RESUMEN
Lysidrhodosides A-I (1-9), nine acylphloroglucinol glucoside derivatives along with three known analogues (10-12) were isolated from the leaves of Lysidice rhodostegia. Their structures and absolute configuration were elucidated by spectroscopic data analysis (NMR, UV, IR, HR-ESI-MS), single-crystal X-ray diffraction, and acid hydrolysis with HPLC analysis. Notably, compounds 7-9 represent the first examples of 3-methylbutyryl phloroglucinol glucoside dimers isolated from this plant. Additionally, compounds 1-12 were assessed for their inhibitory effects on nitric oxide (NO) in the LPS-induced BV-2 cells. The results showed that compounds 6 and 12 significantly inhibited the production of the inflammatory mediator NO, with an inhibitory rate of 95.96 and 91.13% at a concentration of 50 µM, respectively.
Asunto(s)
Fabaceae , Glucósidos , Glucósidos/farmacología , Estructura Molecular , Floroglucinol/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Espectroscopía de Resonancia Magnética , Fabaceae/química , Óxido NítricoRESUMEN
Two new clerodane diterpenoids (1 and 2), a new pyran-2-one derivative (3), along with five known compounds (4â8), were isolated from Croton crassifolius. Notably, crassifolin X (1) is a novel clerodane diterpenoid, characterized with a peculiar δ-lactone core being formed between C-1 and C-4. Their structures, including absolute configurations, were established on the basis of spectroscopic methods (UV, IR, HRESIMS and NMR), and circular dichroism experiments. In addition, all compounds were evaluated for their anti-neuroinflammatory activities based on the expression of TNF-α and IL-6 levels on LPS-induced BV2 cells, and compounds 1â3 and 5 showed potential anti-neuroinflammatory activity.
Asunto(s)
Croton , Diterpenos de Tipo Clerodano , Diterpenos , Croton/química , Diterpenos/química , Diterpenos de Tipo Clerodano/química , Diterpenos de Tipo Clerodano/farmacología , Estructura Molecular , Raíces de Plantas/química , Piranos/análisisRESUMEN
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.
Asunto(s)
Antioxidantes/farmacología , Fabaceae/química , Glicósidos/farmacología , Polifenoles/farmacología , Estilbenos/farmacología , Antioxidantes/aislamiento & purificación , China , Glicósidos/aislamiento & purificación , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Raíces de Plantas/química , Polifenoles/aislamiento & purificación , Estilbenos/aislamiento & purificaciónRESUMEN
Five matrine-type alkaloids (1â5) including two new compounds (1 and 3) and a new natural product (2) were isolated from the roots of Sophora tonkinesis. Their structures were identified by extensive spectroscopic analysis (UV, IR, HRESIMS and NMR). The absolute configurations of 2 and 3 were determined by X-ray diffraction. Compounds 1â5 were evaluated their activity against inflammatory cytokines TNF-α and IL-6 levels on LPS-induced RAW 264.7 macrophages, and compound 1 showed the most significant activity, potent than that of matrine, the representative ingredient from Sophora plants.
Asunto(s)
Alcaloides/farmacología , Antiinflamatorios/química , Quinolizinas/farmacología , Sophora/química , Alcaloides/química , Animales , China , Espectroscopía de Resonancia Magnética , Ratones , Estructura Molecular , Raíces de Plantas/química , Células RAW 264.7 , MatrinasRESUMEN
Two new isoquinoline alkaloids, 6 R,6aS-N-nantenine Nß-oxide (1), 6S,6aS-N-nantenine Nα-oxide (2), along with nine known alkaloids, nantenine (3), oxonantenine (4), protopine (5), nornantenine (6), N-methyl-laurotetanine (7), isocorydine (8), O-methyflavinantine (9), N-methyl-2,3,6-trimethoxymorphinan-dien-7-one Nß-oxide (10) and (+)-10-O-methylhernovine Nß-oxide (11) were isolated from the seeds of Nandina domestica. Their structures were elucidated by extensive analyses of spectroscopic data (IR, UV, HRESIMS, 1 D and 2 D NMR), ECD calculation and comparison with the related literatures. In addition, the cytotoxicity against A549 cells of these alkaloids was determined by the MTT assay.
Asunto(s)
Alcaloides , Berberidaceae , Isoquinolinas/farmacología , Células A549 , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Berberidaceae/química , Humanos , Isoquinolinas/aislamiento & purificación , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Extractos Vegetales , Semillas/químicaRESUMEN
Pegaharines A-G (1-6), six novel ß-carboline alkaloids representing three types of skeleton, were isolated from the seeds of Peganum harmala. Compound 1 is a peculiar ß-carboline alkaloid characterized by the unprecedented carbon skeleton of an azepine-indole system. Compounds 3-6 represent the first examples of heterodimers constructed from rare tetracyclic ß-carboline and classic tricyclic ß-carboline alkaloids. Compounds 1 and 2 were characterized by X-ray crystallography. Compound 4 exhibited strong antiviral activity against HSV-2, with an IC50 value of 2.12 ± 0.14 µM.
Asunto(s)
Alcaloides/química , Antivirales/farmacología , Carbolinas/química , Herpesvirus Humano 2/efectos de los fármacos , Peganum/química , Extractos Vegetales/química , Antivirales/química , Herpesvirus Humano 2/química , Estructura Molecular , Semillas/químicaRESUMEN
A new aromatic glycoside (1) and a new natural product, neolignan (2), along with twenty-three known compounds (3-25), were isolated from the thorns of Gleditsia sinensis. According to the spectroscopic analyses (IR, UV, HRESIMS, NMR and ECD), the structures of isolates were elucidated. Herein, compounds 4, 6-8, 10-13, 15, 16, 18, 20, 23 were isolated from the plant of G. sinensis for the first time. Moreover, compounds 4, 6, 15 and 24 showed cytotoxic effects on human ovarian cancer (SKOV-3) cells with IC50 values of 24.83 ± 4.90, 48.86 ± 9.11, 80.13 ± 5.62, 15.38 ± 2.21 µM, respectively. [Formula: see text].
Asunto(s)
Antineoplásicos , Gleditsia , Glicósidos/farmacología , Humanos , Estructura Molecular , Extractos VegetalesRESUMEN
Two new quinolizidine-based alkaloids (2 and 12), along with ten known ones (1, 3-11) were isolated from the roots of S. tonkinensis. Their structures were determined by spectroscopic data (including NMR, MS, IR, and UV), X-ray single crystal diffraction, electronic circular dichroism analyses (ECD), and comparing with related literatures. Compounds 1, 3-12 at non-toxic concentrations exhibited potent anti-inflammatory activities according to in vitro and in vivo anti-inflammatory tests. Among them, (-)-anagyrine (4), sophocarpine (8), 14ß-hydroxymatrine (10), and 7ß-sophoramine (12) showed more potent in vitro anti-inflammatory activities, and 5α,14ß-dihydroxymatrine (2), (-)-anagyrine (4), sophocarpine (8), and 5α-hydroxymatrine (9) exhibited better in vivo anti-inflammatory effects.
Asunto(s)
Alcaloides/farmacología , Antiinflamatorios/farmacología , Quinolizidinas/farmacología , Sophora/química , Alcaloides/aislamiento & purificación , Animales , Animales Modificados Genéticamente , Antiinflamatorios/aislamiento & purificación , Azocinas , China , Ratones , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Raíces de Plantas/química , Quinolizidinas/aislamiento & purificación , Quinolizinas , Células RAW 264.7 , Pez CebraRESUMEN
Two new oleanane-type triterpenoids (1-2), a new ursane-type triterpenoid (3), and a new podocarpane-type diterpenoid (4), together with 20 known compounds (5-24) were isolated from the stems of Celastrus hindsii Benth. Their structures were identified on the basis of the spectral data (HRESIMS, IR, UV, 1D, and 2D NMR) and the absolute configurations were determined by comparison of experimental and calculated ECD data. The structures of 1 and 4 were further confirmed by single crystal X-ray diffraction analysis. In addition, all compounds were evaluated for their in vitro antiviral activities against respiratory syncytium virus (RSV) using cytopathic effect (CPE) reduction assay. Compounds 7, 10, 11, 19 and 24 exhibited obvious anti-RSV activity with IC50 values from 1.55 to 6.25⯵M.
Asunto(s)
Antivirales/farmacología , Celastrus/química , Ácido Oleanólico/farmacología , Virus Sincitial Respiratorio Humano/efectos de los fármacos , Antivirales/aislamiento & purificación , China , Estructura Molecular , Ácido Oleanólico/aislamiento & purificación , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Tallos de la Planta/químicaRESUMEN
Estrogen-stimulating principles have been demonstrated to relieve postmenopausal syndrome effectively. Gardenia jasminoides Ellis (GJE) is an herbal medicine possessing multiple pharmacological effects on human health with low toxicity. However, the therapeutic effects of GJE on the management of postmenopausal syndrome and its mechanism of action have not been fully elucidated. In this study, network pharmacology-based approaches were employed to examine steroidogenesis under the influence of GJE. In addition, the possibility of toxicity of GJE was ruled out and four probable active compounds were predicted. In parallel, a chromatographic fraction of GJE with estrogen-stimulating effect was identified and nine major compounds were isolated from this active fraction. Among the nine compounds, four of them were identified by network pharmacology, validating the use of network pharmacology to predict active compounds. Then the phenotypic approaches were utilized to verify that rutin, chlorogenic acid (CGA) and geniposidic acid (GA) exerted an estrogen-stimulating effect on ovarian granulosa cells. Furthermore, the results of target-based approaches indicated that rutin, CGA, and GA could up-regulate the FSHR-aromatase pathway in ovarian granulosa cells. The stimulation of estrogen production by rat ovarian granulosa cells under the influence of the three compounds underwent a decline when the follicle-stimulating hormone receptor (FSHR) was blocked by antibodies against the receptor, indicating the involvement of FSHR in the estradiol-stimulating activity of the three compounds. The effects of the three compounds on estrogen biosynthesis- related gene expression level were further confirmed by Western blot assay. Importantly, the MTT results showed that exposure of breast cancer cells to the three compounds resulted in reduction of cell viability, demonstrating the cytotoxicity of the three compounds. Collectively, rutin, chlorogenic acid and geniposidic acid may contribute to the therapeutic potential of GJE for the treatment of postmenopausal syndrome.
RESUMEN
Respiratory syncytial virus (RSV) is one of the most common respiratory pathogens. Immoderate inflammation plays a great role in causing RSV-induced diseases. In the present study, watsonianone A, isolated from the fruit of Rhodomyrtus tomentosa (Ait.) Hassk, was found to show a good inhibitory effect on RSV-induced NO production, with a half-maximal inhibitory concentration of 37.2 ± 1.6 µM. Enzyme-linked immunosorbent assay and fluorescence quantitative polymerase chain reaction analyses indicated that watsonianone A markedly reduced both mRNA and protein levels of tumor necrosis factor α, interleukin 6, and monocyte chemoattractant protein 1 in RSV-infected RAW264.7 cells. Mechanistically, watsonianone A inhibited nuclear factor κB (NF-κB) activation by suppressing IκBα phosphorylation. Further analysis revealed that watsonianone A activated the thioredoxin system and decreased intracellular reactive oxygen species (ROS) levels, which are closely associated with NF-κB activation in RSV-infected cells. These results reveal that watsonianone A can attenuate RSV-induced inflammation via the suppression of ROS-sensitive inflammatory signaling.
Asunto(s)
Ciclohexanonas/farmacología , Frutas/química , Myrtaceae/química , Extractos Vegetales/farmacología , Infecciones por Virus Sincitial Respiratorio/inmunología , Virus Sincitiales Respiratorios/efectos de los fármacos , Humanos , Proteínas I-kappa B/genética , Proteínas I-kappa B/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , FN-kappa B/genética , FN-kappa B/inmunología , Especies Reactivas de Oxígeno/inmunología , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitiales Respiratorios/fisiología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Six new acylphloroglucinols (1 - 6) were isolated from Dryopteris championii. Their structures were established on the basis of extensive analysis of spectroscopic data and comparison with reported data. The antibacterial activities of the isolates were evaluated against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Dickeya zeae.
Asunto(s)
Antibacterianos/aislamiento & purificación , Dryopteris/química , Floroglucinol/aislamiento & purificación , Antibacterianos/química , Bacterias/efectos de los fármacos , Estructura Molecular , Floroglucinol/química , Floroglucinol/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Análisis EspectralRESUMEN
Seven sesquiterpene lactones, 8-O-methacryloylelephanpane, 2,4-bis-O-methyl-8-O-methacryloylelephanpane, 4-O-ethyl-8-O-methacryloylelephanpane, 8-O-methacryloylisoelephanpane, 2-O-demethyltomenphantopin C, molephantin A, molephantin B, along with ten known ones, were isolated from Elephantopus mollis (Asteraceae). Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HRESIMS, 1D and 2D NMR). The isolates were evaluated for their anti-inflammatory activities on LPS-stimulated RAW 264.7 cells, and all tested compounds exhibited potent anti-inflammatory effects with IC50 values of 0.57 ± 0.17 to 14.34 ± 1.61 µM, except that compound tomenphantopin C exhibited moderate anti-inflammatory activity with IC50 values of 59.97 ± 1.53 µM.
Asunto(s)
Antiinflamatorios/química , Asteraceae/química , Sesquiterpenos/química , Animales , Antiinflamatorios/aislamiento & purificación , Ratones , Estructura Molecular , Extractos Vegetales/química , Células RAW 264.7 , Sesquiterpenos/aislamiento & purificaciónRESUMEN
Five new diterpenoid alkaloids, ajacisines A-E (1-5), were isolated from Delphinium ajacis, along with seven known alkaloids (6-12). On the basis of their spectral data (IR, UV, HR-ESI-MS, 1D and 2D NMR) and chemical properties, the structures of compounds 1-12 were identified. All isolated compounds were evaluated for their in vitro antiviral activities against respiratory syncytial virus, and compounds 3-5 and 8 exhibited moderate to weak effects with IC50 values of 75.2 ± 1.1, 35.1 ± 0.6, 10.1 ± 0.3, and 50.2 ± 0.5 µM, respectively.
Asunto(s)
Alcaloides/farmacología , Antivirales/farmacología , Delphinium/química , Diterpenos/farmacología , Estructura Molecular , Virus Sincitial Respiratorio Humano/efectos de los fármacos , Alcaloides/química , Alcaloides/aislamiento & purificación , Antivirales/química , Antivirales/aislamiento & purificación , Línea Celular Tumoral , Diterpenos/química , Diterpenos/aislamiento & purificación , Humanos , Espectroscopía de Resonancia Magnética , Raíces de Plantas/química , Tallos de la Planta/químicaRESUMEN
Six unusual matrine-type alkaloid dimers, flavesines A-F (1-6, respectively), together with three proposed biosynthetic intermediates (7-9) were isolated from the roots of Sophora flavescens. Compounds 1-5 were the first natural matrine-type alkaloid dimers, and compound 6 represented an unprecedented dimerization pattern constructed by matrine and (-)-cytisine. Their structures were elucidated by NMR, MS, single-crystal X-ray diffraction, and a chemical method. The hypothetical biogenetic pathways of 1-6 were also proposed. Compounds 1-9 exhibited inhibitory activities against hepatitis B virus.
Asunto(s)
Alcaloides/química , Virus de la Hepatitis B/efectos de los fármacos , Quinolizinas/química , Sophora/química , Alcaloides/farmacología , Carbono/química , Dimerización , Células Hep G2 , Humanos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/farmacología , Raíces de Plantas/química , Quinolizinas/farmacología , Reacción en Cadena en Tiempo Real de la Polimerasa , Espectrofotometría , Difracción de Rayos X , MatrinasRESUMEN
Three new ring B-seco limonoids, ciliatonoids A-C (1-3), were isolated from Toona ciliate and structurally characterized by spectroscopic data, X-ray crystallography, and electronic circular dichroism analysis. Ciliatonoids A and B feature an unprecedented limonoid architecture, while ciliatonoid C belongs to a rare class of limonoids. Biological evaluation showed that compound 3 exhibited modest activities against the tested tumor cell lines.
Asunto(s)
Antineoplásicos Fitogénicos/química , Limoninas/química , Meliaceae/química , Extractos Vegetales/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Dicroismo Circular , Cristalografía por Rayos X , Humanos , Limoninas/aislamiento & purificación , Limoninas/farmacología , Espectroscopía de Resonancia Magnética/métodos , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacologíaRESUMEN
Sesquiterpene lactones (SLs) are the active constituents of a variety of medicinal plants and found to have potential anticancer activities. However, the intracellular molecular targets of SLs and the underlying molecular mechanisms have not been well elucidated. In this study, we observed that EM23, a natural SL, exhibited anti-cancer activity in human cervical cancer cell lines by inducing apoptosis as indicated by caspase 3 activation, XIAP downregulation and mitochondrial dysfunction. Mechanistic studies indicated that EM23-induced apoptosis was mediated by reactive oxygen species (ROS) and the knockdown of thioredoxin (Trx) or thioredoxin reductase (TrxR) resulted in a reduction in apoptosis. EM23 attenuated TrxR activity by alkylation of C-terminal redox-active site Sec498 of TrxR and inhibited the expression levels of Trx/TrxR to facilitate ROS accumulation. Furthermore, inhibition of Trx/TrxR system resulted in the dissociation of ASK1 from Trx and the downstream activation of JNK. Pretreatment with ASK1/JNK inhibitors partially rescued cells from EM23-induced apoptosis. Additionally, EM23 inhibited Akt/mTOR pathway and induced autophagy, which was observed to be proapoptotic and mediated by ROS. Together, these results reveal a potential molecular mechanism for the apoptotic induction observed with SL compound EM23, and emphasize its putative role as a therapeutic agent for human cervical cancer.
Asunto(s)
Lactonas/farmacología , MAP Quinasa Quinasa 4/metabolismo , Sesquiterpenos/farmacología , Reductasa de Tiorredoxina-Disulfuro/antagonistas & inhibidores , Reductasa de Tiorredoxina-Disulfuro/metabolismo , Neoplasias del Cuello Uterino/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Activación Enzimática , Femenino , Células HL-60 , Humanos , Células K562 , Células MCF-7 , Especies Reactivas de Oxígeno/metabolismo , Transfección , Neoplasias del Cuello Uterino/enzimología , Neoplasias del Cuello Uterino/patologíaRESUMEN
Four limonoids, cipacinoids A-D (1-4), with spirocyclic skeletons were isolated from Cipadessa cinerascens. It is particularly notable that compounds 1-3 had a 17S-configuration for the first time in the limonoid family. Their structures with absolute configurations were assigned by spectroscopic data, X-ray crystallography, and CD analysis. Compound 1 showed moderate protein tyrosine phosphatase 1B (PTP1B) inhibition.
Asunto(s)
Medicamentos Herbarios Chinos/aislamiento & purificación , Limoninas/aislamiento & purificación , Meliaceae/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Compuestos de Espiro/aislamiento & purificación , Dicroismo Circular , Cristalografía por Rayos X , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Limoninas/química , Limoninas/farmacología , Conformación Molecular , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Hojas de la Planta/química , Compuestos de Espiro/química , Compuestos de Espiro/farmacologíaRESUMEN
Chinese medicine is known to treat complex diseases with multiple components and multiple targets. However, the main effective components and their related key targets and functions remain to be identified. Herein, a network analysis method was developed to identify the main effective components and key targets of a Chinese medicine, Lianhua-Qingwen Formula (LQF). The LQF is commonly used for the prevention and treatment of viral influenza in China. It is composed of 11 herbs, gypsum and menthol with 61 compounds being identified in our previous work. In this paper, these 61 candidate compounds were used to find their related targets and construct the predicted-target (PT) network. An influenza-related protein-protein interaction (PPI) network was constructed and integrated with the PT network. Then the compound-effective target (CET) network and compound-ineffective target network (CIT) were extracted, respectively. A novel approach was developed to identify effective components by comparing CET and CIT networks. As a result, 15 main effective components were identified along with 61 corresponding targets. 7 of these main effective components were further experimentally validated to have antivirus efficacy in vitro. The main effective component-target (MECT) network was further constructed with main effective components and their key targets. Gene Ontology (GO) analysis of the MECT network predicted key functions such as NO production being modulated by the LQF. Interestingly, five effective components were experimentally tested and exhibited inhibitory effects on NO production in the LPS induced RAW 264.7 cell. In summary, we have developed a novel approach to identify the main effective components in a Chinese medicine LQF and experimentally validated some of the predictions.
Asunto(s)
Antivirales/química , Medicamentos Herbarios Chinos/química , Algoritmos , Animales , Antivirales/farmacología , Evaluación Preclínica de Medicamentos , Medicamentos Herbarios Chinos/farmacología , Ontología de Genes , Redes Reguladoras de Genes , Humanos , Gripe Humana/tratamiento farmacológico , Concentración 50 Inhibidora , Lipopolisacáridos/farmacología , Ratones , Óxido Nítrico/biosíntesis , Mapas de Interacción de Proteínas , Células RAW 264.7RESUMEN
Objective: To investigate the chemical constituents of Thalictrum fortunei. Methods: Compounds were separated and purified by chromatographic methods and the structures were identified by their physicochemical properties and spectroscopic data. Results: Ten compounds were isolated and identified as bergenin( 1),1-( 4-hydroxy-3-methoxy)-phenyl-2-[4-( 1,2,3-trihydroxypropyl)-2-methoxy]-phenoxym-1,3-propandiol( 2) ã4-( 2-hydroxyethyl)-2-methoxyphenyl-O-ß-D-glucopyranoside( 3),meliasendanin D( 4),2-( 4-hydroxy-3-methoxyphenyl)-ethyl-O-ß-D-glucopyranoside( 5),kizutasaponin C( 6),2-( 3-hydroxy-4-methoxyphenyl)-ethyl-O-ß-Dglucopyranoside( 7),ß-sitosterol( 8),3-O-ß-D-glucopyranosyl( 1â6)-ß-D-glucopyranosyl( 22 S,24Z)-cycloart-24-en-3ß,22,30-tetraol-26-O-ß-D-glucopyranoside( 9) and 3-O-ß-D-quinovopyranosyl( 1â6)-ß-D-glucopyranosyl( 1â4)-ß-D-fucopyranosyl( 22 S,24Z)-cycloart-24-en-3ß,22,26-triaol-26-O-ß-D-glucopyranoside( 10). Conclusion: Compounds 1 ~ 6 are isolated form this plant for the first time.