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1.
FASEB J ; 34(10): 13257-13271, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32860269

RESUMO

Fetal growth restriction (FGR) is a severe perinatal complication that can increase risk for mental illness. To investigate the mechanism by which FGR mice develop mental illness in adulthood, we established the FGR mouse model and the FGR mice did not display obvious depression-like behaviors, but after environmental stress exposure, FGR mice were more likely to exhibit depression-like behaviors than control mice. Moreover, FGR mice had significantly fewer dopaminergic neurons in the ventral tegmental area but no difference in serotoninergic neurons in the dorsal raphe. RNA-seq analysis showed that the downregulated genes in the midbrain of FGR mice were associated with many mental diseases and were especially involved in the regulation of NMDA-selective glutamate receptor (NMDAR) activity. Furthermore, the NMDAR antagonist memantine can relieve the stress-induced depression-like behaviors of FGR mice. In summary, our findings provide a theoretical basis for future research and treatment of FGR-related depression.

2.
Phytochemistry ; 178: 112461, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32692660

RESUMO

Eight pairs of enantiomeric lignans and neolignans including thirteen undescribed compounds, along with an undescribed meso compound, were isolated from the herbs of Solanum lyratum Thunb.(Solanaceae). Their structures and relative configurations were determined by extensive spectroscopic analyses of HRESIMS and nuclear magnetic resonance. The absolute configurations of the pure isomers were established based on the cooperative comparison between the experimental and calculated electronic circular dichroism (ECD) and optical rotation (OR). It is interesting that we obtained several naturally occurring stereoisomers with the identical gross structure possessing several stereogenic carbons from S. lyratum. Additionally, all isolates were assessed for neuroprotective effects toward human neuroblastoma SH-SY5Y cells injury induced by H2O2.


Assuntos
Lignanas , Fármacos Neuroprotetores , Solanum , Humanos , Peróxido de Hidrogênio , Estrutura Molecular
3.
J Asian Nat Prod Res ; : 1-6, 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32644854

RESUMO

Previous work has shown that the lignans from the twigs and leaves of Archidendron clypearia (Jack) I.C.N. possess anti-ß-amyloid aggregation activity. Here we report a new dilignan, archidendronin A (1), along with one known sesquilignan (2). Their structures were determined by extensive spectroscopic methods, including UV, HRESIMS, 1 D and 2 D NMR data. The inhibitory activity on Aß 1-42 aggregation was screened by ThT assay with curcumin as the positive control, and compounds 1 and 2 showed inhibition rate of 60.0% and 64.4% at 20 µM, respectively.

4.
Nat Prod Res ; : 1-8, 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32524840

RESUMO

Two triterpenes (14S,17S,20S,24R)-25-hydroxy-14,17-cyclo-20,24-epoxy-malabarican-3-one (CEM, 1a) and (14S,17S,20S,24R)-20,24,25-trihydroxy-14,17-cyclomalabarican-3-one (CM, 2a) with a cyclobutane ring were reported, which have the same NMR data as ocotillone (1b) and gardaubryone C (2b), respectively. An incorrect structure might be reported. Therefore, the structure reanalysis of these triterpenes was achieved by CASE algorithm and DFT chemical shift predictions, and the results showed that the structures of CEM and CM might be incorrect. To further verify the structure of compound 1, the HMBC, 1H-1H COSY and HSQC-TOCSY spectra were employed. Herein, we revised the structure of CEM and CM, and our study also showed that CASE algorithm and DFT chemical shift predictions can hold the post of effective structure reassignment method.

5.
Phytochemistry ; 176: 112414, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32446133

RESUMO

Five undescribed phenolics named pithecellobiumin C-G, along with thirteen known ones were isolated from the twigs and leaves of Archidendron clypearia (Jack) I.C.Nielsen. Their structures were elucidated based on comprehensive spectroscopic analyses, combined with computer-assisted structure elucidation software (ACD/Structure Elucidator) and gauge-independent atomic orbitals (GIAO) NMR chemical shift calculations. The absolute configurations were determined by comparison of experimental and calculated specific rotation and ECD curves. These compounds were tested for their neuroprotective activities against H2O2-induced injury in human neuroblastoma SH-SY5Y cells by MTT assay. Pithecellobiumin C-E exhibited noticeable neuroprotective effect. Further pharmacological study demonstrated that they could prevent cell death through inhibiting the apoptosis induction. Flow cytometry assays also proved that these compounds could attenuate reactive oxygen species (ROS) level and mitochondrial dysfunction in SH-SY5Y cells.


Assuntos
Fabaceae , Fármacos Neuroprotetores/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio
6.
Phytochemistry ; 175: 112361, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32289598

RESUMO

Seven undescribed terpenylated coumarins, named altissimacoumarin I-O, together with seven known compounds, altissimacoumarin C, altissimacoumarin E, altissimacoumarin G, altissimacoumarin H, puberulin, 7-(3-Methyl-2-butenyloxy)-6-methoxycoumarin and artelin were isolated from the root bark of Ailanthus altissima (Mill.) Swingle. Their structures were elucidated by comprehensive spectra data analysis, NMR calculation, DP4+ analysis and ACD/Structure Elucidator software simulation. The absolute configurations of altissimacoumarins K, L, M and N were determined by modified Mosher's method. All isolates were tested for their cytotoxic effect against two hepatoma carcinoma cell lines (HepG2, Hep3B). Altissimacoumarin C exhibited moderate cytotoxic effect against Hep3B cells, with IC50 of 45.21 µM.


Assuntos
Ailanthus , Cumarínicos , Casca de Planta , Extratos Vegetais
7.
J Am Chem Soc ; 142(7): 3506-3512, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-31986016

RESUMO

A highly efficient di-C-glycosyltransferase GgCGT was discovered from the medicinal plant Glycyrrhiza glabra. GgCGT catalyzes a two-step di-C-glycosylation of flopropione-containing substrates with conversion rates of >98%. To elucidate the catalytic mechanisms of GgCGT, we solved its crystal structures in complex with UDP-Glc, UDP-Gal, UDP/phloretin, and UDP/nothofagin, respectively. Structural analysis revealed that the sugar donor selectivity was controlled by the hydrogen-bond interactions of sugar hydroxyl groups with D390 and other key residues. The di-C-glycosylation capability of GgCGT was attributed to a spacious substrate-binding tunnel, and the G389K mutation could switch di- to mono-C-glycosylation. GgCGT is the first di-C-glycosyltransferase with a crystal structure, and the first C-glycosyltransferase with a complex structure containing a sugar acceptor. This work could benefit the development of efficient biocatalysts to synthesize C-glycosides with medicinal potential.


Assuntos
Glicosiltransferases/química , Glicosiltransferases/metabolismo , Glycyrrhiza/enzimologia , Clonagem Molecular , Cristalografia por Raios X , Glicosilação , Glicosiltransferases/genética , Glycyrrhiza/genética , Ligantes , Modelos Moleculares , Floretina/química , Floretina/metabolismo , Especificidade por Substrato , Transcriptoma , Uridina Difosfato Galactose/química , Uridina Difosfato Galactose/metabolismo , Uridina Difosfato Ácido Glucurônico/química , Uridina Difosfato Ácido Glucurônico/metabolismo , Uridina Difosfato N-Acetilglicosamina/química , Uridina Difosfato N-Acetilglicosamina/metabolismo , Uridina Difosfato Xilose/química , Uridina Difosfato Xilose/metabolismo
8.
Nat Prod Res ; 34(4): 456-463, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30445834

RESUMO

The phytochemical investigation on the twigs and leaves of Archidendron clypearia (Jack) I.C.N. led to the isolation of three pairs of furolactone-type lignans enantiomers, including a pair of new compounds (1R,5S,6S)-Kachiranol (1a) and (1S,5R,6R)-Kachiranol (1b) and four known compounds (2a/2b and 3a/3b). Separation of the furolactone-type lignans enantiomeric mixtures was achieved using chiral HPLC for the first time. Their structures were determined by spectroscopic analysis and comparison between the experimental and calculated electronic circular dichroism (ECD) spectra. All optical pure compounds were evaluated for their inhibitory effects on ß-amyloid aggregation by ThT assay. Among them, the inhibitory activity of the compound 1b (71.1%) was higher than the positive control (61.0%) and other compounds. In addition, molecular dynamics and molecular docking were employed to explore the binding relationship between the ligand and the receptor.


Assuntos
Fabaceae/química , Lignanas/química , Compostos Fitoquímicos/análise , Agregação Patológica de Proteínas/tratamento farmacológico , Peptídeos beta-Amiloides/efeitos dos fármacos , Dicroísmo Circular , Lignanas/isolamento & purificação , Lignanas/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Agregação Patológica de Proteínas/prevenção & controle , Estereoisomerismo
9.
Nat Prod Res ; 34(15): 2225-2228, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30821512

RESUMO

Enantiomers have generally been reported mostly for racemic mixtures with a 1:1 ratio, as in that case there were weak Cotton effects in the ECD spectrum and negligible optical rotations. A furofuran lignan (sesamin), with a remarkable rotation and significant Cotton effects, was isolated from Juglans mandshurica Maxim. Subsequently, sesamin was resolved by chiral HPLC to afford a pair of enantiomers, (+)-sesamin (a) and (-)-sesamin (b), in a ratio of approximately 1:3. Their absolute configurations were determined by computational analysis of their electronic circular dichroism (ECD) spectrum. In addition, the pair of enantiomers were evaluated for the inhibition of self-induced Aß aggregation. Interestingly, (+)-sesamin (a) (67.7%) and (-)-sesamin (b) (80.6%) exhibited different degrees of anti-Aß aggregation activity. The different inhibition profiles were further explained by molecular dynamics and docking simulation study.


Assuntos
Dioxóis/química , Furanos/isolamento & purificação , Juglans/química , Lignanas/isolamento & purificação , Rotação Ocular , Peptídeos beta-Amiloides/metabolismo , Juglans/efeitos dos fármacos , Lignanas/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Fragmentos de Peptídeos/metabolismo , Estereoisomerismo
10.
Cell Signal ; 66: 109465, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31698037

RESUMO

This study aimed to evaluate the correlation of integrin alpha 7 (ITGA7) with clinical outcomes and its effect on cell activities as well as stemness in hepatocellular carcinoma (HCC). HCC tumor tissues and paired adjacent tissues from 90 HCC patients were obtained and ITGA7 expression was detected using immunohistochemistry assay. Cellular experiments were conducted to examine the effect of ITGA7 on cell activities, astemness via ITGA7 ShRNA transfection, and compensation experiments were further performed to test whether ITGA7 functioned via regulating PTK2-PI3K-AKT signaling pathway. ITGA7 was overexpressed in tumor tissues compared with paired adjacent tissues and its high expression was correlated with larger tumor size, vein invasion and advanced Barcelona Clinic Liver Cancer stage, and it also independently predicted worse overall survival in HCC patients. In cellular experiments, ITGA7 was upregulated in SMMC-7721, Hep G2, HuH-7 and BEL-7404 cell lines compared with normal human liver cells HL-7702. ITGA7 knockdown suppressed cell proliferation but promoted apoptosis, and it also downregulated CSCs markers (CD44, CD133 and OCT-4) as well as PTK2, PI3K and AKT expressions in SMMC-7721 and Hep G2 cell lines. ITGA7 overexpression promoted cell proliferation but inhibited apoptosis, and it also upregulated CSCs markers in HL-7702 cells. Further compensation experiments verified that ITGA7 regulated cell proliferation, apoptosis and CSCs markers via PTK2-PI3K-Akt signaling pathway. ITGA7 negatively associates with clinical outcomes in HCC patients, and it regulates cell proliferation, apoptosis and CSCs markers via PTK2-PI3K-Akt signaling pathway.

11.
Fitoterapia ; 141: 104448, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31816344

RESUMO

Five undescribed macrocarpene-type sesquiterpenes (1-5), along with a known analogue (6) were isolated from the crude extract of stigma maydis. The structures of these compounds were elucidated based on comprehensive spectroscopic analyses together with quantum chemical calculations of 13C NMR data and electronic circular dichroism (ECD) curves. All isolated compounds were tested for their neuroprotective effects against the injury of human neuroblastoma SH-SY5Y cells induced by H2O2. Among them, compounds 3 (65.89%) and 5 (64.38%) showed moderate neuroprotective activity at 50 µM.


Assuntos
Flores/química , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Zea mays/química , Linhagem Celular Tumoral , China , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Peróxido de Hidrogênio , Estrutura Molecular , Neuroblastoma/tratamento farmacológico , Fármacos Neuroprotetores/química , Extratos Vegetais/química , Sesquiterpenos/química
12.
Langmuir ; 36(3): 789-795, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31815486

RESUMO

We report a facile yet general in situ seed-mediated method for the synthesis of polymer-grafted gold nanoparticles with narrow size distributions (<10%), accurately tunable sizes, and excellent colloidal stability. This method can be extended to a broad range of types and molecular weights of polymer ligands. Nanoparticles with different shapes can also be prepared by using preformed shaped nanoparticles directly as the seeds.

14.
J Asian Nat Prod Res ; : 1-6, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793831

RESUMO

Two new guaiane sesquiterpenes, 7-(1-hydroxyethyl)-4-methyl-1-azulenecarboxaldehyde (1) and 7-isopropenyl-4-methyl-1-azulenecarboxylic acid (2), together with 5 known sesquiterpenes, were isolated from the fruiting bodies of Lactarius deliciosus. All structures were elucidated based on extensive spectroscopic methods, including 1 D and 2 D-NMR spectroscopy and high resolution mass spectrometry.

15.
Nat Prod Res ; : 1-4, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31533476

RESUMO

A new triterpene as well as five known compounds were isolated from the twigs and leaves of Archidendron clypearia (Jack) I.C.N. Their structures were established by comprehensive spectroscopic analyses including 1D, 2D NMR and HRESIMS data. The ability of all isolated compounds to inhibit ß-amyloid aggregation was investigated by a ThT-based fluorometric assay. Among them, compounds 3 (67.8%) and 6 (77.7%) exhibited higher inhibitory activity than the positive (48.0%). In addition, molecular dynamics and molecular docking have been utilized to predict the detailed binding interaction between ligands and Aß1-42.

16.
Br J Pharmacol ; 176(17): 3126-3142, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31077347

RESUMO

BACKGROUND AND PURPOSE: Spermidine, a natural polyamine, is abundant in mammalian cells and is involved in cell growth, proliferation, and regeneration. Recently, oral spermidine supplements were cardioprotective in age-related cardiac dysfunction, through enhancing autophagic flux. However, the effect of spermidine on myocardial injury and cardiac dysfunction following myocardial infarction (MI) remains unknown. EXPERIMENTAL APPROACH: We determined the effects of spermidine in a model of MI, Sprague-Dawley rats with permanent ligation of the left anterior descending artery, and in cultured neonatal rat cardiomyocytes (NRCs) exposed to angiotensin II (Ang II). Cardiac function in vivo was assessed with echocardiography. In vivo and in vitro studies used histological and immunohistochemical techniques, along with western blots. KEY RESULTS: Spermidine improved cardiomyocyte viability and decreased cell necrosis in NRCs treated with angiotensin II. In rats post-MI, spermidine reduced infarct size, improved cardiac function, and attenuated myocardial hypertrophy. Spermidine also suppressed the oxidative damage and inflammatory cytokines induced by MI. Moreover, spermidine enhanced autophagic flux and decreased apoptosis both in vitro and in vivo. The protective effects of spermidine on cardiomyocyte apoptosis and cardiac dysfunction were abolished by the autophagy inhibitor chloroquine, indicating that spermidine exerted cardioprotective effects at least partly through promoting autophagic flux, by activating the AMPK/mTOR signalling pathway. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that spermidine improved MI-induced cardiac dysfunction by promoting AMPK/mTOR-mediated autophagic flux.


Assuntos
Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Cardiotônicos/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Espermidina/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/metabolismo , Angiotensina II/farmacologia , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Masculino , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Serina-Treonina Quinases TOR/metabolismo
17.
Nat Prod Res ; 33(16): 2368-2371, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29451024

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with synaptic dysfunction, pathological accumulation of ß-amyloid (Aß), and neuronal loss. Given the prevalence of AD and the lack of effective long-term therapies, there is a pressing need to discover viable leads that can be developed into clinically approved drugs with disease-modifying effects. The analysis of current reported literatures confirms the importance of the plants of Pithecellobium genus as candidate against AD. Hence, it is necessary to identify selective anti-dementia agents from this genus. To explore potential compounds with marked effect on AD in Pithecellobium genus, a compound database based on the methods of network pharmacology prediction was established in this paper by constructing the compound-disease target network. The result showed that the most effective compound in the plants of this genus might be (7'R,8'R)-7'-methoxyl strebluslignanol, and the most potential target might be Macrophage colony-stimulating factor 1 receptor.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos/métodos , Fabaceae/química , Nootrópicos/isolamento & purificação , Peptídeos beta-Amiloides/análise , Peptídeos beta-Amiloides/efeitos dos fármacos , Descoberta de Drogas/métodos , Humanos , Nootrópicos/farmacologia , Extratos Vegetais/química , Receptor de Fator Estimulador de Colônias de Macrófagos/antagonistas & inibidores
18.
Fitoterapia ; 132: 68-74, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30496811

RESUMO

Nine new prenylated flavan compounds with multi-chiral centers including two pairs of epimers were isolated from the stem and root bark of Daphne giraldii. Their structures were established by extensive NMR and HR-ESIMS spectroscopic data analyses. The in vitro cytotoxicity experiments indicated that compound 6 showed the most significant cytotoxicity against Hep3B cells, with an IC50 value of 9.83 µM. Hoechst 33258 and Annexin V-FITC/PI staining suggested that 6 could induce apoptosis of Hep3B cells in a concentration-dependent manner. Further mechanism study indicated that the apoptosis was associated with the up-regulations of Bax, cl-PARP and a decrease in Bcl-2 expression.


Assuntos
Antineoplásicos Fitogênicos/química , Daphne/química , Polifenóis/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose , Linhagem Celular Tumoral , China , Humanos , Estrutura Molecular , Casca de Planta/química , Caules de Planta/química , Poli(ADP-Ribose) Polimerases/metabolismo , Polifenóis/isolamento & purificação , Prenilação , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Regulação para Cima , Proteína X Associada a bcl-2/metabolismo
20.
Bioorg Chem ; 77: 579-585, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29477125

RESUMO

To develop potential agents for slowing the progression of Alzheimer's disease, two pairs of new enantiomeric lignans, including a couple of rarely 8',9'-dinor-3',7-epoxy-8,4'-oxyneolignanes named (7S, 8S)- and (7R, 8R)-pithecellobiumin A (1a/1b) and a pair of 2',9'-epoxy-arylnaphthalenes named (7R, 8R, 8'R)- and (7S, 8S, 8'S)-pithecellobiumin B (2a/2b) were separated by chiral high performance liquid chromatography (HPLC). Their planar structures were elucidated by spectroscopic data analyses. The absolute configurations were determined by comparing of experimental and calculated electronic circular dichroism (ECD). The inhibitory activity on Aß aggregation of all optical pure compounds was tested by ThT assay. Interestingly, enantiomeric inhibitors 1a (62.1%) and 1b (81.6%) exhibited different degrees of anti-Aß aggregation activity. However, 2a (65.4%) and 2b (68.4%) showed similar inhibition rate. The different inhibition profiles were explained by molecular dynamics and docking simulation studies.


Assuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Fabaceae/química , Lignanas/farmacologia , Peptídeos beta-Amiloides/metabolismo , Benzotiazóis/química , Relação Dose-Resposta a Droga , Corantes Fluorescentes/química , Humanos , Lignanas/química , Lignanas/isolamento & purificação , Modelos Moleculares , Estrutura Molecular , Folhas de Planta/química , Caules de Planta/química , Agregados Proteicos/efeitos dos fármacos , Estereoisomerismo , Relação Estrutura-Atividade
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