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1.
J Ethnopharmacol ; 282: 114607, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34506940

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Paeonia lactiflora is a traditionally-used whitening medicine in China for thousands of years. Although some tyrosinase inhibitors and/or antioxidants such as 1,2,3,4,6-pentagalloylglucose, gallic acid, have been isolated and identified, their tyrosinase inhibition pathway (monophenolase or diphenolase inhibition, or both two) have not been systematically studied and the underlying tyrosinase inhibition mechanism has not been revealed yet. Moreover, the exploring of new natural tyrosinase inhibitors and antioxidants is urgently needed. AIM OF THE STUDY: This review aimed to develop a new microplate-based high-resolution tyrosinase inhibition profiling assay and establish a furthermore triple high-resolution monophenolase/diphenolase/radical scavenging profiling for accelerating identification bioactive compounds from complicated plant extract. MATERIALS AND METHODS: The targeted isolation and structure elucidation were performed with high-performance liquid chromatography-high-resolution mass spectrometry and preparative high-performance liquid chromatography. It allows to be a proof of concept with the root of Paeonia lactiflora crude extract as a natural whitening herbal drug. RESULTS: The result showed that galloylpaeoniflorin specifically inhibited monophenolase activity. While 1,2,3,4,6-pentagalloylglucose, gallic acid and catechin demonstrated the inhibition towards both monophenolase and diphenolase. Among them, 1,2,3,4,6-pentagalloylglucose can inhibit monophenolase activity was reported for the first time. In addition, antioxidant properties were attributed to catechin, 1,2,3,4,6-pentagalloylglucose and gallic acid. Due to its low content and complicated configuration in the root of Paeonia lactiflora, a new potential tyrosinase inhibitor and radical scavenger which tentatively identified as hexagalloylglucose by high-resolution MS was still need further verification. What's more, the molecular docking unveiled that bioactive enzymatic inhibitors mainly interacted with amino acid catalytic residues of tyrosinase via H-bonds and van der wals, which may be helpful to understand their inhibition mechanisms with tyrosinase in the skin whitening. CONCLUSIONS: The platform provided a promising and efficient strategy for the rapid screening of whitening active components from natural sources.

2.
Phytochemistry ; 195: 113056, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34953266

RESUMO

Phytochemical investigation of Lycopodium cernuum L. afforded seven undescribed serratene triterpenoids named 3ß, 21ß-dihydroxyserra-14-en-24-oic acid-3ß-(5'-hydroxybenzoate) (1), 3ß, 21ß, 24-trihydroxyserrat-14-en-3ß-(5'-hydroxyl benzoate) (2), 3ß, 14α, 15α, 21ß-tetrahydroxyserratane-24-methyl ester (3), 3ß, 14α, 21ß-trihydroxyserratane-15α-(4'-methoxy-5'-hydroxybenzoate)-24-methyl ester (4), 3ß, 14α, 21ß-trihydroxyserratane-15α-(4'-methoxy-5'-hydroxybenzoate) (5), 3ß-hydroxy-21ß-acetate-16-oxoserrat-14-en-24-oic acid (6), 3ß, 21ß-dihydroxy-16α, 29-epoxyserrat-14-en-24-methyl ester (7), together with eleven known compounds (8-18), whose chemical structures were elucidated through spectroscopic analysis of HRESIMS, 1D NMR, 2D NMR and comparison between the literature. All compounds were evaluated for their α-glucosidase inhibitory activity for the first time. The results showed that compounds 1, 2, 4, 5, 6, 10, 13, 15, and 16 were among the most potent α-glucosidase inhibitors, with IC50 values ranging from 23.22 ± 0.64 to 50.65 ± 0.82 µM. Structure-activity relationship (SAR) studies indicated that the combined properties of the 5-hydroxybenzoate moiety at C-3, ß-OH at C-21, COOH- at C-24, and Δ14,15 groups enabled an increase in the α-glucosidase inhibitory effect. In addition, molecular docking studies showed that the potential inhibitors mainly interact with key amino acid residues in the active site of α-glucosidase through hydrogen bonds and hydrophobic forces.


Assuntos
Lycopodium , Triterpenos , Inibidores de Glicosídeo Hidrolases/farmacologia , Imidazóis , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonamidas , Tiofenos , Triterpenos/farmacologia
3.
Bioorg Chem ; 116: 105273, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34474304

RESUMO

The ubiquitin-specific protease 7 (USP7)-murine double minute 2 (MDM2)-p53 network plays an important role in the regulation of p53, a tumor suppressor which plays critical roles in regulating cell growth, proliferation, cell cycle progression, apoptosis and immune response. The overexpression of USP7 and MDM2 in human cancers contributes to cancer initiation and progression, and their inhibition reactivates p53 signalings and causes cell cycle arrest and apoptosis. Herein, the current state of pharmacological characterization, potential applications in cancer treatment and mechanism of action of small molecules used to target and inhibit MDM2 and USP7 proteins are highlighted, along with the outcomes in clinical and preclinical settings. Moreover, challenges and advantages of these strategies, as well as perspectives in USP7-MDM2-p53 field are analyzed in detail. The investigation and application of MDM2 and USP7 inhibitors will deepen our understanding of the function of USP7-MDM2-p53 network, and feed in the development of effective and safe cancer therapies where USP7-MDM2-p53 network is implicated.

4.
Adv Sci (Weinh) ; 8(14): e2100701, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34050638

RESUMO

Switchable wetting and optical properties on a surface is synergistically realized by mechanical or temperature stimulus. Unfortunately, in situ controllable wettability together with programmable transparency on 2D/3D surfaces is rarely explored. Herein, Joule-heat-responsive paraffin-impregnated slippery surface (JR-PISS) is reported by the incorporation of lubricant paraffin, superhydrophobic micropillar-arrayed elastomeric membrane, and embedded transparent silver nanowire thin-film heater. Owing to its good flexibility, in situ controllable locomotion for diverse liquids on planar/curved JR-PISS is unfolded by alternately applying/discharging low electric-trigger of 6 V. Simultaneously, optical visibility can be reversibly converted between opaque and transparent modes. The switching principle is that in the presence of Joule-heat, solid paraffin would be melt and swell within 20 s to enable a slippery surface for decreasing light scattering and frictional force derived from contact angle hysteresis (FCAH ). Once Joule-heat is discharged, undulating rough surface would reconfigure by cold-shrinkage of paraffin within 8 s to render light blockage and high FCAH . Upon its portable merit, in situ thermal management, programmable visibility, as well as steering functionalized droplets by electric-activated JR-PISSs are successfully deployed. Compared with previous Nepenthes-inspired slippery surfaces, the current JR-PISS is more competent for in situ harnessing optical and wetting properties on-demand.

5.
Drug Discov Today ; 26(2): 490-502, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33157193

RESUMO

Human ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that removes the ubiquitin (Ub) protein and spares substrates from degradation. Given its regulation of proteins involved in several cellular processes, abnormal expression and activity of USP7 are associated with several types of disease, including cancer. In this review, we summarize the developments in our understanding of USP7 over the past 5 years, focusing on its role in related cancers. Furthermore, we discuss clinical studies of USP7, including in vivo and pharmacological studies, as well as the development of USP7 inhibitors. A comprehensive understanding of USP7 will expand our knowledge of the structure and function of USP7-mediated signaling and shed light on drug discovery for different diseases in which USP7 is implicated.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32012967

RESUMO

The purpose of this paper is to analyze the characteristics and human effects of atmospheric pollution in the Yangtze River Basin (YRB). An AQI(Air Quality Index)-based weighted co-word method is applied to explore the characteristics of keywords taken from the data, using authoritative media sources and government reports. Hierarchical clustering techniques are utilized to classify and visualize the keywords and display the different types of incidents. The results reveal the following four main clusters: enterprise pollution, coal-burning pollution, traffic pollution, and air pollutants. Cluster 1 is divided into 7 sub-clusters to offer powerful insight into the structural characteristics of industrial activities. This study is one of the first attempts to use a bibliometric approach to visualize the underlying and interconnected sub-clusters from grey data. It also provides an atmospheric pollution mapping for formulating government policies by understanding the human effects of air pollution incidents.


Assuntos
Poluição do Ar/análise , Monitoramento Ambiental , Poluentes Atmosféricos/análise , China , Análise por Conglomerados , Indústrias
7.
Talanta ; 200: 279-287, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31036185

RESUMO

Plants are well-recognized sources of inhibitors for α-glucosidase - a key target enzyme for management of type 2 diabetes. Recently, two advanced bioactivity-profiling techniques, i.e., ligand fishing and high-resolution inhibition profiling, have shown great promises for accelerating identification of α-glucosidase inhibitors from complex plant extracts. Non-specific affinities and non-specific inhibitions are major sources of false positive hits from ligand fishing and high-resolution inhibition profiling, respectively. In an attempt to minimize such false positive hits, we describe a new screening approach based on ligand fishing and high-resolution inhibition profiling for detection of high-affinity ligands and assessment of inhibitory activity, respectively. The complementary nature of ligand fishing and high-resolution inhibition profiling was explored to identify α-glucosidase inhibitory ligands from a complex mixture, and proof-of-concept was demonstrated with crude ethyl acetate extract of Ginkgo biloba. In addition to magnetic beads with a 3-carbon aliphatic linker, α-glucosidase was immobilized on magnetic beads with a 21-carbon aliphatic linker; and the two different types of magnetic beads were compared for their hydrolytic activity and fishing efficiency.


Assuntos
Biflavonoides/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Extratos Vegetais/farmacologia , alfa-Glucosidases/metabolismo , Biflavonoides/química , Biflavonoides/isolamento & purificação , Avaliação Pré-Clínica de Medicamentos , Ginkgo biloba/química , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Ligantes , Fenômenos Magnéticos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Saccharomyces cerevisiae/enzimologia , Relação Estrutura-Atividade
8.
Angew Chem Int Ed Engl ; 55(23): 6725-9, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27125576

RESUMO

Highly active and stable electrocatalysts for hydrogen generation from neutral-pH water are highly desired, but very difficult to achieve. Herein we report a facile synthetic approach to cobalt nanocrystal assembled hollow nanoparticles (Co-HNP), which serve as an electrocatalyst for hydrogen generation from neutral-pH water. An electrode composed of Co-HNP on a carbon cloth (CC) produces cathodic current densities of 10 and 100 mA cm(-2) at overpotentials of -85 mV and -237 mV, respectively. The Co-HNP/CC electrode retains its high activity after 20 h hydrogen generation at a high current density of 150 mA cm(-2) , indicating the superior activity and stability of Co-HNP as electrocatalyst.

9.
Food Chem ; 203: 16-22, 2016 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-26948583

RESUMO

Crude chloroform, ethanol and acetone extracts of nineteen seaweed species were screened for their antioxidant and α-glucosidase inhibitory activity. Samples showing more than 60% α-glucosidase inhibitory activity, at a concentration of 1 mg/ml, were furthermore investigated using high-resolution α-glucosidase inhibition profiling combined with high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy (HR-bioassay/HPLC-HRMS-SPE-NMR). The results showed Ascophyllum nodosum and Fucus vesicolosus to be rich in antioxidants, equaling a Trolox equivalent antioxidant capacity of 135 and 108 mM Troloxmg(-1) extract, respectively. HR-bioassay/HPLC-HRMS-SPE-NMR showed the α-glucosidase inhibitory activity of A. nodosum, F. vesoculosus, Laminaria digitata, Laminaria japonica and Undaria pinnatifida to be caused by phlorotannins as well as fatty acids - with oleic acid, linoleic acid and eicosapentaenoic acid being the most potent with IC50 values of 0.069, 0.075 and 0.10 mM, respectively, and showing a mixed-type inhibition mode.


Assuntos
Antioxidantes/isolamento & purificação , Alimento Funcional , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Alga Marinha/química , alfa-Glucosidases/metabolismo , Benzotiazóis/química , Cromatografia Líquida de Alta Pressão/métodos , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas , Extratos Vegetais/química , Alga Marinha/classificação , Extração em Fase Sólida/métodos , Especificidade por Substrato , Ácidos Sulfônicos/química
10.
J Nat Prod ; 78(2): 294-300, 2015 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-25679337

RESUMO

The crude methanol extract of Pueraria lobata was investigated by dual high-resolution α-glucosidase inhibition and radical scavenging profiling combined with hyphenated HPLC-HRMS-SPE-NMR. Direct analysis of the crude extract without preceding purification was facilitated by combining chromatograms from two analytical-scale HPLC separations of 120 and 600 µg on-column, respectively. High-resolution α-glucosidase and radical scavenging profiles were obtained after microfractionation of the eluate in 96-well microplates. This allowed full bioactivity profiling of individual peaks in the HPLC chromatogram of the crude methanol extract. Subsequent HPLC-HRMS-SPE-NMR analysis allowed identification of 21 known compounds in addition to two new compounds, i.e., 3'-methoxydaidzein 8-C-[α-D-apiofuranosyl-(1→6)]-ß-D-glucopyranoside and 6″-O-malonyl-3'-methoxydaidzin, as well as an unstable compound tentatively identified as 3'-de-O-methylpuerariafuran.


Assuntos
Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/farmacologia , Isoflavonas/isolamento & purificação , Isoflavonas/farmacologia , Pueraria/química , alfa-Glucosidases/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Glucosídeos/química , Inibidores de Glicosídeo Hidrolases/química , Isoflavonas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Extratos Vegetais/química , Extração em Fase Sólida
11.
Fitoterapia ; 84: 54-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23103953

RESUMO

An alkaloid with novel skeleton, sinoscrewtine (1), has been isolated from the roots of Sinomenium acutum. Its structure was established by spectral analysis and X-ray crystallographic study, and its possible biosynthetic pathway was delivered. In vitro experiments, 1 showed weak injurious effects against H(2)O(2)/Aß(25-35) induced oxidative injury in PC-12 cells and DPPH radical scavenging activity with IC(50) of 32.6µM.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Raízes de Plantas/química , Sinomenium/química , Animais , Modelos Moleculares , Estrutura Molecular , Células PC12 , Ratos
12.
J Asian Nat Prod Res ; 13(6): 523-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21623515

RESUMO

Two new morphinane alkaloids, 1-hydroxy-10-oxo-sinomenine (1) and 4,5-epoxy-14-hydroxy sinomenine N-oxide (2), have been isolated from the stems of Sinomenium acutum. Their structures were established by various spectral analyses, especially 2D NMR experiments. The structure of 2 was confirmed by single crystal X-ray diffraction. The absolute configurations of 1 and 2 were deduced by comparison of CD spectra with the known alkaloid sinomenine (3). Compound 1 was tested for DPPH inhibition and gave IC(50) of 27.9 µM. Compound 2 was tested for neuroprotective effect and showed significant activity against ß-amyloid(25-35)-induced oxidative injury (*P < 0.05) at 10 µM in PC-12 cells.


Assuntos
Alcaloides/isolamento & purificação , Óxidos N-Cíclicos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Morfinanos/isolamento & purificação , Fármacos Neuroprotetores/isolamento & purificação , Alcaloides/química , Alcaloides/farmacologia , Animais , Compostos de Bifenilo/farmacocinética , Óxidos N-Cíclicos/química , Óxidos N-Cíclicos/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Estrutura Molecular , Morfinanos/química , Morfinanos/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Ressonância Magnética Nuclear Biomolecular , Células PC12 , Picratos/farmacocinética , Caules de Planta/química , Ratos , Sinomenium/química , Difração de Raios X
13.
Fitoterapia ; 82(6): 793-7, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21596111

RESUMO

Four new fluorenone alkaloids, caulophylline A-D (1-4), and one new dihydroazafluoranthene alkaloid, caulophylline E (5) were isolated from the roots of Caulophyllum robustum Maxim. Their structures were elucidated by spectroscopic analysis. Among the isolated alkaloids, Caulophylline E showed good scavenging effects against DPPH radical with IC(50) of 39 µM.


Assuntos
Alcaloides/isolamento & purificação , Caulophyllum/química , Fluorenos/química , Fluorenos/isolamento & purificação , Alcaloides/química , Alcaloides/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Dibenzazepinas/química , Dibenzazepinas/isolamento & purificação , Dibenzazepinas/farmacologia , Fluorenos/farmacologia , Concentração Inibidora 50 , Medicina Tradicional Chinesa , Estrutura Molecular , Picratos/antagonistas & inibidores , Raízes de Plantas/química
14.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 22(12): 1466-9, 2008 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-19137892

RESUMO

OBJECTIVE: To investigate the influence of diammonium glycyrrhizinate (DG) on the expression of NF-kappaB and neuron apoptosis after spinal cord ischemia-reperfusion injury in rats. METHODS: Fourty-eight healthy SD male rats, weighing 220-270 g, were randomly divided into the experimental group and the control group, with 24 rats in each group. A model of spinal cord ischemia-reperfusion injury was completed by intercepting the rats' abdominal aorta between right and left renal arteries for 30 minunts. In the experimental group, each rat was injected 20 mg/kg DG via sublingual vein 10 minutes before ischemia occurred. Equal qualities of physiological saline were injected into the rats in the control group. The two groups were observed at 3, 24, 72 and 168 hours after ischemia-reperfusion, respectively. Lumbar myeloid tissues were prepared at the different times, respectively. The expression of NF-kappaB p65 in lumbar myeloid tissues was analyzed by immunohistochemistry and the apoptosis of neurons was examined by TUNEL reaction. Meanwhile, histological changes of spinal cord were observed by HE staining. Then the correlation between NF-kappaB and neuron apoptosis was analyzed. RESULTS: HE staining showed obvious histological changes of spinal cord of the two groups. In the control group, myeloid tissue edema and normal neurons were observed at 3 hours; there were more histological changes at 24 hours and 72 hours; vacuoles in gray matters and some survived neurons were seen at 168 hours. The histological changes at each time in the experimental group were fewer than those in the control group. The immunohistochemical staining showed that the expression of NF-kappaB p65 was observed. After ischemia-reperfusion, the expression strengthened at 3 hours, reached the peak at 24 hours and then weakened slowly. At 3, 24, 72 and 168 hours after ischemia-reperfusion, the absorbency (A) value of NF-kappaB p65 in the experimental group was 0.306 0 +/- 0.024 4, 0.396 4 +/- 0.022 7, 0.296 6 +/- 0.021 1 and 0.267 9 +/- 0.015 3, respectively, and that in the control group was 0.361 1 +/- 0.017 7, 0.496 6 +/- 0.020 1, 0.356 3 +/- 0.0210 and 0.3014 +/- 0.018 1, respectively. There were significant differences between the two groups (P < 0.05). The inhabitation ratio of NF-kappaB p65 expression by DG was 15.40%, 20.17%, 19.28% and 11.11% at 3, 24, 72 and 168 hours after ischemia-reperfusion, respectively. Neuron apoptosis was observed, which strengthened at 3 hours and was the most serious at 24 and 168 hours after ischemia-reperfusion. At 3, 24, 72 and 168 hours after ischemia-reperfusion, the A value of neuron apoptosis in the experimental group was 0.1710 +/- 0.029 1, 0.175 5 +/- 0.0311, 0.175 1 +/- 0.027 9 and 0.183 2 +/- 0.023 7, respectively, and that in the control group was 0.236 8 +/- 0.063 6, 0.241 2 +/- 0.042 6, 0.201 5 +/- 0.049 8 and 0.250 1 +/- 0.048 4, respectively. There were significant differences between the two groups (P < 0.05). The inhabitation ratio of neuron apoptosis by DG was 27.79%, 27.23%, 13.08% and 26.74% at 3, 24, 72 and 168 hours after ischemia-reperfusion, respectively. The expression of NF-kappaB in myeloid tissues was positively correlated with neurons apoptosis in the two groups (r = 0.838, P < 0.01). CONCLUSION: Spinal cord ischemia-reperfusion injury may cause a marked expression of NF-kappaB and notable evidence of neurons apoptosis. DG can reduce neurons apoptosis by inhibiting the expression of NF-kappaB.


Assuntos
Apoptose , Ácido Glicirrízico/farmacologia , NF-kappa B/metabolismo , Traumatismo por Reperfusão/metabolismo , Isquemia do Cordão Espinal/metabolismo , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Medula Espinal/metabolismo
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