RESUMO
Traditional Chinese medicine has been utilized in China for approximately thousands of years in clinical settings to prevent Alzheimer's disease (AD) and enhance memory, despite the lack of a systematic exploration of its biological underpinnings. Exciting research has corroborated the beneficial effects of tetrahydroxy stilbene glycoside (TSG), an extract derived from Polygonum multiflorum, in delaying learning and memory impairment in a model that mimics AD. Therefore, the primary objective of this study is to investigate the major function of TSG upon protein regulation in AD. Herein, a novel approach, encompassing data independent acquisition (DIA), DIA phosphorylated proteomics, and parallel reaction monitoring (PRM), was utilized to integrate quantitative proteomic data collected from APP/PS1 mouse model exhibiting toxic intracellular aggregation of Aß. Initially, we deliberated upon both single and multi-dimensional data pertaining to AD model mice. Furthermore, we authenticated disparities in protein phosphorylation quantity and expression, phosphorylation function, and ultimately phosphorylation kinase analysis. In order to validate the results, we utilized PRM ion monitoring technology to identify potential protein or peptide biomarkers. In the mixed samples, targeted detection of 50 target proteins revealed that 26 to 33 target proteins were stably detected by PRM. In summary, our findings provide new candidates for AD biomarker, which have been identified and validated through protein researches conducted on mouse brains. This offers a wealth of potential resources for extensive biomarker validation in neurodegenerative diseases. SIGNIFICANCE: DIA phosphorylated proteomics technique was used to detect and analyze phosphorylated proteins in brain tissues of mice with AD. Data were analyzed by various bioinformatics tools to explore the phosphorylation events and characterize them related to TSG. The results of DIA were further verified by PRM. Besides, we mapped the major metabolite classes emerging from the analyses to key biological pathways implicated in AD to understand the potential roles of the molecules and the interactions in triggering symptom onset and progression of AD. Meanwhile, we clarified that in the context of AD onset and TSG intervention, the changes in proteins, protein phosphorylation, phosphorylation kinases, and the internal connections.
Assuntos
Doença de Alzheimer , Camundongos , Animais , Doença de Alzheimer/metabolismo , Proteômica , Precursor de Proteína beta-Amiloide , Glicosídeos , Biomarcadores , Camundongos Transgênicos , Modelos Animais de Doenças , Peptídeos beta-Amiloides/metabolismoRESUMO
Polygonum multiflorum Thunb. is a traditional Chinese medicine with extensive distribution and robust adaptability, but comprehensive research on its acid and alkali resistance is presently lacking. This study aimed to analyze the effects of 5 months of continuous pH stress on the physiological and photosynthetic parameters of P. multiflorum, and the content of effective components. Results revealed that pH stress significantly influenced the normal growth, physiological functions, and photosynthetic indicators of P. multiflorum. At soil pH 4.5, the tubers of P. multiflorum exhibited the highest levels of 2,3,5,4'-tetrahydroxy stilbene-2-O-ß-d-glucoside (THSG) and total anthraquinones at 5.41% and 0.38%, respectively. However, increased soil pH significantly reduced the content of THSG and total anthraquinones. Reference-free transcriptome analysis was further conducted on P. multiflorum treated at pH 4.5 and 9.5, generating a total of 47,305 unigenes with an N50 of 2118 bp, of which 31,058 (65.65%) were annotated. Additionally, 2472 differentially expressed genes (DEGs) were identified. Among them, 17 DEGs associated with the biosynthesis of THSG and anthraquinones were screened. A comprehensive analysis of differential gene expression and effective component content demonstrated a significant positive correlation between the content of effective components and the 14 DEGs' expression but a negative correlation with soil pH. This study highlighted the influence of varying soil pH values on the effective component content of P. multiflorum. Specific acidic conditions proved beneficial for the synthesis and accumulation of THSG and total anthraquinones in P. multiflorum, thereby enhancing the quality of the medicinal material.
Assuntos
Fallopia multiflora , Estilbenos , Fallopia multiflora/genética , Fallopia multiflora/química , Antraquinonas/análise , Tubérculos/química , Solo , Concentração de Íons de HidrogênioRESUMO
Cannabis sativa is a plant used for recreational and therapeutic purposes; however, many of the secondary metabolites in the plant have not been thoroughly investigated. Stilbenes are a class of compounds with demonstrated anti-inflammatory and antioxidant properties and are present in cannabis. Many stilbenes present in cannabis have been investigated for their therapeutic effects. Fourteen stilbenes have been identified to be present in cannabis, all of which are structurally dihydrostilbenoids, with half possessing a prenylated moiety. The stilbenes summarized in this analysis show varying degrees of therapeutic benefits ranging from anti-inflammatory, antiviral, and anti-cancer to antioxidant effects. Many of the identified stilbenes have been researched to a limited extent for potential health benefits. In addition, predictive in silico modeling was performed on the fourteen identified cannabis-derived stilbenes. This modeling provides prospective activity, pharmacokinetic, metabolism, and permeability data, setting the groundwork for further investigation into these poorly characterized compounds.
RESUMO
In present study, five series of 45 nitrogenous stilbenes including 35 new compounds were designed, synthesized, and assayed for cytotoxic activities against two human tumor cell lines (K562 cells and MDA-MB-231 cells) and normal cell line (L-02 cells). Structure-activity relationships showed the introduction of N,N-dimethylamino enhanced the cytotoxicities toward K562 cells and compounds with N-methyl piperazine displayed stronger potency toward MDA-MB-231 cells. Among them, compound NS1i possessed extremely potent cytotoxicity with IC50 values 0.93 µM against K562 cells along with excellent selectivity on normal cell viability. Moreover, in silico target prediction and molecule docking demonstrated quinone reductase 2 may be the potential target for NS1i. In summary, nitrogenous stilbenes afford significant potential for the discovery of new highly efficient anticancer agents and NS1i may serve as a promising lead deserve further investigation.
Assuntos
Antineoplásicos , Estilbenos , Humanos , Estrutura Molecular , Estilbenos/farmacologia , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/farmacologia , Relação Estrutura-Atividade , Linhagem Celular Tumoral , Desenho de Fármacos , Simulação de Acoplamento MolecularRESUMO
Malonyl-CoA is a central precursor for biosynthesis of a wide range of complex secondary metabolites. The development of platform strains with increased malonyl-CoA supply can contribute to the efficient production of secondary metabolites, especially if such strains exhibit high tolerance towards these chemicals. In this study, Pseudomonas taiwanensis VLB120 was engineered for increased malonyl-CoA availability to produce bacterial and plant-derived polyketides. A multi-target metabolic engineering strategy focusing on decreasing the malonyl-CoA drain and increasing malonyl-CoA precursor availability, led to an increased production of various malonyl-CoA-derived products, including pinosylvin, resveratrol and flaviolin. The production of flaviolin, a molecule deriving from five malonyl-CoA molecules, was doubled compared to the parental strain by this malonyl-CoA increasing strategy. Additionally, the engineered platform strain enabled production of up to 84 mg L-1 resveratrol from supplemented p-coumarate. One key finding of this study was that acetyl-CoA carboxylase overexpression majorly contributed to an increased malonyl-CoA availability for polyketide production in dependence on the used strain-background and whether downstream fatty acid synthesis was impaired, reflecting its complexity in metabolism. Hence, malonyl-CoA availability is primarily determined by competition of the production pathway with downstream fatty acid synthesis, while supply reactions are of secondary importance for compounds that derive directly from malonyl-CoA in Pseudomonas.
Assuntos
Malonil Coenzima A , Policetídeos , Pseudomonas , Ácidos Graxos/metabolismo , Malonil Coenzima A/metabolismo , Policetídeos/metabolismo , Pseudomonas/classificação , Pseudomonas/genética , Pseudomonas/metabolismo , Resveratrol/metabolismo , Metabolismo Secundário , Estilbenos/metabolismo , Ácidos Cumáricos/metabolismo , Fenilalanina/metabolismo , Genoma Bacteriano/genética , Deleção de Sequência , Acetilcoenzima A/metabolismo , Citrato (si)-Sintase/metabolismo , Ácido Pirúvico/metabolismo , Fitoalexinas/metabolismo , Naftoquinonas/metabolismoRESUMO
In present study, three series of 2,6-dihalogenated stilbene derivatives were designed, synthesized, and assayed for anti-inflammatory and cytotoxic activities. All 62 compounds showed potential anti-inflammatory activity in zebrafish model in vivo, and the installation of halogens and pyridines led to significant improved effects. Among them, DHS2u and DHS3u with the substitution of pyridine showed more higher effects than positive drug indomethacin at 20 µM with inhibitory rate of 94.59% and 90.54%, respectively. Besides, DHS3g bearing 2,5-dimethoxy exhibited potent cytotoxic activity against K562 cells with IC50 values 3.12 µM along with a suitable selectivity on normal cell viability. These results showed that 2,6-dihalogenated stilbenes could serve as a bright starting point for the further development as anti-inflammatory and antitumor agents.
Assuntos
Antineoplásicos , Estilbenos , Animais , Estrutura Molecular , Relação Estrutura-Atividade , Estilbenos/farmacologia , Peixe-Zebra , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/farmacologia , Anti-Inflamatórios/farmacologia , Desenho de Fármacos , Proliferação de CélulasRESUMO
BACKGROUND: The resistance of Gram-negative bacteria to polymyxin B, caused by the plasmid-mediated colistin resistance gene mcr-1, which encodes a phosphoethanolamine transferase (MCR-1), is a serious threat to global public health. Therefore, it is urgent to find new drugs that can effectively alleviate polymyxin B resistance. Through the screening of 78 natural compounds, we found that cajanin stilbene acid (CSA) can significantly restore the susceptibility of polymyxin B to mcr-1 positive Escherichia coli (E. coli). PURPOSE: In this study, we tried to evaluate the ability of CSA to restore the susceptibility of polymyxin B towards the E. coli, and explore the mechanism of sensitivity recovery. STUDY DESIGN AND METHODS: Checkerboard MICs, time-killing curves, scanning electron microscope, lethal and semi-lethal models of infection in mice were used to assess the ability of CSA to restore the susceptibility of polymyxyn to E. coli. The interaction between CSA and MCR-1 was evaluated using surface plasmon resonance (SPR), and molecular docking experiments. RESULTS: Here, we find that CSA, a potential direct inhibitor of MCR-1, effectively restores the sensitivity of E. coli to polymyxin B. CSA can restore the sensitivity of polymyxin B to drug-resistant E. coli, and the MIC value can be reduced to 1 µg/ml. The time killing curve and scanning electron microscopy results also showed that CSA can effectively restore polymyxin B sensitivity. In vivo experiments showed that the simultaneous use of CSA and polymyxin B can effectively reduce the infection of drug-resistant E. coli in mice. SPR and molecular docking experiments confirmed that CSA strongly bound to MCR-1. The 17-carbonyl oxygen and 12- and 18hydroxyl oxygens of CSA were the key sites binding to MCR-1. CONCLUSION: CSA is able to significantly restore the sensitivity of polymyxin B to E. coli in vivo and in vitro. CSA inhibits the enzymatic activity of the MCR-1 protein by binding to key amino acids at the active center of the MCR-1 protein.
Assuntos
Colistina , Proteínas de Escherichia coli , Animais , Camundongos , Colistina/farmacologia , Polimixina B/farmacologia , Antibacterianos/farmacologia , Escherichia coli , Simulação de Acoplamento Molecular , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/farmacologia , PlasmídeosRESUMO
One new compound, 4,7-dihydroxy-2-hydroxymethyl-5,6-dimethoxyanthraquinone (1), along with eight known compounds (2-9) were isolated from the methanol extracts of the aerial parts of Chamaecrista pumila (Lam.) K. Larsen. Their chemical structure was determined based on spectroscopic data interpretation and comparison with the reported data. The inhibitory effects of them on α-amylase and α-glucosidase were performed. The results showed that compounds 4, 6, 8, and 9 against potent α-glucosidase with the inhibition values of 98.14 ± 0.05, 98.19 ± 0.04, 97.01 ± 0.49, 84.43 ± 0.6% at 50 µM, respectively. Compounds 4 and 6 displayed significance against α-amylase at 200 µM with inhibition values of 22.35 ± 1.10 and 60.47 ± 0.91%.
Assuntos
Chamaecrista , Inibidores de Glicosídeo Hidrolases , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Hipoglicemiantes/farmacologia , alfa-Glucosidases/química , alfa-Amilases/química , Extratos Vegetais/química , Componentes Aéreos da Planta/químicaRESUMO
2,3,5,4'-Tetrahydroxy stilbene-2-Ο-ß-D-glucoside (TSG) and emodin (EMD) are two main components of Polygonum multiflorum Thunb. (PMT). Its root is widely used as herbal medicine and supplement. However, PMT-induced liver injury has drawn increasing attention. The purpose of this study was to investigate the interaction of TSG with EMD in the aspects of enzymology, pharmacokinetics, and hepatotoxicity. Co-administration with TSG increased internal exposure of EMD, EMD-derived hepatic protein adduction, and EMD-induced liver injury in mice. Mouse and human liver microsomal incubation study demonstrated that co-incubation with TSG decreased the formation of hydroxylation metabolites of EMD. Human recombinant cytochrome P450 enzyme incubation study showed that TSG induced time-, concentration-, NADPH-dependent and irreversible inhibition of CYP2C19 and CYP3A4. An epoxide metabolite derived from TSG was responsible for the observed enzyme inactivations. The findings allow us to better understand the mechanisms by which herbal processing detoxifies raw PMT.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Emodina , Glucosídeos , Estilbenos , Animais , Humanos , Camundongos , Citocromo P-450 CYP2C19 , Citocromo P-450 CYP3A , Emodina/toxicidade , Glucosídeos/farmacologia , Estilbenos/farmacologiaRESUMO
One unusual stilbene trimer-flavonoid hybrid, paeonilactiflobenoid (1), together with six known stilbenes (2-7) were isolated from the seeds of Paeonia lactiflora. The structure of 1 was elucidated with the aid of HRESIMS, 1D and 2D NMR, [α]D spectroscopic data and ECD calculation. Compounds 2-7 showed stimulative effects on GLP-1 secretion with promoting rates of 79.8%-880.4% (25 µM) and 217.6%-1089.4% (50 µM), more potent than the positive control, oleoylethanolamide (250.2% at 50 µM). Moreover, compounds 4 and 6 exhibited agonistic activity on the G protein-coupled receptor (GPCR) TGR5 with stimulative ratios of 40.2% and 40.5% at 50 µM, and 54.2% and 49.1% at 100 µM, respectively. Docking study manifested that 6 well located in the catalytic pocket of TGR5 by hydrogen-bond and hydrophobic interactions. The GLP-1 promotion of 6 could be attenuated by IP3, Ca2+/CaMKII and MEK/ERK pathway inhibitors, suggesting that these pathways played important roles in GLP-1 secretion. Thus, stilbenes in peony seeds maybe regarded as potential GLP-1 secretagogues through TGR5-IP3-Ca2+/CaMKII-MEK/ERK pathways.
Assuntos
Paeonia , Estilbenos , Paeonia/química , Peptídeo 1 Semelhante ao Glucagon , Secretagogos/análise , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/análise , Estrutura Molecular , Sementes/química , Estilbenos/farmacologia , Estilbenos/química , Quinases de Proteína Quinase Ativadas por Mitógeno/análiseRESUMO
Six undescribed stilbene derivatives Reflexanbene DH (1-4, 6) and Reflexanbene J (5), as well as one known stilbene 3,5-dimethoxystilbene (7), were isolated from the dried roots of Lindera reflexa Hemsl. Their structures and absolute configurations were elucidated using spectroscopy and electronic circular dichroism (ECD) analysis. In cytotoxic assays, moderately inhibitory activities of Reflexanbene F (3) against MGC80-3 and A549 cell lines were observed, with IC50 values of 15.42 and 5.09 µM, respectively. The IC50 value of Reflexanbene E (2) on A549 cell lines was 19.78 µM. The isolated compounds were also tested for their inhibitory effect against LPS-induced NO and IL-6 production in RAW 264.7 cells. In particular, Reflexanbene J (5) and Reflexanbene H (6) showed significant inhibition of NO production in LPS-stimulated macrophage RAW 264.7 cells at the concentration of 20 µM. Furthermore, the expression of IL-6 protein in the LPS-induced RAW 264.7 cells can also be significantly inhibited by different concentrations (5, 10 and 20 µM, p < 0.05 or p < 0.01) of compounds 1-7.
Assuntos
Anti-Inflamatórios , Antineoplásicos , Lindera , Estilbenos , Humanos , Anti-Inflamatórios/farmacologia , Interleucina-6 , Lindera/química , Lipopolissacarídeos , Estrutura Molecular , Estilbenos/farmacologia , Estilbenos/química , Células A549 , Células RAW 264.7 , Animais , Camundongos , Antineoplásicos/farmacologiaRESUMO
Neurodegenerative disorders are a critical affection with a high incidence around the world. Currently, there are no effective treatments to solve this problem. However, the application of mesenchymal stem cells (MSCs) and antioxidants in neurodegenerative diseases has shown to be a promising tool due to their multiple therapeutic effects. This work aimed to evaluate the effects of a combination of resveratrol (RSV) and coenzyme Q10 (CoQ10) on the proliferation and differentiation of MSC and the protector effects in induced damage. To characterize the MSCs, we performed flow cytometry, protocols of cellular differentiation, and immunocytochemistry analysis. The impact of RSV + CoQ10 in proliferation was evaluated by supplementing 2.5 and 10 µM of RSV + CoQ10 in a cellular kinetic for 14 days. Cell viability and lactate dehydrogenase levels (LDH) were also analyzed. The protective effect of RSV + CoQ10 was assessed by supplementing the treatment to damaged MSCs by 1-methyl-4-phenylpyridinium (MPP+); cellular viability, LDH, and reactive oxygen species (ROS) were evaluated.. MSCs expressed the surface markers CD44, CD73, CD90, and CD105 and showed multipotential ability. The combination of RSV + CoQ10 increased the proliferation potential and cell viability and decreased LDH levels. In addition, it reverted the effect of MPP+-induced damage in MSCs to enhance cell viability and decrease LDH and ROS. Finally, RSV + CoQ10 promoted the differentiation of neural progenitors. The combination of RSV + CoQ10 represents a potential treatment to improve MSCs capacities and protect against neurodegenerative damage.
RESUMO
Based on data from a previous ethnobotanical study in northern Angola, phytochemical investigations into the methanolic rhizomes and roots extract of Cyperus articulatus, monitored by in vitro assays, resulted in the recovery of 12 sesquiterpenes, 3 stilbenes, 2 phenolic acids, 1 monoterpene, and 1 flavonoid. Among them, 14 compounds were isolated for the first time from this species. Their inhibitory potential against nitric oxide (NO) production, as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, was evaluated in LPS-treated J774A.1 murine macrophages. Especially, both stilbene dimer trans-scirpusin B and trimer cyperusphenol B showed promising inhibitory activity against the production of the inflammatory mediator, NO, in a concentration-dependent manner (10−1 µM). The obtained data are the first results confirming the anti-inflammatory potential of C. articulatus and support its indigenous use as a traditional remedy against inflammation-related disorders.
Assuntos
Cyperus , Sesquiterpenos , Estilbenos , Animais , Anti-Inflamatórios/farmacologia , Bioensaio , Ciclo-Oxigenase 2/metabolismo , Cyperus/química , Flavonoides , Mediadores da Inflamação , Lipopolissacarídeos/farmacologia , Camundongos , Monoterpenos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Estilbenos/farmacologiaRESUMO
Eighteen stilbenes (1-18), including six previously undescribed ones (1-6), with diverse modification patterns were isolated from the leaves of edible and medicinal plant Cajanus cajan. Among the new isolates, compounds 1-3 were initially obtained as three racemic mixtures, which were further resolved into three pairs of optically pure enantiomers, respectively, by chiral HPLC. Besides, compounds 8, 10, 11, and 18 were obtained from C. cajan for the first time. The chemical structures and absolute configurations of the new stilbenes were elucidated unambiguously on the basis of extensive spectroscopic analyses, single crystal X-ray crystallographic study, and quantum chemical electronic circular dichroism (ECD) calculations. In addition, the in vitro anti-inflammatory activities of all isolated stilbenes were evaluated. Compounds 2, 9, 10, 11, and 14 exerted moderate suppression of nitric oxide (NO) secretion in lipopolysaccharide (LPS)-induced RAW264.7 cells without exhibiting substantial cytotoxicity.
Assuntos
Cajanus , Estilbenos , Anti-Inflamatórios/farmacologia , Cajanus/química , Estrutura Molecular , Folhas de Planta/química , Estilbenos/química , Estilbenos/farmacologiaRESUMO
Alzheimer's disease (AD) is a serious, progressive neurodegenerative disease that involves irreversible neuronal death. Tetrahydroxy stilbene glycoside (TSG) is an active compound extracted from P. multiflorum, a traditional Chinese herbal medicine, but its role in neuroprotection is unclear. Herein, we aimed to validate the effects of TSG on APP/PS1 model mice and the underlying mechanism. RNA-seq was performed to identify differentially expressed genes in APP/PS1 mouse, with PCR and immunohistochemistry used for validation. Experiments were performed after bioinformatic analysis for verification. Neuronal damage was observed by H&E staining. Key proteins involved in the pathway such as CX3CR1, Iba1 and TGF-ß were examined by immunohistochemical analysis. The KEGG analysis suggested that these genes might act by multiple pathways to build the pharmacological network of TSG in AD progression. These data provide the credible evidence that TSG improved neuronal damage and regulated neuroprotective mechanisms. Together, our work has detailed the whole and major genes in APP/PS1 model mouse regulated by TSG, and highlighted the anti-inflammatory function of TSG in mediating CX3CR1 and TGF-ß as the TGF-ß/fractalkine/CX3XR1 signaling pathway, especially in microglia. Moreover, TSG has potential value in synaptic transmission and neurotrophic action on neurodegenerative diseases. In summary, TSG is a promising candidate for preventing and treating the progression of AD.
Assuntos
Precursor de Proteína beta-Amiloide/genética , Anti-Inflamatórios não Esteroides/farmacologia , Receptor 1 de Quimiocina CX3C/genética , Quimiocina CX3CL1/genética , Fármacos Neuroprotetores/farmacologia , Oligopeptídeos/genética , Transdução de Sinais/efeitos dos fármacos , Estilbenos/farmacologia , Fator de Crescimento Transformador beta/genética , Doença de Alzheimer/tratamento farmacológico , Animais , Biologia Computacional , Progressão da Doença , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Transgênicos , RNA-Seq , Transdução de Sinais/genéticaRESUMO
Eight new stilbene dimer xylosides (1-8) and one new flavanol (9), along with seven known ones (10-16) were isolated from the roots of Lysidice rhodostegia. Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HR-ESI-MS, 1D and 2D NMR), ECD calculations and acid hydrolysis. Compounds 1-16 were evaluated for their antioxidant activities using DPPH radical-scavenging assay. Especially, compounds 9 and 10 exhibited stronger antioxidant effects than the positive control (vitamin E), with IC50 values of 9.57 ± 1.30 and 13.60 ± 1.47 µM, respectively.
Assuntos
Antioxidantes/farmacologia , Fabaceae/química , Glicosídeos/farmacologia , Polifenóis/farmacologia , Estilbenos/farmacologia , Antioxidantes/isolamento & purificação , China , Glicosídeos/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Polifenóis/isolamento & purificação , Estilbenos/isolamento & purificaçãoRESUMO
A series of azastilbene derivatives, characterized by the presence of the 1,2,4-oxadiazole-5-one system as a linker of the two aromatic rings of stilbenes, have been prepared as novel potential inhibitors of p38 MAPK. Biological assays indicated that some of the synthesized compounds are endowed with good inhibitory activity towards the kinase. Molecular modeling data support the biological results showing that the designed compounds possess a reasonable binding mode in the ATP binding pocket of p38α kinase with a good binding affinity.
Assuntos
Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases , Proteínas Quinases p38 Ativadas por Mitógeno , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/químicaRESUMO
Sophora davidii (Franch.) Skeels is a multi-purpose traditional medicine that has long been used for the treatment of various diseases. To discover the potential bioactive composition of S. davidii, a chemical investigation was thus performed. In this research, two new stilbene oligomers, Davidiol E-F (1-2), one new 4-aryl-substituted isoflavan Davidinin A (3), and one new 2-arylbenzofuran dimer, Shandougenine C (4), as well as six known compounds (5-10) were obtained from the ethyl acetate fraction of Sophora davidii (Franch.) Skeels. The structures of new compounds were established by extensive 1D and 2D nuclear magnetic resonance (NMR) spectra with mass spectroscopy data. The absolute configuration of 1-3 was assigned by comparing its experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1-10 promoted glucose transporter 4 (GLUT-4) translocations by the range of 1.28-2.60 folds, respectively. Compound 9 showed the most potent glucose transporter 4 translocations with 1.60 fold enhancement. The result attained in this study indicated that the separation and characterization of these compounds plays an important role in the research and development of new anti-diabetic drugs and pharmaceutical industry.
Assuntos
Transportador de Glucose Tipo 4/metabolismo , Raízes de Plantas/química , Sophora/química , Estilbenos/química , Estilbenos/farmacologia , Estrutura Molecular , Transporte Proteico , Estilbenos/análise , Estilbenos/isolamento & purificaçãoRESUMO
Propolis is a chemically complex resinous product collected from various plant sources by honeybees that has been used historically a traditional folk medicine in many parts of the world. The main constituents of propolis are beeswax and plant resins. We recently obtained Senegalese propolis, which, to our knowledge, has not been previously reported. The purpose of this study was to analyze the composition of Senegalese propolis and evaluate its anti-inflammatory activity. Ten known phenolic compounds with phenanthrene or stilbene skeletons were isolated. Nitric oxide (NO) production assay revealed that Senegalese propolis suppresses lipopolysaccharide (LPS)-stimulated production of NO in J774.1 cells in a dose-dependent manner. The anti-inflammatory potency of Senegalese propolis was higher than that of other previously reported propolis. Furthermore, the eight compounds isolated from Senegalese propolis showed high anti-inflammatory activity by inhibiting the LPS-induced expression of inducible NO synthase (iNOS). These results suggest that Senegalese propolis and its components have potential applications as anti-inflammatory agents.
Assuntos
Anti-Inflamatórios/farmacologia , Fenóis/farmacologia , Própole/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Abelhas , Linhagem Celular , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Fenantrenos/química , Fenóis/isolamento & purificação , Própole/química , Senegal , Estilbenos/químicaRESUMO
Cysestermerol A (1), a rare and new stilbene sestermer, was isolated from the whole herb of Cynodon dactylon. The planar and relative structures of 1 were elucidated based on HRESIMS, one- and two-dimensional NMR analyses, and its absolute configuration was further established by electronic circular dichroism calculations. Compound 1 obviously increased the glucose consumption in HepG2 cells equivalent to the positive control rosiglitazone and markedly inhibited the activity of α-glucosidase in vitro.