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1.
Anal Chim Acta ; 1183: 338938, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34627522

RESUMO

The spiropyran (SP) compound is a typical photochromic compound. Its merocyanine configuration (MC) can accept energy and be excited by visible light, while the closed-loop configuration cannot. In this work, the SP was wrapped in ß-cyclodextrin (ß-CD-SP) firstly. When it was competitively replaced by thiamethoxam and dissociated out of ß-CD, it would be converted to MC, which could be excited by visible light around 550 nm to produce red fluorescence. Here, CsPbBr3 was selected as the energy donor based on the principle of fluorescence resonance energy transfer (FRET). In order to connect with ß-CD-SP and improve its stability, CsPbBr3 was wrapped in mesoporous silica, and then the second wrapping was performed to block those mesopores and the amination reaction was carried out (NH2-SiO2@CsPbBr3). Subsequently, NH2-SiO2@CsPbBr3 with green fluorescence (506 nm) was used as the internal standard and excitation light source for MC, and the red fluorescence of MC was used as the response signal to construct a ratiometric fluorescence sensor. When thiamethoxam was added and excited by 365 nm ultraviolet light, the energy would be transferred from NH2-SiO2@CsPbBr3 (506 nm) that emitted green fluorescence to MC, which emitted red fluorescence. So, the fluorescence color changed from green to yellow to red with the addition of the thiamethoxam. This sensor was employed to detect thiamethoxam in soil and yam.


Assuntos
Transferência Ressonante de Energia de Fluorescência , Dióxido de Silício , Benzopiranos , Indóis , Nitrocompostos , Tiametoxam
2.
Environ Monit Assess ; 193(11): 727, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34655328

RESUMO

Twenty-nine surface sediments from Chaohu Lake in China and from its six main tributaries were sampled to investigate the concentrations of two important polycyclic musks (PCMs), 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta(g)-2-benzopyran (galaxolide, HHCB) and 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (tonalide, AHTN), as well as the concentration of 4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta(g)-2-benzopyran-1-one (galaxolidon, HHCB-lactone), which is the main degradation product of HHCB. Except for the high concentrations of AHTN and HHCB measured in the Nanfei River (879 ng/g dw and 5,513 ng/g dw, respectively), the levels of AHTN and HHCB in the river sediments were 7.08-44.9 ng/g dw and 20.6-268 ng/g dw, respectively, which are slightly lower than those documented in various areas worldwide. The concentrations of AHTN and HHCB in the sediments of Chaohu Lake were one or two orders of magnitude lower than those in the tributary rivers and showed a clear regional distribution. The concentrations of HHCB-lactone were comparable to those of HHCB and presented a significant positive correlation with the concentrations of HHCB, suggesting that the HHCB-lactone originated directly from the degradation of HHCB in wastewater treatment plants (WWTPs) or in the natural environment. The diagnostic ratios of HHCB/AHTN and HHCB-lactone/HHCB and the enantiomeric fractions (EFs) of these PCMs showed that the direct origins of the target PCMs in the study area were municipal and industrial wastewaters discharged from adjacent cities or point sources and that the HHCB-lactone in sediment originated from the natural degradation of HHCB in the rivers and the lake. The results of the risk assessment showed that the PCMs in the watershed sediments were unlikely to pose a threat to aquatic species. However, the effluents of industrial and municipal wastewaters that are discharged into the Nanfei River should be investigated in future research.


Assuntos
Lagos , Poluentes Químicos da Água , Benzopiranos/análise , China , Monitoramento Ambiental , Lactonas , Rios , Poluentes Químicos da Água/análise
3.
J Hazard Mater ; 416: 126116, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492911

RESUMO

Galaxolide (HHCB), one of the most widely used synthetic musks in personal care products (PCPs), has been recognized as an emerging contaminant with potential human health concerns. To overcome such adverse effects, a systematic molecular design, screening and performance evaluation approach was developed to generate functionally improved and environmentally friendly HHCB derivatives. Among the 90 designed HHCB derivatives, 15 were screened with improved functional properties (i.e., odor stability and intensity) and less environmental impacts (i.e., lower bio-toxicity, bio-accumulation ability, and mobility) using 3D-QSAR models and density functional theory methods. Their human health risks were then assessed by toxicokinetic analysis, which narrowed the candidates to four. Derivative 7, the designed molecule with the least dermal adsorption potential, was evaluated for its interaction with other PCPs additives (i.e., anti-photosensitivity materials and moisturizer) and such impacts on human health risks using molecular docking and molecular dynamic simulation. The environmental fate of Derivative 7 after transformation (i.e., photodegradation, biotransformation, and chlorination) was also discussed. Biotransformation and chlorination were recognized as optimum options for Derivative 7 mitigation. This study provided the theoretical basis for the design of functionally improved and environmentally friendly HHCB alternatives and advanced the understanding of their environmental behaviors and health risks.


Assuntos
Cosméticos , Relação Quantitativa Estrutura-Atividade , Benzopiranos , Biotransformação , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular
4.
J Org Chem ; 86(19): 13693-13701, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34529434

RESUMO

A transition-metal-free postmodification of the Groebke-Blackburn-Bienaymé (GBB) reaction for the synthesis of spiro[chromene-imidazo[1,2-a]pyridin]-3'-imine was discovered. The unusual transformation represents the first example of activation and the reaction of the imidazole carbon atom. In this postcondensational modification, KOt-Bu acts as a base, which, after the isomerization of an alkyne moiety to allene, causes the next unique nucleophilic reaction of the imidazole carbon atom that results in spirocyclic structures. The proposed reaction mechanism was confirmed based on the DFT calculations.


Assuntos
Iminas , Elementos de Transição , Alcinos , Benzopiranos , Ciclização
5.
Nat Commun ; 12(1): 5321, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493732

RESUMO

CARM1 is often overexpressed in human cancers including in ovarian cancer. However, therapeutic approaches based on CARM1 expression remain to be an unmet need. Cancer cells exploit adaptive responses such as the endoplasmic reticulum (ER) stress response for their survival through activating pathways such as the IRE1α/XBP1s pathway. Here, we report that CARM1-expressing ovarian cancer cells are selectively sensitive to inhibition of the IRE1α/XBP1s pathway. CARM1 regulates XBP1s target gene expression and directly interacts with XBP1s during ER stress response. Inhibition of the IRE1α/XBP1s pathway was effective against ovarian cancer in a CARM1-dependent manner both in vitro and in vivo in orthotopic and patient-derived xenograft models. In addition, IRE1α inhibitor B-I09 synergizes with immune checkpoint blockade anti-PD1 antibody in an immunocompetent CARM1-expressing ovarian cancer model. Our data show that pharmacological inhibition of the IRE1α/XBP1s pathway alone or in combination with immune checkpoint blockade represents a therapeutic strategy for CARM1-expressing cancers.


Assuntos
Carcinoma Epitelial do Ovário/terapia , Endorribonucleases/genética , Neoplasias Ovarianas/terapia , Receptor de Morte Celular Programada 1/genética , Proteína-Arginina N-Metiltransferases/genética , Proteínas Serina-Treonina Quinases/genética , Proteína 1 de Ligação a X-Box/genética , Animais , Anticorpos Monoclonais/farmacologia , Sequência de Bases , Benzopiranos/farmacologia , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/imunologia , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular Tumoral , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Endorribonucleases/antagonistas & inibidores , Endorribonucleases/imunologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Himecromona/análogos & derivados , Himecromona/farmacologia , Inibidores de Checkpoint Imunológico , Camundongos , Terapia de Alvo Molecular , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Ligação Proteica , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Proteína-Arginina N-Metiltransferases/imunologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/imunologia , Transdução de Sinais , Proteína 1 de Ligação a X-Box/antagonistas & inibidores , Proteína 1 de Ligação a X-Box/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
6.
J Agric Food Chem ; 69(36): 10709-10721, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34476938

RESUMO

Thirty-one new 4H-chromene derivatives were designed and synthesized. Their structures were identified with IR, 1H NMR, 13C NMR, and HRMS. The crystal structure of compound 2a was determined by single-crystal X-ray diffraction. Their antifungal activities were evaluated against Pyricularia oryzae, Erysiphe graminis, Coniella diplodiella, Pseudoperonospora cubensis, and Sclerotinia sclerotiorum. These results demonstrated that most compounds exhibited remarkable inhibitory activities at 20 µg/mL. Compounds 4b and 4c displayed excellent antifungal activity against S. sclerotiorum and possessed better efficacy than fluopyram. At the same time, the inhibitory activity of the bioactive compounds was evaluated against succinate dehydrogenase (SDH). The results showed that these compounds possessed outstanding activity. Compounds 4b and 4c displayed better inhibitory activity than fluopyram. The molecular modeling results revealed that compound 4c had stronger affinity to SDH than fluopyram. It is the first time that the inhibitory activity of 4H-chromene analogs against SDH has been reported.


Assuntos
Benzopiranos , Succinato Desidrogenase , Antifúngicos/farmacologia , Ascomicetos , Benzopiranos/farmacologia , Estrutura Molecular , Relação Estrutura-Atividade , Succinato Desidrogenase/metabolismo
7.
J Enzyme Inhib Med Chem ; 36(1): 1798-1809, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34348556

RESUMO

Identifying isoform-specific inhibitors for closely related kinase family members remains a substantial challenge. The necessity for achieving this specificity is exemplified by the RSK family, downstream effectors of ERK1/2, which have divergent physiological effects. The natural product, SL0101, a flavonoid glycoside, binds specifically to RSK1/2 through a binding pocket generated by an extensive conformational rearrangement within the RSK N-terminal kinase domain (NTKD). In modelling experiments a single amino acid that is divergent in RSK3/4 most likely prevents the required conformational rearrangement necessary for SL0101 binding. Kinetic analysis of RSK2 association with SL0101 and its derivatives identified that regions outside of the NTKD contribute to stable inhibitor binding. An analogue with an n-propyl-carbamate at the 4" position on the rhamnose moiety was identified that forms a highly stable inhibitor complex with RSK2 but not with RSK1. These results identify a SL0101 modification that will aid the identification of RSK2 specific inhibitors.


Assuntos
Benzopiranos/síntese química , Monossacarídeos/síntese química , Inibidores de Proteínas Quinases/síntese química , Proteínas Quinases S6 Ribossômicas 90-kDa/antagonistas & inibidores , Sequência de Aminoácidos , Benzopiranos/metabolismo , Carbamatos/química , Humanos , Cinética , Modelos Moleculares , Monossacarídeos/metabolismo , Ligação Proteica , Conformação Proteica , Inibidores de Proteínas Quinases/metabolismo , Ramnose/química , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Relação Estrutura-Atividade
8.
J Med Food ; 24(8): 852-859, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34382871

RESUMO

CYJ-27, a synthetic analog of decursin, prevents the generation of proinflammatory cytokines and oxidative stress. In this study, the effects of CYJ-27 on the regulation of inducible nitric oxide synthase (iNOS), heme oxygenase (HO)-1, and cyclooxygenase (COX-)2 were characterized in lipopolysaccharide (LPS)-treated human umbilical vein endothelial cells (HUVECs). In addition, the effects of CYJ-27 on the production of iNOS and representative proinflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1ß, were tested in the lung tissues of LPS-treated mice. CYJ-27 promoted the expression of HO-1, suppressed NF-κB-luciferase activity, and reduced COX-2/PGE2 and iNOS/NO, resulting in a diminution in phosphorylated-STAT-1. Furthermore, CYJ-27 promoted the nuclear translocation of Nrf2, enhanced the combination of Nrf2 to antioxidant response elements, and diminished IL-1ß production in LPS-activated HUVECs. CYJ-27-downregulated iNOS/NO expression was rescued after the RNAi suppression of HO-1. In LPS-treated mice, CYJ-27 significantly diminished iNOS production in the lung tissues and TNF-α expression in the bronchoalveolar lavage fluid. These findings indicate that CYJ-27 exerts anti-inflammatory activities by regulating iNOS through downregulation of both NF-κB activation and phosphorylated-STAT-1. Hence, it can act as a template for the development of novel substances to treat inflammatory diseases.


Assuntos
Inflamação , NF-kappa B , Animais , Benzopiranos , Butiratos , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/genética , Lipopolissacarídeos , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo
9.
Sci Total Environ ; 796: 148780, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34280625

RESUMO

Aquaculture plays a pivotal role in covering dietary animal protein demands and restocking endangered fish populations. However, high mortality takes place at the earliest life stages: prior and immediately after hatching. Improving growth and health parameters by immunostimulants is widely used in older fish, but rarely studied in larvae. Fulvic acids (FAs) are natural substances found in soil and water. Using zebrafish as a model organism, we evaluated the effects of exposure to a FA at concentrations ranging from 1 to 500 mg C/L (mg dissolved organic carbon per liter) on embryonic development. Furthermore, the concentration of reactive oxygen species (ROS) inside the larvae as well as the molecular mechanisms involved in growth, immune response, and antioxidative protection were determined at 5, 50, and 500 mg C/L. 20 to 200 mg C/L accelerated the hatching, which was mediated by increased expression of ifg-1, gh, and he1-α. Furthermore, lyz and mpx were significantly increased at 5 and 50 mg C/L. A concentration of 500 mg C/L induced genes involved in the protection against ROS (nrf-2, keap-1, cat, sod-1), increased the concentration of ROS inside the larvae and caused tissue damage and mortality. Interestingly, 50 mg C/L activated ROS protection as well (nrf-2, sod-2), while no increase of ROS was found in the larvae. Our results show, that FA at low to medium concentrations can increase the health of larvae, but becomes detrimental at higher concentrations.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Antioxidantes/metabolismo , Benzopiranos , Embrião não Mamífero/metabolismo , Imunidade Inata , Larva , Estresse Oxidativo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade
10.
Molecules ; 26(14)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34299576

RESUMO

The search for a safe and effective inhibitor of ferroptosis, a recently described cell death pathway, has attracted increasing interest from scientists. Two hydrolyzable tannins, chebulagic acid and chebulinic acid, were selected for the study. Their optimized conformations were calculated using computational chemistry at the B3LYP-D3(BJ)/6-31G and B3LYP-D3(BJ)/6-311 + G(d,p) levels. The results suggested that (1) chebulagic acid presented a chair conformation, while chebulinic acid presented a skew-boat conformation; (2) the formation of chebulagic acid requires 762.1729 kcal/mol more molecular energy than chebulinic acid; and (3) the 3,6-HHDP (hexahydroxydiphenoyl) moiety was shown to be in an (R)- absolute stereoconfiguration. Subsequently, the ferroptosis inhibition of both tannins was determined using a erastin-treated bone marrow-derived mesenchymal stem cells (bmMSCs) model and compared to that of ferrostatin-1 (Fer-1). The relative inhibitory levels decreased in the following order: Fer-1 > chebulagic acid > chebulinic acid, as also revealed by the in vitro antioxidant assays. The UHPLC-ESI-Q-TOF-MS analysis suggested that, when treated with 16-(2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinyloxy free radicals, Fer-1 generated dimeric products, whereas the two acids did not. In conclusion, two hydrolyzable tannins, chebulagic acid and chebulinic acid, can act as natural ferroptosis inhibitors. Their ferroptosis inhibition is mediated by regular antioxidant pathways (ROS scavenging and iron chelation), rather than the redox-based catalytic recycling pathway exhibited by Fer-1. Through antioxidant pathways, the HHDP moiety in chebulagic acid enables ferroptosis-inhibitory action of hydrolyzable tannins.


Assuntos
Benzopiranos/farmacologia , Ferroptose/efeitos dos fármacos , Glucosídeos/farmacologia , Taninos Hidrolisáveis/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Benzopiranos/química , Células Cultivadas , Glucosídeos/química , Taninos Hidrolisáveis/química , Células-Tronco Mesenquimais/citologia , Modelos Moleculares , Ratos Sprague-Dawley
11.
Biomolecules ; 11(7)2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209734

RESUMO

Meroterpenoids are secondary metabolites formed due to mixed biosynthetic pathways which are produced in part from a terpenoid co-substrate. These mixed biosynthetically hybrid compounds are widely produced by bacteria, algae, plants, and animals. Notably amazing chemical diversity is generated among meroterpenoids via a combination of terpenoid scaffolds with polyketides, alkaloids, phenols, and amino acids. This review deals with the isolation, chemical diversity, and biological effects of 452 new meroterpenoids reported from natural sources from January 2016 to December 2020. Most of the meroterpenoids possess antimicrobial, cytotoxic, antioxidant, anti-inflammatory, antiviral, enzyme inhibitory, and immunosupressive effects.


Assuntos
Terpenos/química , Terpenos/isolamento & purificação , Terpenos/metabolismo , Alcaloides , Animais , Antibacterianos/metabolismo , Anti-Infecciosos/metabolismo , Antineoplásicos/metabolismo , Antioxidantes/metabolismo , Bactérias/metabolismo , Benzopiranos , Benzoquinonas , Produtos Biológicos/química , Vias Biossintéticas , Fungos/metabolismo , Humanos , Metabolismo Secundário/fisiologia , Sesquiterpenos
12.
J Proteomics ; 247: 104337, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34298183

RESUMO

The aim of this work was to gain insight into the molecular mechanisms underlying the effect of fulvic acid on drought-exposed tea plants. We performed proteomic analysis of fulvic acid-treated tea leaves from the target plants using tandem mass tag quantitative labeling technology and compared the results with those of a previous transcriptomic analysis. We identified 48 and 611 differentially abundant proteins in the leaves of tea plants treated with fulvic acid compared with the control under mild and severe drought, respectively. Comparative analysis showed that, under severe drought, 55 genes had similar expression patterns at the transcriptome and proteome levels, such as PAL, GBE, GBSS and bAS. Bioinformatic analysis revealed that those genes were mainly related to the starch and sucrose metabolism, phenylpropanoid biosynthesis and triterpenoid biosynthesis. SIGNIFICANCE: This study broadens the understanding of the molecular mechanisms underlying the improved drought resistance seen in tea plants in the presence of fulvic acid and provides a basis for further research on the genomics of drought tolerance in these plants. In addition, these findings could be used to develop new guidance strategies for improved drought management systems in tea plantation.


Assuntos
Camellia sinensis , Secas , Benzopiranos , Camellia sinensis/metabolismo , Regulação da Expressão Gênica de Plantas , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteômica , Metabolismo Secundário , Amido , Sacarose , Chá , Transcriptoma
13.
Molecules ; 26(12)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205355

RESUMO

Rottlerin is a natural product consisting of chalcone and flavonoid scaffolds, both of which have previously shown quorum sensing (QS) inhibition in various bacteria. Therefore, the unique rottlerin scaffold highlights great potential in inhibiting the QS system of Pseudomonas aeruginosa. Rottlerin analogues were synthesised by modifications at its chalcone- and methylene-bridged acetophenone moieties. The synthesis of analogues was achieved using an established five-step synthetic strategy for chalcone derivatives and utilising the Mannich reaction at C6 of the chromene to construct morpholine analogues. Several pyranochromene chalcone derivatives were also generated using aldol conditions. All the synthetic rottlerin derivatives were screened for QS inhibition and growth inhibition against the related LasR QS system. The pyranochromene chalcone structures displayed high QS inhibitory activity with the most potent compounds, 8b and 8d, achieving QS inhibition of 49.4% and 40.6% and no effect on bacterial growth inhibition at 31 µM, respectively. Both compounds also displayed moderate biofilm inhibitory activity and reduced the production of pyocyanin.


Assuntos
Acetofenonas/farmacologia , Benzopiranos/farmacologia , Produtos Biológicos/farmacologia , Percepção de Quorum/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Flavonoides/farmacologia , Testes de Sensibilidade Microbiana/métodos , Pseudomonas aeruginosa/efeitos dos fármacos , Piocianina/farmacologia
14.
Int J Mol Sci ; 22(13)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34281274

RESUMO

It has been recognized that serotonin 2A receptor (5-HT2A) agonist 2,5-dimethoxy-4-iodo-amphetamine (DOI) impairs serotonergic homeostasis. However, the mechanism of DOI-induced serotonergic behaviors remains to be explored. Moreover, little is known about therapeutic interventions against serotonin syndrome, although evidence suggests that ginseng might possess modulating effects on the serotonin system. As ginsenoside Re (GRe) is well-known as a novel antioxidant in the nervous system, we investigated whether GRe modulates 5-HT2A receptor agonist DOI-induced serotonin impairments. We proposed that protein kinase Cδ (PKCδ) mediates serotonergic impairments. Treatment with GRe or 5-HT2A receptor antagonist MDL11939 significantly attenuated DOI-induced serotonergic behaviors (i.e., overall serotonergic syndrome behaviors, head twitch response, hyperthermia) by inhibiting mitochondrial translocation of PKCδ, reducing mitochondrial glutathione peroxidase activity, mitochondrial dysfunction, and mitochondrial oxidative stress in wild-type mice. These attenuations were in line with those observed upon PKCδ inhibition (i.e., pharmacologic inhibitor rottlerin or PKCδ knockout mice). Furthermore, GRe was not further implicated in attenuation mediated by PKCδ knockout in mice. Our results suggest that PKCδ is a therapeutic target for GRe against serotonergic behaviors induced by DOI.


Assuntos
Ginsenosídeos/farmacologia , Proteína Quinase C-delta/metabolismo , Antagonistas da Serotonina/farmacologia , Síndrome da Serotonina/prevenção & controle , Acetofenonas/farmacologia , Anfetaminas/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Benzopiranos/farmacologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Piperidinas/farmacologia , Proteína Quinase C-delta/deficiência , Proteína Quinase C-delta/genética , Inibidores de Proteínas Quinases/farmacologia , Serotonina/fisiologia , Agonistas do Receptor de Serotonina/farmacologia , Síndrome da Serotonina/induzido quimicamente , Síndrome da Serotonina/fisiopatologia
15.
Phytochemistry ; 190: 112851, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34217043

RESUMO

Fungal endophytes are remarkable sources of biologically active metabolites of ecological and pharmacological significance. In this study, fungal isolates producing yellow pigments and originating from grass roots, were identified as the recently described grass root colonizing dark septate endophyte (DSE), Flavomyces fulophazii (Periconiaceae, Pleosporales). While analyzing the metabolite composition of 17 isolates of this fungus, 11 previously undescribed compounds, including four tetramic acids (dihydroxyvermelhotin, hydroxyvermelhotin, methoxyvermelhotin, oxovermelhotin), and seven chlorinated azaphilones (flavochlorines A-G), together with the known tetramic acid vermelhotin, were tentatively identified by high performance liquid chromatography (HPLC)-tandem mass spectrometry (MS/MS). Among them, flavochlorine A, flavochlorine G, hydroxyvermelhotin and vermelhotin could be isolated by preparative HPLC, thus their structures were also confirmed by nuclear magnetic resonance (NMR) spectroscopy. Vermelhotin was found to be the main compound, reaching its maximum level of 5.5 mg/g in the in vitro cultures of a selected F. fulophazii isolate. A significant amount of vermelhotin was isolated by preparative HPLC from these cultures (4.8 mg from 1.0 g lyophilized culture), confirming the practical utility of F. fulophazii in high-yield vermelhotin production. The main compounds of this endophyte expressed no activity in standardized plant bioassays (i.e., in the Lactuca sativa seed germination and Lemna minor growth tests). An antiproliferative study of the isolated compounds confirmed moderate activity of vermelhotin against a panel of twelve cancer cell lines, with IC50 ranges of 10.1-37.0 µM, without inhibiting the non-cancer Vero cells, suggesting its selectivity towards cancers.


Assuntos
Ascomicetos , Espectrometria de Massas em Tandem , Animais , Benzopiranos , Chlorocebus aethiops , Endófitos , Pigmentos Biológicos , Pirrolidinonas , Células Vero
16.
Int J Mol Sci ; 22(14)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34299073

RESUMO

Theasinensin A (TSA) is a major group of catechin dimers mainly found in oolong tea and black tea. This compound is also manufactured with epigallocatechin gallate (EGCG) as a substrate and is refined after the enzyme reaction. In previous studies, TSA has been reported to be effective against inflammation. However, the effect of these substances on skin melanin formation remains unknown. In this study, we unraveled the role of TSA in melanogenesis using mouse melanoma B16F10 cells and normal human epidermal melanocytes (NHEMs) through reverse transcription polymerase chain reaction (RT-PCR), Western blotting analysis, luciferase reporter assay, and enzyme-linked immunosorbent assay analysis. TSA inhibited melanin formation and secretion in α-melanocyte stimulating hormone (α-MSH)-induced B16F10 cells and NHEMs. TSA down-regulated the mRNA expression of tyrosinase (Tyr), tyrosinase-related protein 1 (Tyrp1), and Tyrp2, which are all related to melanin formation in these cells. TSA was able to suppress the activities of certain proteins in the melanocortin 1 receptor (MC1R) signaling pathway associated with melanin synthesis in B16F10 cells: cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), protein kinase A (PKA), tyrosinase, and microphthalmia-associated transcription factor (MITF). We also confirmed α-MSH-mediated CREB activities through a luciferase reporter assay, and that the quantities of cAMP were reduced by TSA in the enzyme linked immunosorbent assay (ELISA) results. Based on these findings, TSA should be considered an effective inhibitor of hyperpigmentation.


Assuntos
Benzopiranos/farmacologia , AMP Cíclico/metabolismo , Melaninas/metabolismo , Melanócitos/efeitos dos fármacos , Melanoma Experimental/tratamento farmacológico , Fenóis/farmacologia , Animais , Humanos , Melanócitos/citologia , Melanócitos/metabolismo , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Fosforilação , Transdução de Sinais
17.
Bioresour Technol ; 337: 125495, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34320772

RESUMO

Here, we revealed the effects of microbes on fulvic acid (FA) formation in composting by adding MnO2. The results showed that the MnO2 promoted the formation of highly humified components (79.2% increased for component 2, and 45.8% increased for component 3) in FA. Additionally, core bacteria involved in FA transformation were identified, the MnO2 increased the relative abundance of core bacteria. Notably, two different core bacteria types were identified: "transforming bacteria" and "processing bacteria". The "transforming bacteria" dominated (about 40% contribution) in the formation of FA components with a high humification degree. The structural equation model confirmed that "transforming bacteria" could convert partly FA components with low humification into highly humified components, and the "transforming bacteria" could be regulated by environmental factors. These findings provided a new insight to manage FA humification degree during composting and helped to improve the application value of FA.


Assuntos
Compostagem , Bactérias/genética , Benzopiranos , Compostos de Manganês , Esterco , Óxidos , Solo
18.
Int J Mol Sci ; 22(12)2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34203049

RESUMO

The present study aims to determine the neuroprotective effect of Bergenin against spatial memory deficit associated with neurodegeneration. Preliminarily, the protective effect of Bergenin was observed against H2O2-induced oxidative stress in HT-22 and PC-12 cells. Further studies were performed in 5xFAD Tg mouse model by administering Bergenin (1, 30 and 60 mg/kg; orally), whereas Bergenin (60 mg/kg) significantly attenuated the memory deficit observed in the Y-maze and Morris water maze (MWM) test. Fourier transform-infrared (FT-IR) spectroscopy displayed restoration of lipids, proteins and their derivatives compared to the 5xFAD Tg mice group. The differential scanning calorimeter (DSC) suggested an absence of amyloid beta (Aß) aggregation in Bergenin-treated mice. The immunohistochemistry (IHC) analysis suggested the neuroprotective effect of Bergenin by increasing Reelin signaling (Reelin/Dab-1) and attenuated Aß (1-42) aggregation in hippocampal regions of mouse brains. Furthermore, IHC and western blot results suggested antioxidant (Keap-1/Nrf-2/HO-1), anti-inflammatory (TLR-4/NF-kB) and anti-apoptotic (Bcl-2/Bax/Caspase-3) effect of Bergenin. Moreover, a decrease in Annexin V/PI-stained hippocampal cells suggested its effect against neurodegeneration. The histopathological changes were reversed significantly by Bergenin. In addition, a remarkable increase in antioxidant level with suppression of pro-inflammatory cytokines, oxidative stress and nitric oxide production were observed in specific regions of the mouse brains.


Assuntos
Benzopiranos/farmacologia , Moléculas de Adesão Celular Neuronais/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Serina Endopeptidases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Benzopiranos/química , Biomarcadores , Linhagem Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Ligação de Hidrogênio , Mediadores da Inflamação/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/diagnóstico , Transtornos da Memória/tratamento farmacológico , Camundongos , Camundongos Transgênicos , Modelos Moleculares , Estrutura Molecular , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Relação Estrutura-Atividade , Resultado do Tratamento
19.
Molecules ; 26(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202485

RESUMO

In this work, steam explosion (SE) was exploited as a potential hydrothermal-humification process of vegetable wastes to deconstruct their structure and accelerate their decomposition to prepare humified substances. Results indicated that the SE process led to the removal of hemicellulose, re-condensation of lignin, degradation of the cellulosic amorphous region, and the enhancement of thermal stability of broccoli wastes, which provided transformable substrates and a thermal-acidic reaction environment for humification. After SE treatment, total humic substances (HS), humic acids (HAs), and fulvic acids (FAs) contents of broccoli samples accounted for up to 198.3 g/kg, 42.3 g/kg, and 166.6 g/kg, and their purification were also facilitated. With the increment of SE severity, structural characteristics of HAs presented the loss of aliphatic compounds, carbohydrates, and carboxylic acids and the enrichment of aromatic structures and N-containing groups. Lignin substructures were proved to be the predominant aromatic structures and gluconoxylans were the main carbohydrates associated with lignin in HAs, both of their signals were enhanced by SE. Above results suggested that SE could promote the decomposition of easily biodegradable matters and further polycondensation, aromatization, and nitrogen-fixation reactions during humification, which were conducive to the formation of HAs.


Assuntos
Benzopiranos/química , Substâncias Húmicas , Eliminação de Resíduos , Vapor , Verduras/química
20.
Molecules ; 26(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208750

RESUMO

Entamoeba histolytica (protozoan; family Endomoebidae) is the cause of amoebiasis, a disease related to high morbidity and mortality. Nowadays, this illness is considered a significant public health issue in developing countries. In addition, parasite resistance to conventional medicinal treatment has increased in recent years. Traditional medicine around the world represents a valuable source of alternative treatment for many parasite diseases. In a previous paper, we communicated about the antiprotozoal activity in vitro of the methanolic (MeOH) extract of Ruta chalepensis (Rutaceae) against E. histolytica. The plant is extensively employed in Mexican traditional medicine. The following workup of the MeOH extract of R. chalepensis afforded the furocoumarins rutamarin (1) and chalepin (2), which showed high antiprotozoal activity on Entamoeba histolytica trophozoites employing in vitro tests (IC50 values of 6.52 and 28.95 µg/mL, respectively). Therefore, we offer a full scientific report about the bioguided isolation and the amebicide activity of chalepin and rutamarin.


Assuntos
Furocumarinas/isolamento & purificação , Ruta/metabolismo , Amebicidas/isolamento & purificação , Amebicidas/farmacologia , Antiprotozoários/farmacologia , Benzopiranos/metabolismo , Entamoeba histolytica/efeitos dos fármacos , Entamoeba histolytica/patogenicidade , Furocumarinas/farmacologia , Concentração Inibidora 50 , Medicina Tradicional , México , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia
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