RESUMEN
Fourteen previously undescribed diterpenoids, including an unusual diterpenoid (1) with a 9,10-seco-jatrophane skeleton, ten jatrophane-type diterpenoids (2-11), two lathyrane-type diterpenoids (12, 13), and an abietane-type diterpenoid (14), together with thirty-six known ones (15-50), were isolated from the whole plants of Euphorbia helioscopia L. The structures of the new isolates were characterized by spectroscopic methods, single-crystal X-ray diffraction analysis, and computational prediction of ECD and chemical shifts. Thirty-nine abundant diterpenoids were evaluated for their enhancement of NK cell-mediated killing of NSCLC cells. As a result, compounds 24, 33, and 41 were found to significantly enhance the killing activity of NK cells towards H1299-luci cells and A549-luci cells at the concentration of 2.5 µM.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Diterpenos/farmacología , Euphorbia/química , Células Asesinas Naturales/metabolismo , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Diterpenos/química , Diterpenos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Relación Estructura-ActividadRESUMEN
28-O-caffeoyl betulin (B-CA) has been demonstrated to reduce the cerebral infarct volume caused by transient middle cerebral artery occlusion (MCAO) injury. B-CA is a novel derivative of naturally occurring caffeoyl triterpene with little information associated with its pharmacological target(s). To date no data is available regarding the effect of B-CA on brain metabolism. In the present study, a 1H-NMR-based metabolomics approach was applied to investigate the therapeutic effects of B-CA on brain metabolism following MCAO in rats. Global metabolic profiles of the cortex in acute period (9 h after focal ischemia onset) after MCAO were compared between the groups (sham; MCAO + vehicle; MCAO + B-CA). MCAO induced several changes in the ipsilateral cortex of ischemic rats, which consequently led to the neuronal damage featured with the downregulation of NAA, including energy metabolism dysfunctions, oxidative stress, and neurotransmitter metabolism. Treatment with B-CA showed statistically significant rescue effects on the ischemic cortex of MCAO rats. Specifically, treatment with B-CA ameliorated the energy metabolism dysfunctions (back-regulating the levels of succinate, lactate, BCAAs, and carnitine), oxidative stress (upregulating the level of glutathione), and neurotransmitter metabolism disturbances (back-regulating the levels of γ-aminobutyric acid and acetylcholine) associated with the progression of ischemic stroke. With the administration of B-CA, the levels of three phospholipid related metabolites (O-phosphocholine, O-phosphoethanolamine, sn-glycero-3-phosphocholine) and NAA improved significantly. Overall, our findings suggest that treatment with B-CA may provide neuroprotection by augmenting the metabolic changes observed in the cortex following MCAO in rats.
Asunto(s)
Corteza Cerebral/metabolismo , Infarto de la Arteria Cerebral Media/metabolismo , Enfermedades Metabólicas/metabolismo , Metaboloma/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Triterpenos/uso terapéutico , Animales , Corteza Cerebral/efectos de los fármacos , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Masculino , Enfermedades Metabólicas/tratamiento farmacológico , Metabolómica , Espectroscopía de Protones por Resonancia Magnética , Curva ROC , Ratas Sprague-DawleyRESUMEN
Three new triterpenoids, celastrusins A-C (1-3), together with 3-O-caffeoyl-α-amyrin (4) were isolated from the root bark of Celastrus orbiculatus. Their structures were identified by spectroscopic analysis, X-ray crystallography using Cu Kα radiation, and the comparison of both observed and reported spectroscopic data. An in vitro bioassay revealed that the caffeoyl triterpenoid esters 1, 3, and 4 possess neuroprotective effects against oxygen-glucose deprivation (OGD) induced SH-SY5Y cell damage. Further animal studies indicated that compound 1 significantly reduced brain infarction after transient middle cerebral artery occlusion (MCAO) in rats using a 10 mg/kg (i.v.) dose.
Asunto(s)
Ácidos Cafeicos/aislamiento & purificación , Ácidos Cafeicos/farmacología , Celastrus/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Isquemia/tratamiento farmacológico , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Fármacos Neuroprotectores/farmacología , Triterpenos/aislamiento & purificación , Triterpenos/farmacología , Animales , Ácidos Cafeicos/química , Enfermedades Arteriales Cerebrales/tratamiento farmacológico , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/química , Ésteres , Humanos , Masculino , Conformación Molecular , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Ácido Oleanólico/análogos & derivados , Corteza de la Planta/química , Raíces de Plantas/química , Ratas , Triterpenos/químicaRESUMEN
Three new chalcones, xanthoangelols K-M (1-3), together with 19 known compounds were isolated from the stems of Angelica keiskei Koidzumi, a well-known rejuvenated and anti-diabetic plant originated from Japan. The structures of compounds 1-3 were elucidated on the basis of spectroscopic data and Mosher's method. All compounds were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Among them, six chalcones, xanthoangelol K (1), xanthoangelol (4), xanthoangelol F (5), 4-hydroxyderricin (6), xanthoangelol D (7), xanthoangelol E (8), and a coumarin, methoxsalen (17), showed strong PTP1B inhibitory effect with IC50 values of 0.82, 1.97, 1.67, 2.47, 3.97, 1.43, and 2.53µg/mL, respectively. A kinetic study revealed that compound 1 inhibited PTP1B with characteristics typical of a competitive inhibitor. Molecular docking simulations elucidated that ring B of 1 may anchor in a pocket of PTP1B and the molecule is stabilized by hydrogen bonds with Arg47, Asp48, and π-π interaction with Phe182 of PTP1B.
Asunto(s)
Angelica/química , Chalconas/aislamiento & purificación , Tallos de la Planta/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Chalconas/química , Chalconas/metabolismo , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/metabolismo , Enlace de Hidrógeno , Concentración 50 Inhibidora , Japón , Modelos Moleculares , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismoRESUMEN
Chemical investigation of the cupules of Lithocarpus polystachyus resulted in the identification of four 3,4-seco-homo-cycloartane and one homo-cycloartane derivatives named lithocarpic acids O-S. Their structures were determined based on extensive 1D/2D NMR, IR, MS spectroscopic analyses and chemical methods. Lithocarpic acid O (1) exhibited inhibitory activities on mouse and human isozymes of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) with IC50 values of 0.49 and 1.1 µM, respectively.
Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/uso terapéutico , Fagaceae/química , Extractos Vegetales/uso terapéutico , Triterpenos/química , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/farmacología , Animales , Medicamentos Herbarios Chinos , Humanos , Ratones , Estructura Molecular , Fitoterapia , Extractos Vegetales/farmacologíaRESUMEN
Four new triterpenoids, 2-O-acetyl-3-O-(4'-O-acetyl)-α-l-arabinopyranosylmaslinic acid (1), 2-O-acetyl-3-O-(3'-O-acetyl)-α-l-arabinopyranosylmaslinic acid (2), 2-O-acetyl-3-O-(3',4'-O-diacetyl)-α-l-arabinopyranosylmaslinic acid (3), and 3-O-(3'-O-acetyl)-α-l-arabinopyranosyloleanolic acid (4), together with six known triterpenoids, 3-O-(4'-O-acetyl)-α-l-arabinopyranosyloleanolic acid (5), maslinic acid (6), 2-O-acetylmaslinic acid (7), 3-O-acetylmaslinic acid (8), betulinic acid (9), and 2α-hydroxy-3ß-O-acetylbetulinic acid (10), were isolated from the EtOAc extract of Garcinia hanburyi resin. Their structures were elucidated by analysis of the spectroscopic data and chemical methods.
Asunto(s)
Garcinia/química , Triterpenos/aislamiento & purificación , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Triterpenos Pentacíclicos , Resinas de Plantas/química , Triterpenos/química , Vietnam , Ácido BetulínicoRESUMEN
AIM: The aim of this study was to determine the therapeutic effect of Periplocoside A (PSA), a natural product isolated from the traditional Chinese herbal medicine Periploca sepium Bge, in MOG(35-55) (myelin oligodendrocyte glycoprotein 35-55)-induced experimental autoimmune encephalomyelitis (EAE). METHODS: Female C57BL/6 mice immunized with MOG(35-55) were treated with (50 mg/kg or 25 mg/kg) or without PSA following immunization and continuously throughout the study. The degree of CNS inflammation was evaluated by H&E staining. Anti-MOG-specific recall responses were analyzed by [3H]-Thymidine incorporation, ELISA, and RT-PCR. The proportion of IL-17-producing T cells was measured by flow cytometry. RESULTS: Oral administration of PSA significantly reduced the incidence and severity of EAE, which closely paralleled the inhibition of MOG(35-55)-specific IL-17 production. Importantly, PSA inhibited the transcription of IL-17 mRNA and RORgammat. Further studies examining intracellular staining and adoptive transfer EAE validated the direct suppressive effect of PSA on Th17 cells. In vitro studies also showed that PSA significantly inhibited the differentiation of Th17 cells from murine purified CD4+ T cells in a dose-dependent manner. CONCLUSION: PSA ameliorated EAE by suppressing IL-17 production and inhibited the differentiation of Th17 cells in vitro. Our results provide new insight into the potential mechanisms underlying the immunosuppressive and anti-inflammatory effects of PSA.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Encefalomielitis Autoinmune Experimental/prevención & control , Glicósidos/uso terapéutico , Interleucina-17/inmunología , Pregnenos/uso terapéutico , Linfocitos T/efectos de los fármacos , Animales , Diferenciación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/aislamiento & purificación , Encefalomielitis Autoinmune Experimental/inducido químicamente , Encefalomielitis Autoinmune Experimental/inmunología , Femenino , Glicoproteínas , Glicósidos/aislamiento & purificación , Ratones , Ratones Endogámicos C57BL , Glicoproteína Mielina-Oligodendrócito , Fragmentos de Péptidos , Periploca/química , Pregnenos/aislamiento & purificación , Médula Espinal/efectos de los fármacos , Médula Espinal/inmunología , Linfocitos T/inmunologíaRESUMEN
Two new dihydrochalcone glycosides named 6''-O-acetyltrilobatin (1) and 3''-O-acetylphloridzin (2) as well as four known compounds were isolated from the leaves of Lithocarpus litseifolius (Hance) Chun (family Fagaceae). Their structures were elucidated on the basis of spectroscopic analyses. The phenomena of C-H --> C-D exchange were observed in NMR spectra of the isolated phenolic components when measured in deuterated methanol.
Asunto(s)
Chalconas/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Fagaceae/química , Glicósidos/aislamiento & purificación , Resonancia Magnética Nuclear Biomolecular , Chalconas/química , Medicamentos Herbarios Chinos/química , Glicósidos/química , Estructura Molecular , Hojas de la Planta/químicaRESUMEN
Periploca sepium Bge, a traditional Chinese herb medicine, is widely used for treating rheumatoid arthritis in china. Periplocoside A (PSA), a pregnane glycoside, is a new nature product compound isolated from P. sepium Bge. We examined the protective effects of PSA, on concanavaline A (ConA)-induced hepatitis. Pretreatment with PSA dramatically ameliorated ConA-induced liver injury, which was characterized by reducing serum alanine transaminase (ALT), pathogenic cytokines of interleukin (IL)-4 and interferon (IFN)-gamma levels, impeding the liver necrosis, and thus elevating the survival rate. In vitro, PSA inhibited IL-4 and IFN-gamma productions of alpha-galactosylceramide (alpha-GalCer) or anti-CD3-activated Natural killer T (NKT) cells. Enzyme Linked Immunosorbent Assay (ELISA) and Reverse Transcription Polymerase Chain Reaction (RT-PCR) assays revealed PSA suppressed IL-4 transcription and IFN-gamma translation. In conclusion, PSA had significantly preventative effect on ConA-induced hepatitis, which was closely associated with inhibition of NKT-derived inflammatory cytokine productions. These findings suggested that PSA has the therapeutic potential for treatment of human autoimmune-related hepatitis.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Concanavalina A/antagonistas & inhibidores , Concanavalina A/toxicidad , Citocinas/biosíntesis , Glicósidos/farmacología , Células Asesinas Naturales/metabolismo , Periploca/química , Pregnenos/farmacología , Alanina Transaminasa/sangre , Animales , Complejo CD3/farmacología , Proliferación Celular/efectos de los fármacos , Separación Celular , Supervivencia Celular/efectos de los fármacos , Citocinas/fisiología , Femenino , Citometría de Flujo , Galactosilceramidas/farmacología , Indicadores y Reactivos , Pruebas de Función Hepática , Prueba de Cultivo Mixto de Linfocitos , Linfocitos/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Oligosacáridos/farmacologíaRESUMEN
OBJECTIVE: To study on the protective effects of new compound codonopsis tablets against acute mountain sickness (AMS). METHODS: Forty-five male plain resident soldiers stayed at 1400 m altitude for 3 months were randomly divided into two groups, control (15 men) and treatment group (30 men). Single blind trial was used in this study. The subjects in the two groups took placebo and new compound codonopsis tablets respectively for 5 days before climbing to high mountain, and continued to take for another 10 days until the 3rd day after arriving at 5200 m altitude. On the 1st , 3rd, and 5th day after they arrived at 5200 m altitude, the score and the degree of AMS symptoms of soldiers were followed up and recorded according to State Military Standard GJB1098-91--"Principles of diagnosis and treatment of benign form of acute mountain sickness", heart rate (beats/min) and arterial oxygen saturation (%) were detenrmined. On the 6th day after they arrived at high altitude, forced vital capacity(FVC), forced expired volume in one second(FEV1.0), FEV1% (FEV1.0/FVC), FEF25%-75%, peak expiratory flow (PEF) and maximal voluntary ventilation (MVV) were detected, total frequency of hands cross movement and memory of order numbers test were measured. RESULTS: Comparison with control, AMS symptoms of treatment group reduced on the 1st, 3rd, and 5th day after arriving at 5200 m high altitude (P < 0.01). The degree of AMS symptoms of treatment group was significantly different from that of control. The proportion of slight symptoms in treatment group was high, and that of relative serious symptoms in control was high. Compared with control, FVC, FEV1.0, FEF25%-75%, PEF and MVV of treatment group increased (P < 0.05, P < 0.01), and Ttis, Ctis of treatment group increased (P < 0.05, P < 0.01), Atime decreased markedly (P < 0.05), there was no statistically significant difference in Etis and Sum between the two groups. CONCLUSION: New compound codonopsis tablets could decrease the incidence of AMS, mitigate the symptoms of AMS, and improve breathing function and fingers movement function. New compound codonopsis tablets have an obvious effect on prevention and treatment of acute mountain sickness.
Asunto(s)
Mal de Altura/prevención & control , Codonopsis/química , Medicamentos Herbarios Chinos/uso terapéutico , Fitoterapia , Enfermedad Aguda , Adolescente , Composición de Medicamentos , Humanos , Masculino , Comprimidos , Adulto JovenRESUMEN
Chlorogenic acid and its related compounds are abundant plant polyphenols that have a diverse antiviral activity. In this study, HepG2.2.15 cells and duck hepatitis B virus infection model were used as in vitro and in vivo models to evaluate their anti-HBV activity. In the cell model, all the three compounds inhibited HBV-DNA replication as well as HBsAg production. Chlorogenic acid and caffeic acid also reduced serum DHBV level in DHBV-infected duckling model. Moreover, the anti-HBV activity of crude extracts of coffee beans, which have a high content of chlorogenic acid, was studied. Both the extracts of regular coffee and that of decaffeinated coffee showed inhibitory effect on HBV replication.