RESUMO
Four new lycoctonine-type C19-diterpenoid alkaloids kamaonensines H-K (1-4) have been isolated from the whole plants of Delphinium kamaonense, together with 12 known compounds (5-16). Interestingly, kamaonensines 1-3 contained a rare nitrone (immine N-oxide) moiety, respectively. Their structures were established by spectroscopic analyses. The active evaluation of compounds (1-16) by LPS induced RAW 264.7 macrophages showed that compounds 4 and 8 displayed strong anti-inflammatory activities. While compounds 11 and 12 also showed strong cytotoxicities by the RAW 264.7 cell viability assay.
RESUMO
Eight undescribed (1-8) and 46 known compounds (9-54) were isolated from the deep-sea-derived Aspergillus sp. MCCC 3A00392. Compounds 1-3 were three novel oxoindolo diterpenoids, 4-6 were three bisabolane sesquiterpenoids, while 7 and 8 were two monocyclic cyclopropanes. Their structures were established by exhaustive analyses of the HRESIMS, NMR, and theoretical calculations of the NMR data and ECD spectra. Compounds 10, 33, 38, and 39 were able to inhibit tumor necrosis factor (TNF)-induced necroptosis in murine L929 cell lines. Functional experiments verified that compounds 10 and 39 inhibited necroptosis by downregulating the phosphorylation of RIPK3 and MLKL. Moreover, compound 39 also reduced the phosphorylation of RIPK1. Compounds 10, 33, and 34 displayed potent inhibitory activities against RSL-3 induced ferroptosis with the EC50 value of 3.0 µM, 0.4 µM, and 0.1 µM, respectively. Compound 10 inhibited ferroptosis by the downregulation of HMOX1, while compounds 33 and 34 inhibited ferroptosis through regulation of NRF2/SLC7A11/GCLM axis. However, these compounds only showed weak effect in either the necroptosis or ferroptosis relative mouse disease models. Further studies of pharmacokinetics and pharmacodynamics might improve their in vivo bioactivities.
Assuntos
Ferroptose , Sesquiterpenos , Camundongos , Animais , Necroptose , Aspergillus/química , Sesquiterpenos/química , Sesquiterpenos MonocíclicosRESUMO
One new alkaloid, (S)-2-acetamido-4-(2-(methylamino)phenyl)-4-oxobutanoic acid (1), was isolated from the deep-sea-derived Penicillium citrinum XIA-16, together with 25 known compounds including ten polyketones (2-11), eight alkaloids (12-19), six steroids (20-25), and a fatty acid (26). Their planar and relative structures were determined by an analysis of 1D and 2D nuclear magnetic resonance (NMR) as well as high resolution electrospray ionization mass spectroscopy (HR-ESI-MS) data. The absolute configuration of 1 was determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Penicitrinol B (6) significantly inhibited RSL3-induced ferroptosis (EC50 =2.0â µM) by reducing lipid peroxidation and heme oxygenase 1 (HMOX1) expression. Under the concentration of 10â µM, penicitrinol A (7) was able to inhibit cuproptosis with the cell viabilities of 68.2 % compared to the negative control (copper and elesclomol) with the cell viabilities of 14.8 %.
Assuntos
Alcaloides , Antineoplásicos , Penicillium , Animais , Penicillium/química , Antineoplásicos/farmacologia , Espectroscopia de Ressonância Magnética/métodos , Alcaloides/química , Crustáceos , Estrutura MolecularRESUMO
Artemisia argyi is a widely distributed and inexpensive plant resource, and study on its chemical compositions and biological activities will provide an important basis for its food applications and pharmaceutical developments. In this study, fourteen known guaiane-type sesquiterpenes (1-14), four known eudesmane-type sesquiterpenes (15-18), two known germacranolide-type sesquiterpenes (19, 20), and eight other types of terpenoids (20-28) were isolated from the leaves of A. argyi by polyamide and ODS CC and HPLC. The structures of all compounds are determined by 1 D NMR (1H-NMRã13C-NMR) and literature comparison. Among them, compounds 1 and 8 were isolated from Chinese folk medicine A. argyi for the first time. Besides, the LPS-induced RAW264.7 cell model has been evaluated the anti-inflammatory activities in vitro by the Griess reagent. The results indicated that the guaianolide sesquiterpenoids obtained from A. argyi have an excellent ability to inhibit NO production, especially Argyin A, a guaianolide sesquiterpenoid with isovaleryloxy substitution.
Assuntos
Artemisia , Sesquiterpenos , Animais , Camundongos , Artemisia/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Células RAW 264.7RESUMO
Fifteen metabolites, including two flavonols (1-2), three lignans (3-5), and ten diterpenoids (6-15), were isolated from the leaves of Pinus yunnanensis. Among them, flavanonol (1) were identified as undescribed flavonol derivative with natural rarely B-ring fission lactone. Massive spectroscopic methods, the DP4+ probabilities and CD/ECD calculations were applied to establish the structure of component 1. Among these compounds, taxifolin (2) showed potent cytotoxicity, having IC50 values from 21.33 to 45.48â µg/mL, it also showed broad antibacterial activity against human pathogens with MIC values from 32 to 64â µg/mL.
Assuntos
Antibacterianos/química , Pinus/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Flavonóis/química , Flavonóis/isolamento & purificação , Flavonóis/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Conformação Molecular , Pinus/metabolismo , Extratos Vegetais/química , Folhas de Planta/química , Folhas de Planta/metabolismoRESUMO
In present study, multi-target and multi-pathway mechanisms of Jasminum lanceolarium Roxb (JL) on primary dysmenorrhea (PDM) treatment were predicted by the approach of network pharmacology and molecular docking, leading to the obtaining of 22 predicted targets for 69 compounds in JL. The Compound-Target analysis displayed intimate association among targets and compounds. Meanwhile, the Compound-Target-Target revealed PTGS2, OPRD1 and NOS3 were the key targets with intensive interaction. The Compound-Target-Pathway network indicated these pathways were closely related to hormone regulation, central analgesia, spasmolysis and inflammation. The anti-inflammation pathways might be the key mechanism of JL for the treatment of PDM based on KEGG pathway enrichment analysis and pharmacological experiment, and 10-hydroxyoleoside dimethyl ester might be a promising leading compound due to its good molecular docking scores and previous experimental evaluation.
Assuntos
Medicamentos de Ervas Chinesas , Jasminum , Medicamentos de Ervas Chinesas/farmacologia , Dismenorreia/tratamento farmacológico , Feminino , Humanos , Simulação de Acoplamento Molecular , Farmacologia em RedeRESUMO
Two new (1-2) as well as five known (3-7) compounds were isolated from Polytrichum commune, a folk herbal medicine in China, and three of them (2, 4, 5) belong to benzonaphthoxanthenones that are rarely found in nature. Their structures were elucidated by the approach to 1D and 2D NMR spectra. The absolute configuration of 2 was assigned by comparing its experimental and calculated ECD data. 1-5 were investigated for their anti-neuroinflammatory activity against LPS-induced BV-2 cells. 1 and 3 exhibited well protective effect at a concentration of 2.5 µmol/mL. Molecular docking studies were adopted to further investigate the possible mechanism, whose results suggested that 1 might exert anti-neuroinflammatory effect by inhibiting activity of p38α, JNK2 and TAK1 to reduce the liberation of pro-inflammatory cytokines.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Xantenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/análise , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Medicina Tradicional Chinesa , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Xantenos/química , Xantenos/isolamento & purificaçãoRESUMO
Six new guaiane-type sesquiterpenes (1-6), and one monoterpenoid (7) along with five known analogues (8-12), were isolated from the leaves of Artemisia argyi Lévl et Vant. The new compounds were characterized by the basic analysis of the spectroscopic data (HRMS, 1D and 2D NMR), and the absolute configurations were determined by both calculated electronic circular dichroism and DP4 calculations. The inhibitory effects of 1-12 against human gastric adenocarcinoma (AGS) cells were investigated in vitro, among which 1-3 and 8 showed remarkable cytotoxic activity with IC50 values in the range of 6.69-10.25 µM. The results suggested that the variation in the inhibitory activities of the compounds are the result of different substitutions on C-8. In order to rationalize the binding interactions of active compounds with the active site of NF-кB, in silico study was conducted and the results were in complete agreement with the experimental data for cytotoxicity evaluation.
Assuntos
Adenocarcinoma/patologia , NF-kappa B/antagonistas & inibidores , Sesquiterpenos de Guaiano/farmacologia , Neoplasias Gástricas/patologia , Humanos , Análise Espectral/métodos , Células Tumorais CultivadasRESUMO
Five new isoquinolines (1-5) were isolated from national herb Corydalis tomentella. Their structures were elucidated by extensive analysis of the 1D and 2D NMR spectra and from the HRESIMS. Absolute configurations of 1-3 were determined by comparing their experimental and computed ECD data. Since plants from Corydalis have been reported to protect against Alzheimer's disease, all compounds were evaluated for their neuroprotective effect against lipopolysaccharide-induced BV2 microglia cells. Compound 2 and 3 showed well anti-neuroinflammatory activity at low concentration (25 µM).
Assuntos
Doença de Alzheimer/tratamento farmacológico , Corydalis/química , Isoquinolinas/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Isoquinolinas/química , Isoquinolinas/isolamento & purificação , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Stauntonia brachyanthera Hand.-Mazz. (SB), reported as a traditional Chinese medicine, displays a wide spectrum of interesting bioactivities, such as anti-inflammatory and analgesia. It is noteworthy that anti-gout effects of the components in SB have been reported. Hence, this study contributes to the prediction of promising active compounds and mechanisms for the treatment of gout. The active compounds with better oral bioavailability, and drug-likeness of SB were selected for further investigation by the approach of network pharmacology, molecular docking, gene ontology (GO) analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, respectively. A total of 34 predicted targets and 98 compounds in SB were obtained. Sorted by structure types of compounds, phenylethanoid glycosides exhibited the best anti-gout activity, followed by phenolics and flavonoids. What's more, it was shown in the network analysis that Serine/threonine-protein kinase mTOR (mTOR), Mitogen-activated protein kinase 12 (MAPK12), tumor necrosis factor (TNF-α), Integrin alpha-4 (ITGA4) and Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG) were the key targets with intensely interaction, which should be attached more attention for further study. The functional enrichment analysis indicated that SB probably produced the anti-gout effects by synergistically regulating many biological pathways, such as MAPK signaling pathway, PI3K-Akt signaling pathway, Toll-like receptor signaling pathway and NOD-like receptor signaling pathway, etc. In addition, C61, C67, C68 and C81 might be promising leading compounds with good molecular docking score. As a consequence, the active constituents and mechanisms based on data analysis were holistically illuminated, which was of vital importance to the development of new drugs for gout.
Assuntos
Anti-Inflamatórios/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Gota/tratamento farmacológico , Magnoliopsida/química , Extratos Vegetais/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Gota/metabolismo , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Estrutura Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Ohwia caudata (OC)-a traditional Chinese medicine (TCM)-has been reported to have large numbers of flavonoids, alkaloids, and triterpenoids. The previous studies on OC for treating Alzheimer's disease (AD) only focused on single targets and its mechanisms, while no report had shown about the synergistic mechanism of the constituents from OC related to their potential treatment on dementia in any database. This study aimed to predict the bioactive targets constituents and find potential compounds from OC with better oral bioavailability and blood-brain barrier permeability against AD, by using a system network level-based in silico approach. The results revealed that two new flavonoids, and another 26 compounds isolated from OC in our lab, were highly connected to AD-related signaling pathways and biological processes, which were confirmed by compound-target network, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, respectively. Predicted by the virtual screening and various network pharmacology methods, we found the multiple mechanisms of OC, which are effective for alleviating AD symptoms through multiple targets in a synergetic way.
Assuntos
Doença de Alzheimer , Medicamentos de Ervas Chinesas/farmacologia , Fabaceae/química , Regulação da Expressão Gênica/efeitos dos fármacos , Ontologia Genética , Redes Reguladoras de Genes/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Disponibilidade Biológica , Medicamentos de Ervas Chinesas/química , HumanosRESUMO
Artemisia argyi (AA) is one of the renowned herbs in China often used in the treatment of gastric ulcer (GU). Aiming to predict the active compounds and systematically investigate the mechanisms of Artemisia argyi for GU treatment, the approach of network pharmacology, molecular docking, gene ontology (GO) analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were adopted, respectively, in present study. A total of 13 predicted targets of the 103 compounds in Artemisia argyi were obtained. Sorted by pathogenic mechanisms of targets and structure types of compounds, it was revealed that flavonoids and sesquiterpenes had better performance than monoterpenes. The network analysis showed that Phospholipase a2 (PA21B), Sulfotransferase family cytosolic 2b member 1 (ST2B1), Nitric-oxide synthase, endothelial (NOS3), Gastrin (GAST), neutrophil collagenase (MMP-8), Leukotriene A-4 hydrolase (LKHA4), Urease maturation factor HypB (HYPB), and Periplasmic serine endoprotease DegP (HtrA) were the key targets with intensely interaction. The functional enrichment analysis indicated that AA probably produced the gastric mucosa protection effects by synergistically regulating many biological pathways, such as NF-κB signaling pathway, HIF-1 signaling pathway, TNF signaling pathway, VEGF signaling pathway, and Toll-like receptor signaling pathway, etc. In addition, C73 and C15 might be promising leading compounds with good molecular docking score. As a consequence, this study holistically illuminates the active constituents and mechanisms based on data analysis, which contributes to searching for leading compounds and the development of new drugs for gastric ulcer.
Assuntos
Antiulcerosos/metabolismo , Artemisia/química , Farmacologia/métodos , Proteínas/metabolismo , Antiulcerosos/química , Simulação de Acoplamento Molecular , Ligação Proteica , Proteínas/química , Transdução de SinaisRESUMO
BACKGROUND@#Herpes virus is considered to be the pathogen of acute retinal necrosis (ARN) infection. Previous studies have found that patients with ARN caused by the varicella-zoster virus (VZV) are often older, and patients with herpes simplex virus (HSV) induced ARN are considerably younger. However, in our clinical work, we find that VZV is also a pathogen in younger ARN patients. We, therefore, aimed to analyze the common etiology of younger ARN patients.@*METHODS@#A retrospective analysis was made of 20 eyes (18 patients) diagnosed as having ARN in the Department of Ophthalmology of Peking Union Medical College Hospital from 2014 to 2016. All patients were reviewed for demographic data, clinical course, clinical manifestations, time from onset to initial physician visit, duration of follow-up, visual acuity at both presentation and final visit, and treatment strategies. A paired t test was used to compare visual acuity between the presenting vision and those of final follow-up. Vitreous or aqueous specimens from 18 eyes of 18 patients were analyzed with multiplex polymerase chain reaction (mPCR)/quantitative PCR (qPCR) and xTAG-liquid chip technology (xTAG-LCT) to determine the causative virus of ARN.@*RESULTS@#Final best visual acuity (BCVA) improved significantly from 1.36 ± 0.95 (median 20/400) to 0.95 ± 0.82 (median 20/100) (t = 2.714, P = 0.015) after systemic and intravitreal antiviral treatment combined with or without pars plana vitrectomy. PCR and xTAG-LCT results showed four of the five samples in the younger group (32.2 ± 5.2 years) and 12 of the 13 samples in the senior group (53.6 ± 4.9 years) were positive for VZV, and two of the five samples in the younger group were positive for HSV-1.@*CONCLUSIONS@#This study demonstrates that VZV is also a common causative virus for ARN in younger patients. Considering this finding, a systemic antiviral treatment protocol should be immediately changed to intravenous ganciclovir when the patient does not respond to acyclovir before determining the causative virus, especially in younger patients.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Etários , Herpesvirus Humano 3 , Virulência , Síndrome de Necrose Retiniana Aguda , Virologia , Estudos Retrospectivos , Infecção pelo Vírus da Varicela-Zoster , Acuidade Visual , FisiologiaRESUMO
Xueshuantong Lyophilized Powder (XST), consisting of a series of saponins extracted from Panax notoginseng, is widely applied to treat acute cerebral infarction, stroke, and coronary heart disease in China. However, most adverse drug reactions (ADR) in clinic are caused by quality problems of XST. In this study, six batches of certainly abnormal, four batches of possibly abnormal XST, and eight batches of normal XST were obtained from the clinical practice. Their quality fluctuations were identified by ultra-performance liquid chromatography coupled with an electrospray ionization quadrupole time-of-flight mass spectrometry operating in MSE mode (UPLC-QTOF/MSE) and bioassays including antithrombin and proplasmin assay. Fourteen potential components responsible for clinical ADR were identified by UPLC-QTOF/MSE, especially ginsenoside Rg1, Rg3, Rb1 and notoginsenoside R1. In addition, 83.3% (5/6) and 50.0% (3/6) certainly abnormal samples could be identified by UPLC-QTOF/MSE and bioassay, respectively. Interestingly, further integration of the two methods could entirely identify all the certainly abnormal samples and inferred that all the possibly abnormal samples were closely related to their quality fluctuation. It indicates that it is advisable to combine UPLC-QTOF/MSE and bioassay for identifying quality fluctuation of XST, and thus reduce its ADR in clinic.
RESUMO
This study described a valuable drug delivery system for poorly water-soluble anticancer naturalproduct, licochalcone A, isolated from Glycyrrhiza inflata, loaded on hollow gold nanoparticles by green method to improve solubility and dissolution and maintain its natural pharmacological property. Briefly, the formation of hollow gold nanoparticles involves three steps: preparing of silica nanospheres by Stober method, forming of a thick gold shell around the silica templates and etching of silica particles by HF solution. Hollow gold nanoparticles (HGNPs) and drug loaded hollow gold nanoparticles (L-HGNPs) displayed spherical structure and approximately 200nm in size observed by SEM, XRD, EDS and DSC analysis showed that HGNPs were gold hollow structure and crystalline form. The solubility in aqueous solution of licochalcone A was increased obviously to 488.9 µg/ml, compared with free drugs of 136.1 µg/ml. Another interesting finding is that near-infrared (NIR) irradiation increased the speed of solubility of licochalcone A in aqueous solutions, rather than quantity. In short, the method of nano-delivery system combined with poorly water-soluble drug to improve its solubility and dissolution is worth applying to other natural products in order to increase their opportunities in clinical applications.
RESUMO
BACKGROUND: X. sorbifolia is a widely cultivated ecologicalcrop in the north of China which is used to produce biodiesel fuel. It also possesses special medicinal value and has attracted keen interests of researchers to explore its bioactivity. PURPOSE: To extract the total triterpenoid saponins from the husk of X. sorbifolia (TSX) and investigate its effects on Alzheimer's disease (AD). STUDY DESIGN: TSX was prepared via modern extraction techniques. Its effects on two AD animal models, as well as the preliminary mechanism were investigated comprehensively. METHODS: The behavioral experiments including Y maze test, Morris water maze test and passive avoidance test were performed to observe the learning and memory abilities of the animals. ELISA assays, transmission electron microscope observation and Western blotting were employed in mechanism study. RESULTS: TSX, the main composition of X. sorbifolia, accounted for 88.77% in the plant material. It could significantly increase the spontaneous alternation in Y maze test (F (6, 65)=3.209, P<0.01), prolong the swimming time in the fourth quadrant in probe test of Morris water maze test (F (6, 71)=4.019, P<0.01), and increase the escape latency in passive avoidance test (F (6, 65)=3.684, P<0.01) in AD model animals. The preliminary mechanism research revealed that TSX could significantly increase the contents of hippocampal Ach and ChAT, and enhance activity of ChAT in hippocampus of quinolinic acid injected rats (F (5, 61)=3.915, P 0.01; F (5, 61)=3.623, P<0.01, F (5, 61)=4.344, P<0.01, respectively). It could also increase the activities of T-AOC and T-SOD, and decrease the content of MDA in hippocampus of Aß1-42 injected mice (F (5, 30)=5.193, P<0.01, F (5, 30)=2.865, P<0.05, F (5, 30)=4.735, P<0.01, respectively). Moreover, it significantly increased the expressions of SYP, PSD-95 and GAP-43 in hippocampus (F (4, 27)=3.495, P<0.05; F (4, 27)=2.965, P<0.05; F (4, 27)=4.365, P<0.01, respectively), and improved the synaptic ultra-structure damage in model rats. CONCLUSION: TSX could significantly improve the impairments of learning and memory. The preliminary mechanism might associate with its protection effects against oxidative stress damage, cholinergic system deficiency and synaptic damage. TSX are perfectly suitable for AD patients as medicine or functional food, which would be a new candidate to treat AD.
Assuntos
Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória , Estresse Oxidativo/efeitos dos fármacos , Sapindaceae/química , Saponinas/farmacologia , Sinapses/patologia , Triterpenos/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , China , Cognição/efeitos dos fármacos , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Transtornos da Memória/patologia , Camundongos , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Sinapses/ultraestrutura , Triterpenos/uso terapêuticoRESUMO
With the aim of finding more potential anti-gout compounds from natural resources, a phytochemical study on the leaves of Stauntonia brachyanthera was carried out, which led to the isolation of 11 nor-oleanane triterpenoids, including 4 new ones. Their structures were determined by the comprehensive 1D, 2D NMR, HRMS, and HPLC analysis after acid hydrolysis. Brachyantheraoside B4 (3) and 3-O-α-l-rhamnopyranosyl-(1â2)-α-l-arabinopyranosyl-30-norolean-12,20(29)-dien-28-oic acid (8) exhibited significant inhibitory activities on xanthine oxidase with IC50 values of 0.20 and 18.5µM, respectively. Brachyantheraoside C2 (2) also showed moderate effects on XO. A primary structure-activity relationship was also summarized, which revealed the anti-gout abilities of three nor-oleanane triterpenoids and their potential possibilities as the candidate compounds for the treatment of gout. The discovery of nor-oleanane triterpenoids also widens people's idea for the study of anti-gout agents and promotes the comprehensive development of S. brachyanthera.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Gota/tratamento farmacológico , Magnoliopsida/química , Ácido Oleanólico/análogos & derivados , Folhas de Planta/química , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Humanos , Estrutura Molecular , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Relação Estrutura-AtividadeRESUMO
The inhibition of UDP-glucuronosyltransferases (UGTs) by herbal components might be an important reason for clinical herb-drug interaction (HDI). The inhibitory effects on UGTs via nor-oleanane triterpenoid saponins, which were the bioactive ingredients from Stauntonia brachyanthera, a traditional Chinese folk medicines with highly biological values, were evaluated comprehensively with recombinant UGT isoforms as enzyme source and a nonspecific substrate 4-methylumbelliferone (4-MU) as substrate. The results showed that there are seven compounds, 2, 3, 4, 8, 9, 13 and 14, respectively, exhibited potential inhibitions towards UGT1A1, UGT1A3 and UGT1A10 among all 23 compounds isolated from the plants. The IC50 values were 17.1µM, 13.5µM, 9.5µM, 15.7µM, 16.3µM, 1.1µM, and 0.3µM, respectively. Data fitting using Dixon and Lineweaver-Burk plots demonstrated that the inhibition of UGT1A10, UGT1A1 and UGT1A3 was best fit to noncompetitive type and competitive, respectively. The inhibition kinetic parameter (Ki) was calculated to be 39µM, 17µM, 3.3µM, 10µM, 9.3µM, 0.19µM, and 0.016µM, respectively. All these experimental data suggested that HDI might occur when compounds containing herbs were co-administered with drugs which mainly undergo UGTs-mediated metabolism.
Assuntos
Glucuronosiltransferase/antagonistas & inibidores , Magnoliopsida/química , Ácido Oleanólico/análogos & derivados , Saponinas/química , Medicamentos de Ervas Chinesas , Interações Ervas-Drogas , Estrutura Molecular , Ácido Oleanólico/químicaRESUMO
In order to increase the solubility of poorly water-soluble natural product, xanthoceraside, an effective anti-AD compound from Xanthoceras sorbifolia Bunge, and maintain its natural property, the xanthoceraside hollow gold nanoparticles were successively prepared by green ultrasonic method with silica spheres as templates and HF solution as selective etching solvent. Hollow gold nanoparticles and drug-loaded hollow gold nanoparticles were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The solubilities of xanthoceraside loaded on hollow gold nanoparticles were increased obviously from 3.0µg/ml and 2.5µg/ml to 12.7µg/ml and 10.7µg/ml at 25°C and 37°C, respectively. The results of XRD and DSC indicated that the reason for this increase was mainly due to the amorphous state of xanthoceraside loaded on the hollow gold nanoparticles. In summary, the method of loading xanthoceraside onto hollow gold nanoparticles was a green and useful strategy to improve the solubility and dissolution of poorly water-soluble natural products and worth to applying to other natural products.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Ouro/química , Nanopartículas Metálicas/química , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/química , Saponinas/química , Triterpenos/química , Água/química , Varredura Diferencial de Calorimetria/métodos , Portadores de Fármacos/química , Microscopia Eletrônica de Varredura/métodos , Dióxido de Silício/química , Solubilidade , Tecnologia Farmacêutica/métodos , Difração de Raios X/métodosRESUMO
Ten ent-abietane diterpenoids (1-10), including four new (1-4) and six known ones (5-10) were isolated from the roots of Euphorbia ebracteolata. Their structures were determined by 1D, 2D NMR, and HRESIMS. Compounds 2, 4, and 7 exhibited significant inhibitory activities on lipopolysaccharide (LPS)-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 0.69, 1.97, and 0.88µM, respectively. A primary structure-activity relationship was also discussed.