RESUMO
Twelve new ent-abietane diterpenoids, chlorabietins A-L (), were isolated from the roots of Chloranthus oldhamii. Their structures and absolute configurations were determined by extensive spectroscopic analyses, X-ray diffraction, and experimental/calculated electronic circular dichroism (ECD) spectroscopy. Among the new isolates, chlorabietins D () and E () are the first two naturally occurring 8-spiro-fused 9,10-seco-ent-abietanes containing an unexpected cis-fused A/B ring system. Chlorabietin F () is a rare chinane-type diterpenoid featuring a hitherto unknown C-ring cleavage between C-13 and C-14, which might be derived from a common precursor of the above spiro-diterpenoid epimers and , and their biosynthetic relationships are briefly discussed. Meanwhile, chlorabietin I () is the first representative of the abietane-type diterpenoids possessing a tetrahydrofurano function bridging C-6 and C-19. Chlorabietins B (), C (), F (), and G () showed anti-neuroinflammatory effects by inhibiting the nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine BV-2 microglial cells, with IC50 values ranging from 16.4 to 33.8 µM.
Assuntos
Abietanos/química , Abietanos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Magnoliopsida/química , Microglia/efeitos dos fármacos , Animais , Linhagem Celular , Camundongos , Microglia/metabolismo , Modelos Moleculares , Conformação Molecular , Óxido Nítrico/biossíntese , Raízes de Plantas/químicaRESUMO
Nine unexpected new flavonol glycoside cyclodimers in the truxinate (1-7, biginkgosides A-G, respectively) or truxillate [biginkgosides H (8) and I (9)] forms were isolated as minor components from the extract of Ginkgo biloba leaves. The new dimers possess an unusual cyclobutane ring formed by a [2+2]-cycloaddition between two symmetric (for compounds 1-5 and 7-9) or nonsymmetric (for 6) flavonol coumaroyl glucorhamnosides. A plausible biosynthetic pathway for these new compounds based on the frontier molecular orbital theory of cycloaddition reactions is briefly discussed. An antineuroinflammatory screening revealed that biginkgosides E (5) and H (8) inhibited nitric oxide production in lipopolysaccharide-activated BV-2 microglial cells, with IC50 values of 2.91 and 17.23 µM, respectively. Additionally, biginkgoside F (6) showed a significant neuroprotective effect (34.3% increase in cell viability at 1 µM) against Aß25-35-induced cell viability decrease in SH-SY5Y neuroblastoma cells.
Assuntos
Peptídeos beta-Amiloides/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Flavonóis/isolamento & purificação , Flavonóis/farmacologia , Ginkgo biloba/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Fármacos Neuroprotetores/farmacologia , Folhas de Planta/química , Peptídeos beta-Amiloides/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Ésteres , Flavonóis/química , Glicosídeos/química , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Estrutura Molecular , Neuroblastoma/tratamento farmacológico , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Óxido Nítrico/biossíntese , Ressonância Magnética Nuclear Biomolecular , Fragmentos de Peptídeos/efeitos dos fármacos , Extratos Vegetais/farmacologiaRESUMO
Three unprecedented phloroglucinol-diterpene adducts, chlorabietols A-C (1-3), were isolated from the roots of the rare Chloranthaceae plant Chloranthus oldhamii. They represent a new class of compounds, featuring an abietane-type diterpenoid coupled with different alkenyl phloroglucinol units by forming a 2,3-dihydrofuran ring. Their structures were elucidated by detailed spectroscopic analysis, molecular modeling studies, and electronic circular dichroism calculations. Compounds 1-3 showed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 12.6, 5.3, and 4.9 µM, respectively.
Assuntos
Diterpenos/química , Furanos/química , Floroglucinol/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/farmacologia , Diterpenos/isolamento & purificação , Concentração Inibidora 50 , Estrutura Molecular , Floroglucinol/isolamento & purificação , Raízes de Plantas , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 1/químicaRESUMO
Fourteen new ent-abietane-type diterpenoids, sessilifols A-N (1-14), and three related new norditerpenoids (15-17) were isolated from Chloranthus sessilifolius. The absolute configurations were determined by single-crystal X-ray diffraction analysis, the modified Mosher's method, and/or the observed Cotton effects in their electronic circular dichroism spectra. Sessilifols A (1) and B (2) possess an uncommon five-membered C-ring rearranged by oxidative cleavage of the C-13/C-14 bond in abieta-7,13-diene followed by the formation of a new C-C bond between C-12 and C-14. Sessilifol C (3) is a rare 7,8-seco-9-spiro-fused ent-abietane, whereas sessilifol O (15) represents the first example of a naturally occurring 14-norabietane-type diterpenoid. Compounds 6 and 9 were found to have moderate antineuroinflammatory activities by inhibiting the nitric oxide production in lipopolysaccharide-stimulated murine BV-2 microglial cells, with IC50 values of 8.3 and 7.4 µM, respectively.
Assuntos
Abietanos/isolamento & purificação , Abietanos/farmacologia , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Magnoliopsida/química , Abietanos/química , Animais , Diterpenos/química , Medicamentos de Ervas Chinesas/química , Concentração Inibidora 50 , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Ressonância Magnética Nuclear BiomolecularRESUMO
Six new (leonurusoleanolides E-J, 1-6) and five known (7-11) nortriterpenoids were isolated and characterized from the dried fruits of Leonurus japonicus. They all contain a distinctive 19(18â17)-abeo-28-noroleanane-type spirocylclic skeleton with a trans or a cis acyl substituent at C-3 or C-23. Similar to the previously known leonurusoleanolides A/B (7/8) and C/D (9/10), compounds 1/2 and 3/4 were also found to exist as equilibrium mixtures of trans and cis isomers. The isolated pure compounds and mixtures were evaluated for their cytotoxicity against a small panel of human cancer cell lines (BGC-823 and KE-97 gastric carcinoma, Huh-7 hepatocarcinoma, Jurkat T cell lymphoblasts, and MCF-7 breast adenocarcinoma) using the CellTiter-Glo luminescent cell viability assay method. Among them, (2α,3ß,17R*,18ß)-3-O-(trans-caffeoyl)-19(18â17)-abeo-28-norolean-12-ene-2,18,23-triol (leonurusoleanolide J, 6) showed the most potent cytotoxic activity, with IC50 values less than 10 µM.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Leonurus/química , Compostos de Espiro/isolamento & purificação , Triterpenos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Frutas/química , Humanos , Concentração Inibidora 50 , Neoplasias Hepáticas , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Triterpenos/química , Triterpenos/farmacologiaRESUMO
Four novel naturally occurring diastereoisomers of dinor-eudesmenes, named chloranthones A-D (1-4, resp.), were isolated as minor components from the EtOH extract of the aerial parts of Chloranthus elatior. The unprecedented framework was established using extensive 2D-NMR techniques. Their absolute configurations were deduced from the observed Cotton effects in their circular dichroism (CD) spectra. A plausible biosynthetic pathway to the dinor-eudesmenes is proposed.
Assuntos
Produtos Biológicos/isolamento & purificação , Magnoliopsida/química , Sesquiterpenos/isolamento & purificação , Animais , Produtos Biológicos/química , Linhagem Celular , Humanos , Camundongos , Conformação Molecular , Sesquiterpenos/química , EstereoisomerismoRESUMO
Staphylococcus aureus can readily form biofilm which enhances the drug-resistance, resulting in life-threatening infections involving different organs. Biofilm formation occurs due to a series of developmental events including bacterial adhesion, aggregation, biofilm maturation, and dispersion, which are controlled by multiple regulatory systems. Rapidly increasing research and development outcomes on natural products targeting S. aureus biofilm formation and/or regulation led to an emergent application of active phytochemicals and combinations. This review aimed at providing an in-depth understanding of biofilm formation and regulation mechanisms for S. aureus, outlining the most important antibiofilm strategies and potential targets of natural products, and summarizing the latest progress in combating S. aureus biofilm with plant-derived natural products. These findings provided further evidence for novel antibiofilm drugs research and clinical therapies.
RESUMO
With the increasing prevalence of Staphylococcus aureus infections, rapid emergence of drug resistance and the slow healing of infected wounds, developing an efficient antibiotic-free multifunctional wound dressing for inhibiting S. aureus and simultaneously facilitating wound healing have become a huge challenge. Due to their excellent biocompatibility and biodegradability, some carbopol hydrogels based on plant extracts or purified compounds have already been applied in wound healing treatment. In China, Euphorbia humifusa Willd. (EuH) has been traditionally used as a medicine and food homologous medicine for the treatment of furuncles and carbuncles mainly caused by S. aureus infection. In an earlier study, EuH-originated flavonoids quercetin (QU) and luteolin (LU) could serve as a potential source for anti-S. aureus drug discovery when used in synergy. However, the in vivo effects of QU and LU on S. aureus-infected wound healing are still unknown. In this study, we found a series of Carbopol 940-based hydrogels loading QU and LU in combination could disinfect S. aureus and also could promote wound healing. In the full-thickness skin defect mouse model infected with S. aureus, the wound contraction ratio, bacterial burden, skin hyperplasia and inflammation score, as well as collagen deposition and blood vessels were then investigated. The results indicate that the optimized QL2 [QU (32 µg mL-1)-LU (8 µg mL-1)] hydrogel with biocompatibility significantly promoted S. aureus-infected wound healing through anti-infection, anti-inflammation, collagen deposition, and angiogenesis, revealing it as a promising alternative for infected wound repair.
RESUMO
An investigation on the secondary metabolites from a rice culture broth of the endophytic fungus Neurospora terricola HDF-Br-2 derived from the vulnerable conifer Pseudotsuga gaussenii led to the isolation and characterization of 34 structurally diverse polyketides (1-34). Seven of them are previously undescribed, including five unprecedented dihydropyran-containing (terricoxanthones A-E, 1-5, resp.) and one rare tetrahydrofuran-containing (terricoxanthone F, 6) dimeric xanthones. The structures were elucidated by spectroscopic methods and single-crystal X-ray diffraction analyses. Terricoxanthones each were obtained as a racemic mixture. Their plausible biosynthetic relationships were briefly proposed. Compounds 6, aspergillusone A (8), and alatinone (27) displayed considerable inhibition against Candida albicans with MIC values of 8-16 µg/mL. 4-Hydroxyvertixanthone (12) and 27 exhibited significant inhibitory activities against Staphylococcus aureus, with MIC values of 4-8 µg/mL. Furthermore, compounds 8 and 27 could disrupt biofilm of S. aureus and C. albicans at 128 µg/mL. The findings not only extend the skeletons of xanthone dimers and contribute to the diversity of metabolites of endophytes associated with the endangered Chinese conifer P. gaussenii, but could further reveal the important role of protecting plant species diversity in support of chemical diversity and potential sources of new therapeutics.
Assuntos
Neurospora , Pseudotsuga , Traqueófitas , Xantonas , Staphylococcus aureus , Fungos , Xantonas/química , Estrutura Molecular , Testes de Sensibilidade MicrobianaRESUMO
Ten new lycodine-type alkaloids, named casuarinines A-J (1-10), along with eight known analogues (11-18), were isolated from the whole plant of Lycopodiastrum casuarinoides . The new structures were established by spectroscopic methods and chemical transformations. Casuarinines A-D (1-4) and J (10) are common lycodine alkaloids possessing four connected six-membered rings, while tricyclic casuarinines E-H (5-8) are the piperidine ring cleavage products. In particular, casuarinine I (9) has an unprecedented five-membered tetrahydropyrrole ring instead of the piperidine ring. A plausible biosynthetic pathway to 9 is proposed. Among the compounds reported, casuarinine H (8) exhibited significant neuroprotective effect against hydrogen peroxide (H2O2)-induced neuronal cell damage in human neuroblastoma SH-SY5Y cells, while casuarinines C (3) and I (9) showed moderate inhibitory activity against acetylcholinesterase (AChE).
Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Lycopodiaceae/química , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Acetilcolinesterase/efeitos dos fármacos , Alcaloides/química , Inibidores da Colinesterase/química , Humanos , Peróxido de Hidrogênio/farmacologia , Estrutura Molecular , Neuroblastoma/tratamento farmacológico , Fármacos Neuroprotetores/química , Ressonância Magnética Nuclear Biomolecular , Piperidinas/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia humifusa Willd., known as Di-Jin-Cao in Chinese, has long been utilized as a traditional herb for the treatment of furuncles and carbuncles mainly caused by Staphylococcus aureus infection. Despite extensive chemical and pharmacological studies reported previously for E. humifusa, the antibacterial and antibiofilm activities against S. aureus as well as the related mechanism of action (MoA) remain largely obscure. AIM OF THE STUDY: To investigate the antibacterial and antibiofilm activities of the preferred fractions and compounds from E. humifusa against S. aureus and assess the associated MoA. MATERIALS AND METHODS: The bioactive fractions and compounds were obtained from the 75% ethanol extract of E. humifusa (75%-EEEH) with the assistance of the related antibacterial and antibiofilm screening. Their antibacterial activities were determined using the broth microdilution method, whilst the inhibition of biofilm formation and the disruption of preformed biofilm were assessed by crystal violet staining and confocal laser scanning microscopy (CLSM). To achieve more effective therapies, the combinatory effects of different components were also studied. The biofilm metabolic activities of isolated compounds were evaluated by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay. The scanning electron microscopy (SEM) and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to explore the antibiofilm mechanism. RESULTS: Fractions DJC06 and DJC07 collected from the ethyl acetate extract of the 75%-EEEH exhibited antibacterial activity (MIC = 256 µg/mL) against S. aureus and further separation of these two fractions led to the isolation and characterization of 22 compounds. Among the isolates, luteolin (LU), quercetin (QU), and kaempferol (KA) are the verified components associated with the antibacterial and antibiofilm activities by displaying individual or combinational MIC values of 8-128 µg/mL and 70.9-99.7% inhibition for biofilm formation. Importantly, QU and KA can work in synergy with LU to significantly enhance the efficacy via destroying cell integrity, increasing membrane permeability, and down-regulating the biofilm-related gene expression. CONCLUSIONS: The preferred fractions and compounds from E. humifusa exerted desired antibacterial and antibiofilm efficacy against S. aureus via a MoA involving cell morphology disruption and altered genes expression. The findings herein not only support its traditional use in the treatment of furuncles and carbuncles, but reveal E. humifusa is a potential source for producing promising antibiofilm alternatives against S. aureus and highlight the isolated components (LU, QU, KA) that can potentiate the efficacy when used in synergy.
Assuntos
Carbúnculo , Euphorbia , Furunculose , Infecções Estafilocócicas , Animais , Staphylococcus aureus , Antibacterianos/farmacologia , Infecções Estafilocócicas/microbiologia , Biofilmes , Testes de Sensibilidade MicrobianaRESUMO
Two new phloroglucinols, named eucalyptals D (1) and E (2), along with a related known compound (euglobal-In-3, 3) were isolated from the fruits of Eucalyptus globulus. Their structures were established on the basis of extensive spectroscopic studies, revealing that they share a common 3,5-diformyl-isopentyl phloroglucinol unit, but each is instead coupled to a different sesquiterpenoid skeleton (aromadendrene in 1, cadinene in 2, and a spirosesquiterpene in 3). Compound 1 possessed an unusual seven-membered D ring with an ether bridge between C-2 of the aromadendrene moiety and C-2' of the aromatic unit. The absolute configuration of the isolates was defined by the comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1-3 exhibited significant in vitro cytotoxicities against a few human cancer cell lines (Huh-7, Jurkat, BGC-823, and KE-97) using the CellTiter-Glo™ luminescent cell viability assay method.
RESUMO
In this review, we intensively focus on the advances in research of natural products (NPs) discovery carried out by domestic scholars in China from 2015 through 2017. In general, a total of 1811 publications (1479 in English and 332 in Chinese) were accumulated regarding newly isolated NPs from plants, microorganisms, and marine sources. As a result, 277 selected papers concerning naturally occurring compounds with extraordinary frameworks, origins, and promising activities were discussed in this review article, mainly organized according to their structural classes and novelties.
Assuntos
Produtos Biológicos/química , Descoberta de Drogas , Animais , Produtos Biológicos/história , Produtos Biológicos/farmacologia , China , Descoberta de Drogas/história , História do Século XXI , Humanos , Estrutura MolecularRESUMO
Two previously undescribed chimonanthine-type [sinodamines A and B] and five related known dimeric tryptamine-derived alkaloids were isolated and characterized from the leaves of the endangered ornamental plant Sinocalycanthus chinensis under the guidance of LC-MS detection and dereplication analyses, along with conventional isolation procedures. Their structures were established on the basis of spectroscopic methods and chemical transformations. Sinodamine A can be regarded as the naturally occurring N-oxide derivative of its pseudo-mesomer sinodamine B. An acid-catalyzed Meisenheimer rearrangement from sinodamine A to its oxazine-form with a final equilibrium of 1:2 was observed by monitoring their NMR spectra. (-)-Folicanthine showed significant cytotoxicity against human lung carcinoma A549 and colorectal carcinoma HT29â¯cells, with IC50 values of 7.76 and 6.16⯵M, respectively.
Assuntos
Alcaloides/farmacologia , Calycanthaceae/química , Alcaloides/química , Alcaloides/isolamento & purificação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Espécies em Perigo de Extinção , Células HT29 , Humanos , Espectrometria de Massas , Estrutura Molecular , Folhas de Planta/química , Relação Estrutura-AtividadeRESUMO
This study was intended to look for anti-HIV chemical constituents of aerial parts of Caragana rosea Turcz. Column chromatographic technique was used for the isolation and purification of constituents of Caragana rosea under the guide of anti-HIV assay. The structures were established on the basis of physical and chemical properties and spectroscopic data. Five compounds were obtained from the EtOAc fraction of aerial parts of Caragana rosea and identified as myricetin (1), mearnsetin (2), p-hydroxy cinnamic acid (3), cararosinol A (4) and cararosinol B (5). At the same time, one possible transformation route between cararosinol B and kobophenol A, another resveratrol tetramer isolated from this plant previously, was proposed. Compounds 4, 5 are new resveratrol tetramers, compounds 1 -3 were isolated from this plant for the first time. All compounds showed no activities in an in vitro assay against HIV-1.
Assuntos
Fármacos Anti-HIV/química , Benzofuranos/isolamento & purificação , Caragana/química , Componentes Aéreos da Planta/química , Plantas Medicinais/química , Estilbenos/isolamento & purificação , Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Benzofuranos/química , Benzofuranos/farmacologia , Ácidos Cumáricos/química , Ácidos Cumáricos/isolamento & purificação , Ácidos Cumáricos/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , HIV-1/efeitos dos fármacos , Estrutura Molecular , Propionatos , Estilbenos/química , Estilbenos/farmacologiaRESUMO
OBJECTIVE: To investigate whether mesenchymal stem cells (MSCs) transplantation after acute myocardial infarction (AMI) can improve heart function and decrease infarct size in rabbits and their correlation. METHODS: Twenty-four rabbits were randomly divided into AMI group and MSCs group, each n=12. Exogenous MSCs labeled with bromodeoxyuridine (BrdU) were injected into the border and central area of the ischemic myocardium. Heart function was assessed with echocardiography before transplantation of MSCs and in 6th week after the transplantation. Surviving MSCs in infarcted myocardium were identified by immunohistochemistry. Infarct size was measured histologically. Correlation of heart function and infarct size were analysed. RESULTS: Immunohistochemical stain revealed that BrdU-positive cells were seen in the infarcted myocardium in MSCs group but not in AMI group. Transplantation of MSCs was associated with a significant diminution of left ventricular end-diastolic dimension (LVEDD), and left ventricular end-systolic dimension (LVESD, both P<0.05), and left ventricular ejection fraction (LVEF) and fractional shortening (DeltaFS%)increased (both P<0.05) as compared with AMI group. Infarct size as measured histologically was significant smaller in MSCs group than AMI group (P<0.05). There were negative correlations between LVEF and infarct size in two groups (both P<0.01). CONCLUSION: Exogenous MSCs transplantation can improve heart function by decreasing infarct size and therefore it might be beneficial in the treatment of AMI.
Assuntos
Transplante de Células-Tronco Mesenquimais , Infarto do Miocárdio/fisiopatologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Masculino , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Coelhos , Distribuição Aleatória , Transplante HomólogoRESUMO
During a further and comprehensive phytochemical investigation on the shed trunk barks of the critically endangered plant Abies beshanzuensis, one new (1) and ten known (2-11) lignans with diverse structures were isolated. On the basis of spectroscopic methods, the new structure was established to be (7S,8R,8'R)-4'-methoxyl-α-conidendrin (1). Among the isolated lignans, (-)-matairesinol (5) and (-)-arctigenin (6) showed significant anti-neuroinflammatory activities by inhibiting the overproduction of nitric oxide in lipopolysaccharide-stimulated murine BV-2 microglial cells, with IC50 values of 11.5 and 19.0 µM, respectively.
Assuntos
Abies/química , Anti-Inflamatórios/isolamento & purificação , Lignanas/isolamento & purificação , Animais , Anti-Inflamatórios/farmacologia , Células Cultivadas , Furanos/farmacologia , Lignanas/química , Lignanas/farmacologia , Camundongos , Microglia/efeitos dos fármacos , Óxido Nítrico/biossíntese , Casca de Planta/químicaRESUMO
In search of anti-inflammatory lead compounds from traditional Chinese medicines, a bioassay-guided phytochemical study on Melastoma dodecandrum was carried out. As a result, 18 compounds have been isolated. Their chemical structures were determined on the basis of their physicochemical properties and spectral data. Among the isolates, three pentacyclic triterpenoids, ursolic acid (1), asiatic acid (3) and terminolic acid (6), together with one tannin casuarinin (17), were found to significantly decrease interleukin-8 (IL-8) production in human colon cancer cells. The results imply, at least in part, that the anti-inflammatory effect of M. dodecandrum could be due to inhibition of IL-8 production, demonstrated by these naturally occurring compounds described above.
Assuntos
Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Interleucina-8/efeitos dos fármacos , Melastomataceae/química , Taninos/isolamento & purificação , Taninos/farmacologia , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Anti-Inflamatórios/química , Medicamentos de Ervas Chinesas/química , Células HT29 , Humanos , Taninos Hidrolisáveis/isolamento & purificação , Interleucina-8/metabolismo , Estrutura Molecular , Triterpenos Pentacíclicos/isolamento & purificação , Folhas de Planta/química , Taninos/química , Triterpenos/química , Ácido UrsólicoRESUMO
One (formosumone A, 1) new and fifteen (2-16) known phenolic compounds were isolated from the leaves of Cratoxylum formosum ssp. pruniflorumm, a substitute for the popular bitter nail tea ("Kuding Tea") generally used in Southeast Asia. Their structures were determined by extensive spectroscopic analysis and by comparison with literature data. Compound 1 possesses a rare scaffold of a flavanone coupled with a phloroglucinol moiety, representing the first example of such a scaffold from the Clusiaceae family. Among the isolates, toxyloxanthone B (11) and vismione D (12) were found to show remarkable anti-neuroinflammatory effects by inhibiting nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine BV-2 microglial cells. Additionally, toxyloxanthone B (11) exhibited significant neuroprotective effect against ß-amyloid(25-35) (Aß(25-35))-induced cell viability decrease in SH-SY5Y neuroblastoma cells.
Assuntos
Anti-Inflamatórios/química , Clusiaceae/química , Flavonoides/química , Fármacos Neuroprotetores/química , Fenóis/química , Extratos Vegetais/química , Animais , Antraquinonas/química , Antraquinonas/isolamento & purificação , Antraquinonas/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Lipopolissacarídeos/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico/metabolismo , Fenóis/isolamento & purificação , Fenóis/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Folhas de Planta/química , Xantonas/química , Xantonas/isolamento & purificação , Xantonas/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The dried stems of Clematis armandii (Caulis clematidis armandii), named "Chuan-Mu-Tong" in Chinese Pharmacopoeia, have been traditionally used as an herbal remedy mainly for inflammation-associated diseases. The Aim of the study is to identify the potential anti-neuroinflammatory components from Clematis armandii. MATERIALS AND METHODS: The ethanol extract of "Chuan-Mu-Tong" was suspended in H2O and exhaustively extracted with CH2Cl2. The CH2Cl2 fraction was successively subjected to column chromatography (CC) over silica gel, Sephadex LH-20, and semi-preparative HPLC. The structures of the isolated compounds were identified by spectroscopic methods and by comparison with those reported in the literature. Their anti-neuroinflammatory activities were evaluated by inhibitory effects on pro-inflammatory mediators [e.g. nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α)] in lipopolysaccharide (LPS)-activated BV-2 cells. RESULTS: One new and sixteen known lignans were isolated and characterized. The absolute configuration of the new lignan, (7R,8S)-9-acetyl-dehydrodiconiferyl alcohol (1), was elucidated by a combination of 1D/2D NMR techniques and the Electronic Circular Dichroism (ECD) spectroscopy based on the empirical helicity rules. The anti-neuroinflammatory bioassay showed that compounds 1, (7R,8S)-dehydrodiconiferyl alcohol (2), erythro-guaiacylglycerol-ß-coniferyl ether (5), and threo-guaiacylglycerol-ß-coniferyl ether (6) displayed significant inhibitory effects on NO production. Among them, neolignans 1 and 2 exhibited more potent activities than the positive control (N(G)-monomethyl-L-arginine, L-NMMA), with an IC50 value of 9.3 and 3.9 µM, respectively. Moreover, both 1 and 2 were also found to concentration-dependently suppress the TNF-α release in LPS-stimulated BV-2 cells. CONCLUSION: The results revealed that lignans are the major components of "Chuan-Mu-Tong", and their anti-neuroinflammatory activities strongly support the traditional application of this herb medicine on inflammation. Moreover, the dihydrobenzo[b]furan neolignans 1 and 2 as well as Caulis clematidis armandii could be further exploited as new therapeutic agents to treat inflammation-mediated neurodegenerative and aging-associated diseases.