the use of glycerol-fermenting yeast will reduce global warming and generation of agricultural waste, leading to the establishment of a sustainable society.


Assuntos
Etanol , Glicerol , Saccharomyces cerevisiae , Etanol/metabolismo , Glucose , Glicerol/metabolismo , Microbiologia Industrial , Microrganismos Geneticamente Modificados , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Solventes , Açúcares
10.
Indian J Clin Biochem ; 36(3): 375-377, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34220015

RESUMO

HLA association with drug-induced liver injury has recently been pointed out about multiple medicines. The aim of this study was to evaluate relationship between HLA gene and liver injury related to Baikal skullcap-containing Kampo medicines (BSCK). We previously examined HLA genes in 3 cases of BSCK-induced liver injury. Recently we could encounter 2 cases diagnosed as "definitely-related case" of BSCK-induced liver injury. HLA genes of the 2 cases were analyzed by Sequencing Based Typing method with Next Generation Sequencer at HLA Laboratory in Kyoto. HLA-DPA1*02:02:02 and DPB1*05:01:01 were observed in the 2 cases: concordance was not observed in HLA-A, B, C, DRB1, DRB4, DQA1, or DQB1. The previous 3 cases of BSCK-induced liver injury had the same allele type to the 2 cases only in HLA-DPA1. Putting all these together, HLA-DPA1*02:02:02 was observed in common among 5 cases of BSCK-induced liver injury. HLA-DPA1*02:02:02 is possibly associated with BSCK-induced liver injury.

11.
J Pediatr Surg ; 56(7): 1117-1120, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33896618

RESUMO

BACKGROUND/PURPOSE: therapeutic strategy for meconium-related ileus (MRI) in very-low-birth-weight infants (VLBWs) has not been established. This study aims to clarify the optimum therapeutic strategy for MRI in VLBWs. METHODS: MRI was defined as delayed meconium excretion and microcolon on contrast enema with Gastrografin (diatrizoate acid). Forty-two infants with MRI were treated at our institution between 2009 and 2019, and are reviewed here. They were classified into two groups: in group A (n=21), Gastrografin regurgitated into the dilated intestine during the first or second round of Gastrografin enema (GaE), while in group B (N = 21), Gastrografin did not regurgitate. Laparotomy was indicated if the intestine was perforated, or if abdominal distention was not relieved by two rounds of GaE. RESULTS: in group A, meconium was excreted in all cases within 24 h after GaE, and no cases required laparotomy. In group B, twelve cases (57%) underwent laparotomy (P < 0.01), six cases in this group (29%), showed free air on X-ray images (P < 0.01). The median hospital stay in groups A and B were 89.0 and 136.5 days, respectively (P < 0.05). Overall mortality was 2.4%. CONCLUSIONS: early therapeutic diagnosis by GaE followed by early surgery is suggested as the optimum strategy for MRI in VLBWs.


Assuntos
Íleus , Obstrução Intestinal , Íleo Meconial , Diatrizoato de Meglumina , Enema , Humanos , Íleus/etiologia , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Mecônio
12.
Molecules ; 25(23)2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33255802

RESUMO

The growth and quality of licorice depend on various environmental factors, including the local climate and soil properties; therefore, its cultivation is often unsuccessful. The current study investigated the key factors that affect the contents of bioactive compounds of Glycyrrhiza glabra L. root and estimated suitable growth zones from collection sites in the Hatay region of Turkey. The contents of three bioactive compounds (glycyrrhizic acid, glabridin, and liquiritin), soil factors (pH, soil bearing capacity, and moisture content), and geographical information (slope, aspect, curvature, elevation, and hillshade) were measured. Meteorological data (temperature and precipitation) were also obtained. An analysis of variance (ANOVA) and multivariate analysis of variance (MANOVA) were performed on the data. The soil bearing capacity, moisture content, slope, aspect, curvature, and elevation of the study area showed statistically significant effects on the glycyrrhizic acid and liquiritin contents. A habitat suitability zone map was generated using a GIS-based frequency ratio (FR) model with spatial correlations to the soil, topographical, and meteorological data. The final map categorized the study area into four zones: very high (15.14%), high (31.50%), moderate (40.25%), and low suitability (13.11%). High suitability zones are recommended for further investigation and future cultivation of G. glabra.


Assuntos
Ecossistema , Glycyrrhiza/química , Compostos Fitoquímicos/química , Extratos Vegetais/química , Cromatografia Líquida de Alta Pressão , Geografia , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Curva ROC , Solo/química , Turquia
13.
Fitoterapia ; 146: 104714, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32858173

RESUMO

Four new guaiane-type sesquiterpenes, chamaejasmins A-D (1-4), were isolated from the root of Stellera camaejasme L. collected in Nepal, together with two known terpenes, stelleraguaianone B (5) and 1α,7α,10αH-guaia-4,11-dien-3-one (6). The structures of 1-4 including their absolute configurations were determined by extensive 2D NMR analyses, mass spectroscopy, and TDDFT calculations of their 13C chemical shifts and ECD spectra. Chamaejasmin A (1) showed cytotoxicity against HeLa cells with an IC50 value of 6.3 µM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Flavonoides/farmacologia , Sesquiterpenos de Guaiano/farmacologia , Thymelaeaceae/química , Antineoplásicos Fitogênicos/isolamento & purificação , Flavonoides/isolamento & purificação , Células HeLa , Humanos , Estrutura Molecular , Nepal , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Sesquiterpenos de Guaiano/isolamento & purificação
14.
J Altern Complement Med ; 26(4): 329-334, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31977240

RESUMO

Objective: The development of pseudoaldosteronism is shown to be mainly associated with four factors: daily dose of glycyrrhiza (licorice), duration of glycyrrhiza use, body size, and age. Recently, direct bilirubinemia and hypoalbuminemia are newly reported as possible factors that trigger pseudoaldosteronism due to glycyrrhiza ingestion. Pseudoaldosteronism occurs in the presence of combinations of these factors; therefore, the importance of each factor on the tolerance to glycyrrhiza loading is still unclear. Methods: In seven patients (63-78 years old, six women) who developed pseudoaldosteronism due to ingestion of glycyrrhiza-containing Kampo extract in their clinic, serum albumin and direct bilirubin (D-bil) levels were investigated. In six women, the authors evaluated the correlations between daily dose of glycyrrhiza ingested and each factor: age, height, weight, body mass index, body surface area (BSA), and duration of ingestion (Pearson's correlation coefficient). Results: No patients had abnormal levels of serum albumin or D-bil around the time of the onset. In six women, the highest correlation coefficient was observed between BSA and the glycyrrhiza dose in Kampo extract at the onset of pseudoaldosteronism. Conclusions: The findings suggested that in elderly women, BSA should be considered first as a factor for predicting the development of pseudoaldosteronism.


Assuntos
Glycyrrhiza/efeitos adversos , Síndrome de Liddle/induzido quimicamente , Medicina Kampo/efeitos adversos , Extratos Vegetais/efeitos adversos , Idoso , Bilirrubina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Albumina Sérica Humana
15.
BMC Psychiatry ; 19(1): 394, 2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31830951

RESUMO

BACKGROUND: Somatization is regarded as psychological or emotional distress in the form of physical symptoms that are otherwise medically unexplained. CASE PRESENTATION: We report a case of a patient with a somatic symptom disorder (SSD) and depression who was later diagnosed with anterior cutaneous nerve entrapment syndrome (ACNES) when Carnett's test was positive and block anesthesia using trigger point injections dramatically improved the symptom of abdominal pain. CONCLUSION: We concluded that the differentiation of SSDs, such as psychogenic pain, from ACNES is very difficult. Psychiatrists should be aware of this syndrome.


Assuntos
Sintomas Inexplicáveis , Síndromes de Compressão Nervosa/diagnóstico , Síndromes de Compressão Nervosa/psicologia , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Dor Abdominal/psicologia , Adolescente , Diagnóstico Diferencial , Feminino , Humanos , Transtornos Mentais/complicações , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia
16.
Elife ; 82019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793879

RESUMO

Lysosomal acidification is a key feature of healthy cells. Inability to maintain lysosomal acidic pH is associated with aging and neurodegenerative diseases. However, the mechanisms elicited by impaired lysosomal acidification remain poorly understood. We show here that inhibition of lysosomal acidification triggers cellular iron deficiency, which results in impaired mitochondrial function and non-apoptotic cell death. These effects are recovered by supplying iron via a lysosome-independent pathway. Notably, iron deficiency is sufficient to trigger inflammatory signaling in cultured primary neurons. Using a mouse model of impaired lysosomal acidification, we observed a robust iron deficiency response in the brain, verified by in vivo magnetic resonance imaging. Furthermore, the brains of these mice present a pervasive inflammatory signature associated with instability of mitochondrial DNA (mtDNA), both corrected by supplementation of the mice diet with iron. Our results highlight a novel mechanism linking impaired lysosomal acidification, mitochondrial malfunction and inflammation in vivo.


Assuntos
Ácidos/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Deficiências de Ferro , Lisossomos/metabolismo , Animais , Apoptose , Encéfalo/metabolismo , Hipóxia Celular/efeitos dos fármacos , Proliferação de Células , DNA Mitocondrial/genética , Modelos Animais de Doenças , Transporte de Elétrons , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Homeostase , Concentração de Íons de Hidrogênio , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imunidade Inata , Inflamação/genética , Ferro/farmacologia , Lisossomos/efeitos dos fármacos , Camundongos , Mitocôndrias/metabolismo , Biogênese de Organelas , ATPases Vacuolares Próton-Translocadoras/antagonistas & inibidores , ATPases Vacuolares Próton-Translocadoras/metabolismo , alfa-Glucosidases/deficiência , alfa-Glucosidases/metabolismo
17.
Molecules ; 24(21)2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31731511

RESUMO

Despite the development of a range of anti-cancer agents, cancer diagnoses are still increasing in number, remaining a leading cause of death. Anticancer drug treatment is particularly important for leukemia. We screened Turkish plants and found the unique antileukemic activity of twig components in Turkish Caucasian beech, selectively inducing apoptosis in leukemia cells. This effect is unique among some kinds of beeches, presumably related to oxidative stress. This study would lead to effective use of discarded material, i.e., twig of beech, and a new anti-leukemic drug based on large tree.


Assuntos
Fagus/química , Leucemia/tratamento farmacológico , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Extratos Vegetais/química , Folhas de Planta/química , Árvores/química
18.
J Food Biochem ; 43(6): e12813, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31353615

RESUMO

Chronic neuroinflammation is reported to be associated in the progression of many neurodegenerative diseases and there is an increasing interest for the natural products as neuroprotective and anti-neuroinflammatory agents. In present research, we evaluated the potential inhibitory effects of extract, fractions, and isolated compounds from Citrus 'Hebesu' on lipopolysaccharide (LPS)-induced inflammatory responses using BV-2 murine microglial cells. The dried methanol extract (CH) was suspended in water and partitioned with hexane and ethyl acetate to give hexane soluble (CHH), ethyl acetate soluble (CHE), and water soluble (CHW) fractions. The extract (CH) and fractions CHH and CHE inhibited the expression of mRNA encoding pro-inflammatory cytokine interleukin (IL)-1ß. CHE and CHH were further purified by various column chromatographic methods to obtain hesperidin (1), tangeretin (2), 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone (3), 3,5,6,7,8,3',4'-heptamethoxyflavone (4), nobiletin (5), 3,4,5-trimethoxy-trans-cinnamic alcohol (6), and meranzin hydrate (7). Among them, three polymethoxyflavonoids, 3, 4, and 5 significantly inhibited the expression of IL-1ß mRNA. PRACTICAL APPLICATIONS: Citrus 'Hebesu' is a local cultivar in Hyuga City, Miyazaki prefecture, Japan and its immature fruits are consumed with different food recipes. Till now, there is no detailed study on the chemical constituents and anti-neuroinflammatory activity of this cultivar. In this study, seven compounds were isolated from the peels of immature fruits. Methanol extract, hexane, and ethyl acetate fractions and three polymethoxyflavonoids showed a significant inhibitory activity against expression of IL-1ß mRNA. Consumption of peels of Citrus 'Hebesu' might play important role in the prevention and treatment of neurodegenerative diseases, however, detailed mechanism based in vivo studies are necessary in future for providing more scientific evidences.


Assuntos
Citrus/química , Flavonoides/farmacologia , Frutas/química , Microglia/efeitos dos fármacos , Extratos Vegetais , Animais , Anti-Inflamatórios , Linhagem Celular , Expressão Gênica/efeitos dos fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Camundongos , Microglia/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/prevenção & controle , Extratos Vegetais/análise , Extratos Vegetais/farmacologia
19.
Nat Prod Res ; 33(11): 1670-1673, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29334238

RESUMO

Flowers of Citrus plants are used as mild sedatives and for the treatment of insomnia in traditional medicines. In Japan, tea made from the flowers of Satsuma mandarin is consumed as healthy drink. Hesperidin (1), hesperetin (2), rutin (3), quercetin (4), nicotiflorin (5), eriocitrin (6), narirutin (7), phenylethyl glucoside (8) and unshuoside A (9) were isolated from the MeOH extract of fresh flowers. Structure elucidation of these compounds was performed on the basis of NMR spectroscopic data. Among them, rutin (3), quercetin (4) and eriocitrin (6) showed potent free radical scavenging activity, whereas hesperetin (2) and quercetin (4) showed potent α-glucosidase inhibitory activity.


Assuntos
Citrus/química , Flores/química , Sequestradores de Radicais Livres/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Flavonoides/análise , Flavonoides/química , Sequestradores de Radicais Livres/química , Inibidores de Glicosídeo Hidrolases/química , Hesperidina/análise , Hesperidina/química , Japão , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Fenóis/análise , Fenóis/química , Plantas Medicinais/química , Quercetina/análise , Quercetina/química , Rutina/análise , Rutina/química
20.
BMC Complement Altern Med ; 18(1): 282, 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30340582

RESUMO

BACKGROUND: Lifestyle-related diseases such as diabetes are steadily increasing worldwide. In Sudan, there are a variety of plant species used traditionally for the treatment of diabetes, obesity and other symptoms which need to be validated through scientific studies for their claimed traditional uses. Therefore, in the current study, the free radical scavenging activity, α-glucosidase inhibitory and pancreatic lipase inhibitory activities of 70% ethanol and water extracts of eighteen Sudanese medicinal plants were investigated using various in vitro assays. Moreover, the cytotoxicity and genotoxicity were assessed for the bioactive plant extracts. METHODS: Eighteen plants were selected on the basis of their traditional uses and extracted with 70% ethanol and water to obtain thirty-six extracts. The obtained extracts were screened using different in vitro bioassays namely, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, α-glucosidase inhibitory and pancreatic lipase inhibitory assays. Furthermore, the active plant extracts were investigated for their cytotoxicity and genotoxicity on HeLa cell line using HCS DNA Damage Assay. RESULTS: Both 70% ethanol and water extracts of Acacia nilotica, Ziziphus spina-christi, Abrus precatorius, and Geigeria alata along with the 70% ethanol extract of Martynia annua showed potent free radical scavenging activity. Regarding the α-glucosidase inhibition assay, both extracts of Acacia nilotica, Ziziphus spina-christi, Geigeria alata, and Cyperus rotundus showed potent activity. In general, 70% ethanol extracts were more potent compared to water extracts with exception of Cordia sinensis and Cymbopogon proximus, for which water extracts also showed potent enzyme inhibitory activity. Similarly, water extracts of Acacia nilotica and Ziziphus spina-christi showed potent inhibitory activity against pancreatic lipase enzyme. Some of the extracts also showed significant genotoxicity and cytotoxicity at the concentration range used for bioactivities. CONCLUSION: The extracts of Acacia nilotica, Ziziphus spina-christi, Geigeria alata, Martynia annua and Abrus precatorius exhibited an appreciable range of activity on antioxidant and enzyme inhibitory assays.


Assuntos
Antioxidantes/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Lipase/antagonistas & inibidores , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Compostos de Bifenilo , Sobrevivência Celular/efeitos dos fármacos , Células HeLa , Humanos , Picratos , Extratos Vegetais/toxicidade , Sudão
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