RESUMO
BACKGROUND: Sepsis is a leading cause of death among critically ill patients, which is defined as life-threatening organ dysfunction caused by a deregulated host immune response to infection. Immune checkpoint molecule Tim-3 plays important and complex roles in regulating immune responses and in inducing immune tolerance. Although immune checkpoint blockade would be expected as a promising therapeutic strategy for sepsis, but the underlying mechanism remain unknown, especially under clinical conditions. METHODS: Tim-3 expression and apoptosis in NKT cells were compared in septic patients (27 patients with sepsis and 28 patients with septic shock). Phenotypic and functional characterization of Tim-3+ NKT cells were analysed, and then the relationship between Tim-3 + NKT cells and clinical prognosis were investigated in septic patients. α-lactose (Tim-3/Galectin-9 signalling inhibitor) and Tim-3 mutant mice (targeting mutation of the Tim-3 cytoplasmic domain) were utilized to evaluate the protective effect of Tim-3 signalling blockade following septic challenge. RESULTS: There is a close correlation between Tim-3 expression and the functional status of NKT cells in septic patients, Upregulated Tim-3 expression promoted NKT cell activation and apoptosis during the early stage of sepsis, and it was associated with worse disease severity and poorer prognosis in septic patients. Blockade of the Tim-3/Galectin-9 signal axis using α-lactose inhibited in vitro apoptosis of NKT cells isolated from septic patients. Impaired activity of Tim-3 protected mice following septic challenge. CONCLUSIONS: Overall, these findings demonstrated that immune checkpoint molecule Tim-3 in NKT cells plays a critical role in the immunopathogenesis of septic patients. Blockade of immune checkpoint molecule Tim-3 may be a promising immunomodulatory strategy in future clinical practice for the management of sepsis.
Assuntos
Células T Matadoras Naturais , Sepse , Animais , Camundongos , Apoptose , Galectinas/metabolismo , Galectinas/farmacologia , Galectinas/uso terapêutico , Receptor Celular 2 do Vírus da Hepatite A , Proteínas de Checkpoint Imunológico/farmacologia , Proteínas de Checkpoint Imunológico/uso terapêutico , Lactose/farmacologiaRESUMO
Coronavirus disease 2019 (COVID-19) pathogenesis is influenced by reactive oxygen species (ROS). Nevertheless, the precise mechanisms implicated remain poorly understood. The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the main driver for this condition, is a structural protein indispensable for viral replication and assembly, and its role in ROS production has not been reported. This study shows that SARS-CoV-2 N protein expression enhances mitochondrial ROS level. Bulk RNA-sequencing suggests of aberrant redox state of the electron transport chain. Accordingly, this protein hinders ATP production but simultaneously augments the activity of complexes I and III, and most mitochondrially encoded complex I and III proteins are upregulated by it. Mechanistically, N protein of SARS-CoV-2 shows significant mitochondrial localization. It interacts with mitochondrial transcription components and stabilizes them. Moreover, it also impairs the activity of antioxidant enzymes with or without detectable interaction.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/metabolismo , Espécies Reativas de Oxigênio , Proteínas do Nucleocapsídeo/química , Replicação ViralRESUMO
Gold nanoclusters (AuNCs) are a unique class of materials that exhibit visible luminescence. Amorphous calcium phosphate (ACP) is a widely used biomaterial for a variety of purposes, such as drug delivery, bone cementing, and implant coatings. In this study, a nanocomposite of AuNCs and ACP is prepared by biomimetic mineralization in a Dulbecco's modified Eagle's medium (DMEM). The strong interaction between AuNCs and Ca2+ ions effectively induces aggregation of AuNCs. The as-formed nanocomposite, AuNCs@ACP, emits significantly enhanced luminescence compared to AuNCs alone. The luminescence enhancement mechanism is investigated using synchrotron X-ray absorption fine structure spectroscopy. In addition, the presence of AuNCs stabilizes ACP and also enhances the biocompatibility of ACP in promoting cell proliferation, and the nanocomposites are promising as nanoprobes for cancer therapy and/or bone tissue engineering.
Assuntos
Biomimética , Ouro , Fosfatos de CálcioRESUMO
Alzheimer's disease (AD) is regarded as a progressive neurodegenerative dementia, characterized by degeneration of distinct neuronal populations. A case-control study was carried out using high-resolution mass spectrometry to explore AD-associated urinary metabolic biomarkers from 30 AD patients and 30 cognitively normal (CN) individuals. In total, 49 metabolites were determined and validated as known compounds using LC/MS analysis. Using the two-sample t-test statistical analysis (P < 0.05), 19 metabolites were shown to be significantly different from AD to CN. A diagnostic model of the receiver operating characteristic curve was constructed with a combination of nine molecules out of 19 metabolites, it yielded a separation with an area under the curve value of 0.976 between the two groups. This study indicated that urinary metabolites showed a significant expression between AD and CN. AD-related metabolites enable to satisfy the diagnostic power of disease discrimination. In addition, as a noninvasive approach, urine collection is done easily in clinical diagnosis of AD.
Assuntos
Doença de Alzheimer , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Humanos , Espectrometria de Massas , Curva ROCRESUMO
Osteoporosis (OP) is a systemic bone disease characterized by decreased bone strength, microarchitectural changes in bone tissues, and increased risk of fracture. Its occurrence is closely related to various factors such as aging, genetic factors, living habits, and nutritional deficiencies as well as the disturbance of bone homeostasis. The dysregulation of bone metabolism is regarded as one of the key influencing factors causing OP. Cholesterol oxidation products (COPs) are important compounds in the maintenance of bone metabolic homeostasis by participating in several important biological processes such as the differentiation of mesenchymal stem cells, bone formation in osteoblasts, and bone resorption in osteoclasts. The effects of specific COPs on mesenchymal stem cells are mainly manifested by promoting osteoblast genesis and inhibiting adipocyte genesis. This review aims to elucidate the biological roles of COPs in OP development, starting from the molecular mechanisms of OP, pointing out opportunities and challenges in current research, and providing new ideas and perspectives for further studies of OP pathogenesis.
Assuntos
Colesterol/metabolismo , Osteoporose/metabolismo , Osteoporose/patologia , Animais , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Humanos , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteogênese/fisiologia , OxirreduçãoRESUMO
A series of pyrano[3,2-a]carbazole alkaloids were designed and synthesized as derivatives of Girinimbine. The anticancer activities of these derivatives (3, 4a-j, 5a, 5c, 5f, 5i, 6c, 7a, 7c, 7f, 7i) against 10 cancer cell lines were studied. Among them, compounds 3 and 7i with N-methyl piperazine showed significant anticancer activity against MCF-7 cell lines with the IC50 values of 1.77 and 4.32 µM, respectively. Furthermore, their effects on altering cell morphology, inducing cell cycle arrest and apoptosis in MCF-7 cells were studied in vitro. In addition, the molecular docking study was carried out by using Discovery Studio software to predict the interactions between these derivatives and tubulin. All in all, these consequences reveal that pyranocarbazole derivatives with N-methyl piperazine can be used as potential anticancer lead compounds and provide useful points for the further optimization of pyranocarbazole alkaloids.
Assuntos
Antineoplásicos/farmacologia , Carbazóis/farmacologia , Piranos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Carbazóis/síntese química , Carbazóis/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Piranos/síntese química , Piranos/química , Relação Estrutura-AtividadeRESUMO
Nine undescribed monoterpene phenol dimers, bisbakuchiols D-L (1-9), were isolated from the fruits of Psoralea corylifolia L. Their structures were elucidated based on extensive spectral analysis. The absolute configurations of 1-9 were specified by experimental and quantum chemical calculations of ECD spectra, and that of 1 was further established by X-ray diffraction analysis using Cu Kα radiation. Bisbakuchiols (1-4) were composed of two bakuchiols, one of which was cyclized via a C-7'/ C-12' single bond to form a six-member ring, and connect to each other by C-4-O-C-13' bonds. Bisbakuchiols (7-9) had a pyran ring by linkage of C-8-O-C-12. In the enzyme assay, compounds 5 and 9 exhibited significant PTP1B inhibitory activities with IC50 values of 0.69 and 0.73 µM, and compounds 1 and 3 showed moderate PTP1B inhibitory activities. Furthermore, a molecular docking simulation of PTP1B and active compounds 5 and 9 showed that these active compounds possess low binding affinities ranging from -6.9 to -7.1 kcal/mol.
Assuntos
Inibidores Enzimáticos/farmacologia , Frutas/química , Monoterpenos/farmacologia , Fenóis/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Psoralea/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Monoterpenos/química , Monoterpenos/isolamento & purificação , Fenóis/química , Fenóis/isolamento & purificação , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Hypertensive cerebral hemorrhage seriously endangers the health of the elderly. However, the relationship between obesity and arterial elasticity in hypertensive cerebral hemorrhage remains to be clarified. The purpose of our study is to explore the associations between body mass index (BMI) and central arterial reflected wave augmentation index (cAIx), toe-brachial index (TBI), brachial-ankle pulse wave velocity (baPWV), and ankle-brachial index (ABI) in the elderly hypertensive patients with hemorrhagic stroke. MATERIALS AND METHODS: A total of 502 elderly hypertensive patients with hemorrhagic stroke and 100 healthy controls were collected. According to the BMI, patients were divided into normal BMI, overweight, obesity, and obese groups. The multivariate logistic regression model was used to establish a risk model for elderly hypertensive hemorrhagic stroke. RESULTS: Compared with the normal BMI group, systolic blood pressure (SBP), diastolic blood pressure (DBP), cAIx, and baPWV in the abnormal BMI group were significantly increased (P < 0.05), while TBI and ABI were significantly decreased (P < 0.05). Logistic regression showed that BMI (OR = 1.031, 95%CI: 1.009-1.262), cAIx (OR = 1.214, 95%CI: 1.105-1.964), TBI (OR = 0.913, 95%CI: 0.885-0.967), baPWV (OR = 1.344, 95%CI: 1.142-2.147), and ABI (OR = 0.896, 95%CI: 0.811-0.989) are important factors for the occurrence of hemorrhagic stroke in the elderly hypertensive patients. ROC curve analysis showed that the AUC of cAIx, TBI, baPWV, ABI, and BMI were 0.914, 0.797, 0.934, 0.833, and 0.608, respectively. The final prediction model of hemorrhagic stroke elderly hypertensive patients was Y(P)= 65.424 + 0.307(cAIx) - 13.831(TBI) + 0.012(baPWV) - 0.110(ABI) + 0.339(BMI). CONCLUSIONS: Obesity is associated with decreased arterial elasticity. Therefore, reasonable weight management of the elderly may be of great significance for reducing the risk of hemorrhagic stroke in patients with hypertension.
Assuntos
Índice Tornozelo-Braço , Pressão Sanguínea , Índice de Massa Corporal , Acidente Vascular Cerebral Hemorrágico/diagnóstico , Hipertensão/diagnóstico , Hemorragia Intracraniana Hipertensiva/diagnóstico , Obesidade/diagnóstico , Doença Arterial Periférica/diagnóstico , Análise de Onda de Pulso , Rigidez Vascular , Fatores Etários , Idoso , Estudos de Casos e Controles , China/epidemiologia , Feminino , Acidente Vascular Cerebral Hemorrágico/epidemiologia , Acidente Vascular Cerebral Hemorrágico/fisiopatologia , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Hemorragia Intracraniana Hipertensiva/epidemiologia , Hemorragia Intracraniana Hipertensiva/fisiopatologia , Masculino , Obesidade/epidemiologia , Obesidade/fisiopatologia , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco , Fatores de RiscoRESUMO
The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A total of 26 Claulansine F-donepezil hybrids were designed and synthesized as multitarget drugs. Among these compounds, six compounds exhibited excellent acetylcholinesterase (AChE) inhibitory activity (half maximal inhibitory concentration (IC50) 1.63-4.62 µM). Moreover, (E)-3-(8-(tert-Butyl)-3,3-dimethyl-3,11-dihydropyrano[3,2-a]carbazol-5-yl)-N-((1-(2-chlorobenzyl)piperidin-4-yl)methyl)acrylamide (6bd) exhibited better neuroprotective effects against OGD/R (oxygen-glucose deprivation/reoxygenation) than lead compound Claulansine F. Furthermore, 6bd could cross the blood-brain barrier in vitro. More importantly, compared to edaravone, 6bd had stronger free-radical scavenging activity. Molecular docking studies revealed that 6bd could interact with the catalytic active site of AChE. All of these outstanding in vitro results indicate 6bd as a leading structure worthy of further investigation.
Assuntos
Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Carbazóis/química , Inibidores da Colinesterase/química , Donepezila/química , Fármacos Neuroprotetores/química , Animais , Barreira Hematoencefálica/metabolismo , Carbazóis/farmacologia , Inibidores da Colinesterase/farmacologia , Donepezila/farmacologia , Desenho de Fármacos , Quimioterapia Combinada , Sequestradores de Radicais Livres/metabolismo , Glucose/metabolismo , Humanos , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Fármacos Neuroprotetores/farmacologia , Oxigênio/metabolismo , Ratos Sprague-DawleyRESUMO
Seven flavonoid dimers, biflavocochins A-G, together with six known compounds were isolated from the red resins of Dracaena cochinchinensis (Chinese dragon's blood). Their structures were elucidated based on extensive spectroscopic analysis. The absolute configurations of 1-7 was assigned by experimental and quantum chemical calculated ECD spectra, and that of 4 was further established by X-ray diffraction analysis using Cu Kα radiation. Compounds 1-3 are novel dimers of homoisoflavonoid and dihydrochalcone with a unique dibenzopyran ring. Compounds 2, 6, 7 exhibited moderate PTP1B inhibitory activities in an enzyme assay. Compound 1 showed neuroprotective effect on serum deficiency-induced cellular damage in PC12 cells.
Assuntos
Dracaena/química , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Animais , Cristalografia por Raios X , Dimerização , Inibidores Enzimáticos/química , Flavonoides/química , Humanos , Modelos Moleculares , Fármacos Neuroprotetores/química , Células PC12 , Extratos Vegetais/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , RatosRESUMO
Two new saponins, notoginsenosides Ng1 (1) and Ng2 (2), together with seven known compounds (3-9), were isolated from the leaves of Panax notoginseng. Their structures were elucidated by UV, IR, HRESIMS, and NMR experiments. Compounds 6 and 7 showed moderate cytotoxic activities against HCT-116, with IC50 values of 4.98 and 0.64 µmol/L, respectively.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Panax notoginseng/química , Saponinas/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Células HCT116 , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química , Saponinas/química , Saponinas/farmacologiaRESUMO
Three new C-methylated phenylpropanoid glycosides (1, 2), a new 8-4'-oxyneolignan (3), together with two known analogs (4, 5), were isolated from the rhizomes of Imperata cylindrical Beauv. var. major (Nees) C. E. Hubb. Their structures were determined by spectroscopic and chemical methods. Compounds 1, 2, and 5 (10 µM) exhibited pronounced hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage in vitro assays. Furthermore, their antioxidant activities against Fe2+-cysteine-induced rat liver microsomal lipid peroxidation and the effects on the secretion of TNF-α in murine peritoneal macrophages (RAW264.7) induced by lipopolysaccharides were evaluated.
Assuntos
Glicosídeos/química , Glicosídeos/farmacologia , Poaceae/química , Rizoma/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Peroxidação de Lipídeos , Macrófagos/efeitos dos fármacos , Camundongos , Microssomos Hepáticos/efeitos dos fármacos , Células RAW 264.7 , RatosRESUMO
Three 18(4â3)-abeo-abietanoids, a new natural product and two new compounds, named tripordolides Aâ»C (1â»3), were isolated from the leaves of Tripterygium wilfordii. Their structures were elucidated on the basis of their spectroscopic analysis, and the absolute configuration of compounds was confirmed by CD and X-ray crystallographic analysis using anomalous scattering of Cu Kα radiation. Compounds 1 and 3 showed moderate inhibitory activities against NO production in lipopolysaccharide-induced (LPS) RAW 264.7 macrophages in vitro.
Assuntos
Abietanos/farmacologia , Macrófagos/efeitos dos fármacos , Óxido Nítrico/análise , Extratos Vegetais/farmacologia , Folhas de Planta/química , Tripterygium/química , Animais , Células Cultivadas , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismoRESUMO
Further study on the constituents from the stems of Hydrangea paniculata Sieb resulted in isolation of two new compounds 1-2, including 1 monoterpenoid and 1 phenolic glycoside, along with 10 known compounds. Their structures were elucidated on the basis of spectroscopic data, including UV, IR, MS, and NMR experiments, along with chemical methods. At 10 µM, compounds 1 and 2 exhibited comparable activities with bicyclol in vitro assays for hepatoprotective activity against APAP-induced HepG2 cell damage.
Assuntos
Glicosídeos/isolamento & purificação , Hydrangea/química , Monoterpenos/isolamento & purificação , Caules de Planta/química , Compostos de Bifenilo/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Células Hep G2 , Humanos , Fígado/efeitos dos fármacos , Estrutura Molecular , Monoterpenos/química , Monoterpenos/farmacologia , Ressonância Magnética Nuclear BiomolecularRESUMO
Three new coumarin glycosides (1-3), together with three known compounds (4-6), have been obtained from the stems of Hydrangea paniculata Sieb. Their structures were elucidated based on spectroscopic data and chemical evidence. In addition, compounds 1-3 were screened for their neuroprotective effects against serum deprivation-induced PC12 cell damage, hepatoprotective activities against DL-galactosamine-induced toxicity in HL-7702 cells and their ability to inhibit LPS-induced nitric oxide production in the murine microglia BV2 cell line, but they were inactive.
Assuntos
Cumarínicos/isolamento & purificação , Glicosídeos/isolamento & purificação , Hydrangea/química , Fármacos Neuroprotetores/isolamento & purificação , Animais , Cumarínicos/química , Cumarínicos/farmacologia , Galactosamina/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Lipopolissacarídeos/farmacologia , Fígado/efeitos dos fármacos , Camundongos , Microglia/efeitos dos fármacos , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico/biossíntese , Células PC12 , Caules de Planta/química , RatosRESUMO
O-Methylmurrayamine A (7) and 7-methoxymurrayacine (8) are natural products isolated from Murraya koenigii and Murraya siamensis, respectively. In this paper, we report the synthesis of 7 and 8 which are featured in the key step of cyclization to form carbazole intermediate 5 with mild conditions. The structures were confirmed by 1H NMR, 13C NMR, and HR-ESI-MS. In addition, compounds 7 and 8 were tested for their neuroprotective effects against H2O2-induced PC12 cell damage. The results showed that compounds 7 and 8 have neuroprotective effect.
Assuntos
Carbazóis/síntese química , Carbazóis/farmacologia , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/farmacologia , Carbazóis/química , Humanos , Peróxido de Hidrogênio , Estrutura Molecular , Murraya/química , Fármacos Neuroprotetores/químicaRESUMO
A new phenylpropanoid glycoside (1), and two new coumarin glycosides (2, 3), together with two known compounds (4, 5), have been isolated from the stems of Hydrangea paniculata Sieb. Their structures have been determined by spectroscopic and chemical methods. Furthermore, compound 1 (50 µM) exhibited significant hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage in vitro assays.
Assuntos
Cumarínicos/química , Glicosídeos/química , Hydrangea/química , Propanóis/química , Substâncias Protetoras/química , Acetaminofen/antagonistas & inibidores , Acetaminofen/toxicidade , Antipiréticos/antagonistas & inibidores , Antipiréticos/toxicidade , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Células Hep G2 , Humanos , Estrutura Molecular , Caules de Planta/química , Propanóis/isolamento & purificação , Propanóis/farmacologia , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologia , Relação Estrutura-AtividadeRESUMO
We developed a limited proteolysis assay for estimating dynamics in plasma-borne protease activities using MALDI ToF MS analysis as readout. A highly specific limited proteolysis activity was elicited in human plasma by shifting the pH to 6. Mass spectrometry showed that two singly charged ion signals at m/z 2753.44 and m/z 2937.56 significantly increased in abundance under mild acidic conditions as a function of incubation time. For proving that a provoked proteolytic activity in mild acidic solution caused the appearance of the observed peptides, control measurements were performed (i) with pepstatin as protease inhibitor, (ii) with heat-denatured samples, (iii) at pH 1.7, and (iv) at pH 7.5. Mass spectrometric fragmentation analysis showed that the observed peptides encompass the amino acid sequences 1-24 and 1-26 from the N-terminus of human serum albumin. Investigations on peptidase specificities suggest that the two best candidates for the observed serum albumin cleavages are cathepsin D and E. Reproducibility, robustness, and sensitivity prove the potential of the developed limited proteolysis assay to become of clinical importance for estimating dynamics of plasma-borne proteases with respect to associated pathophysiological tissue conditions.
Assuntos
Plasma/metabolismo , Proteólise , Albumina Sérica/análise , Albumina Sérica/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Equilíbrio Ácido-Base , Sequência de Aminoácidos , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/metabolismo , Humanos , Dados de Sequência Molecular , Plasma/química , Estrutura Secundária de Proteína , Análise de Sequência de Proteína , Albumina Sérica/genéticaRESUMO
Five new coumarins, clauemarmarins I - M (1 - 4), together with 10 known analogs (5 - 14), were isolated from the stems of Clausena emarginata. Compounds 8 - 13 were obtained from this plant for the first time. Their structures were established and elucidated by comprehensive analysis of spectroscopic data. The absolute configurations of 1 - 4 were further determined by their electronic circular dichroism spectroscopy. Compounds 5, 7, 12, and 14 exhibited inhibitory effects on LPS-induced NO production. Compounds 5 - 7 showed selective neuroprotective effects in Aß25 - 35 model at 10 µm.
Assuntos
Clausena/química , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Caules de Planta/química , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/química , Relação Dose-Resposta a Droga , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Estrutura Molecular , Fármacos Neuroprotetores/química , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células PC12 , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/metabolismo , Ratos , Relação Estrutura-AtividadeRESUMO
Three new lignanosides (+)-(8S,7'S,8'S)-burselignan-9'-O-ß-d-glucopyrano side (1), (+)-(8R,7'S,8'R)-isolariciresinol-9'-O-ß-d-fucopyranoside (2), (-)-(8S, 7'R,8'R)-methoxyisoariciresinol-9'-O-α-l-rhamnoside (3), along with four known compounds, were isolated from the aerial parts of Lespedeza cuneata (Dum.Cours.) G.Don. The fucopyranoside has not been reported in this genus previously. Their structures and absolute configurations were elucidated on the basis of comprehensive spectroscopic analyses (UV, IR, HR-ESI-MS, 1D and 2D NMR, CD), as well as by comparison with known analogues in the literature. Compounds 2 and 6 showed moderate hepatoprotective activities.