RESUMO
Antrocaryon klaineanum is traditionally used for the treatment of back pain, malaria, female sterility, chlamydiae infections, liver diseases, wounds, and hemorrhoid. This work aimed at investigating the bioactive compounds with antileishmanial and antiplasmodial activities from A. klaineanum. An unreported glucocerebroside antroklaicerebroside (1) together with five known compounds (2-6) were isolated from the root barks of Antrocaryon klaineanum using chromatographic techniques. The NMR, MS, and IR spectroscopic data in association with previous literature were used for the characterization of all the isolated compounds. Compounds 1-4 are reported for the first time from A. klaineanum. The methanol crude extract (AK-MeOH), the n-hexane fraction (AK-Hex), the dichloromethane fraction (AK-DCM), the ethyl acetate fraction (AK-EtOAc), and compounds 1-6 were all evaluated for their antiparasitic effects against Plasmodium falciparum strains susceptible to chloroquine (3D7), resistant to chloroquine (Dd2), and promastigotes of Leishmania donovani (MHOM/SD/62/1S). The AK-Hex, AK-EtOAc, AK-MeOH, and compound 2 were strongly active against Dd2 strain with IC50 ranging from 2.78 ± 0.06 to 9.30 ± 0.29 µg/mL. Particularly, AK-MeOH was the most active-more than the reference drugs used-with an IC50 of 2.78 ± 0.06 µg/mL. The AK-EtOAc as well as all the tested compounds showed strong antileishmanial activities with IC50 ranging from 4.80 ± 0.13 to 9.14 ± 0.96 µg/mL.
Assuntos
Anacardiaceae , Antimaláricos , Antiprotozoários , Antimaláricos/farmacologia , Antimaláricos/química , Anacardiaceae/química , Extratos Vegetais/química , Antiprotozoários/farmacologia , Cloroquina , Plasmodium falciparumRESUMO
Phytochemical investigation of the aerial roots of Ficus sur, a Cameroonian medicinal plant, resulted in a previously undescribed cerebroside, suroside (1), in addition to its aglycon congener suramide (2). Moreover, six known natural products including alpinumisoflavone (3), wighteone metabolite (4), oleanolic acid (5), ß-sitosterol (6), ß-sitosterol-3-O-ß-D-glucopyranoside (7), and epi-ѱ-taraxastanolone (8) were identified. The structures of the previously undescribed compounds were determined by analysis of 1D and 2D-NMR (One and two dimensional nuclear magnetic resonance), mass spectrometry, chemical conversion, and by comparison of these data with those from the literature. Wighteone metabolite (4) exhibited a weak cytotoxic activity against the human HepG2 hepatocellular carcinoma cells with an IC50 value of 51.9 µM.
Assuntos
Ficus , Plantas Medicinais , Humanos , Ficus/química , Plantas Medicinais/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Cerebrosídeos , Extratos Vegetais/farmacologiaRESUMO
We previously reported that the ethanol extract from polished rice suppresses inflammation and the formation of aberrant crypt foci in the mouse colon and particularly focused on the plant sphingolipid glucosylceramide (GlcCer). Here, we investigated the effects of rice lipid fractions and GlcCer on differentiated Caco-2 cells treated with lipopolysaccharide (LPS), in particular, we evaluated the mechanism of action of GlcCer using related substances and metabolic enzyme inhibitors. Rice-derived polar lipids suppressed the LPS-induced reduction in the number of cells. The polar lipids with higher GlcCer content exerted a better effect than the other fractions. GlcCer-related substances reversed the LPS-induced reduction in the number of cells, and GlcCer-metabolic inhibitors, including a sphingosine kinase inhibitor, suppressed the beneficial effects of GlcCer-related substances. These results suggest that GlcCer is a rice component with intestinal protection. Secondly, GlcCer is metabolized during inflammation and protects intestinal cells by maintaining the sphingolipid levels in cells and producing sphingoid base-1-phosphate.
Assuntos
Glucosilceramidas , Oryza , Animais , Células CACO-2 , Humanos , Camundongos , Extratos Vegetais/farmacologia , EsfingolipídeosRESUMO
A new steroidal ester bearing n-nonadecanoyl moiety (1) and a mixture of isomeric cerebrosides (2) along with two known compounds were isolated from the methanol extract of the stem-bark of Anacardium occidentale. The structure of the new steroidal ester was determined as 3-n-nonadecanoyl-ß-sitosterol on the basis of modern spectroscopic techniques (IR, ESI-MS, HR-ESIMS, 1D and 2D NMR) and chemical degradation studies. The structures of the known compounds were identified as gallic acid and tanacetene by comparison of the spectroscopic data with those of reported data. The mixture of cerebrosides was confirmed based on the analysis of 1D and 2D NMR. These compounds were evaluated for cytotoxicity against human cancer cell lines A549, SCOV3 and rat normal cell line NRK49f.
Assuntos
Anacardium/química , Casca de Planta/química , Caules de Planta/química , Sitosteroides/isolamento & purificação , Animais , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular Tumoral , Humanos , Concentração Inibidora 50 , Extratos Vegetais/química , Espectroscopia de Prótons por Ressonância Magnética , Ratos , Sitosteroides/farmacologiaRESUMO
Termitomyces is a genus of edible mushrooms commonly consumed in Africa and Asia among the mushrooms collected from the wild. Termitomyces mushrooms grow as symbionts in the termite nests, where they produce various enzymes to help termites digest lignocellulosic substrates. Many species of Termitomyces are used by different ethnic groups with ethnomedicinal knowledge. Bioactive components that Termitomyces mushrooms contain have potential uses as antioxidants, immunomodulators, antitumors, and antimicrobials. Termitomyces also has a potential for treating neurodegenerative disorders. Here, we review the bioactive compounds from Termitomyces species that have been isolated and assayed in vitro and/or in vivo for their medicinal properties.
Assuntos
Medicina Tradicional do Leste Asiático , Termitomyces/química , Animais , Antibacterianos/química , Antibacterianos/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Ásia , Fatores Imunológicos/química , Fatores Imunológicos/metabolismo , Isópteros/microbiologiaRESUMO
Clavicorona pyxidata is a wild edible and medicinal mushroom that is rich in bioactive natural products and has thus been extensively used as traditional medicine in China. The present study has determined that the organic crude extract prepared from a fermented culture of C. pyxidata imparted auto-inhibitory effects on mycelial growth and then induced the formation of fruiting bodies. By monitoring bioactivity, one compound was isolated via successive chromatography over silica gel, Sephadex LH-20, and Cl8-reversed phase silica gel and was identified as a known sphingosine-type cerebroside by nuclear magnetic resonance (NMR) and physicochemical data, namely, (4E, 8E)-N-D-2'-hydroxypalmitoyl-1-O-ß-D-glucopyranosyl-9-methyl-4,8-sphingadienine. The application of this cerebroside at a concentration of 200 µg/disc paper resulted in the inhibition of aerial hyphal growth of C. pyxidata. The findings of the present study indicated that this C. pyxidata cerebroside is a fruiting body-inducing substance (FIS).
Assuntos
Agaricales/química , Agaricales/efeitos dos fármacos , Cerebrosídeos/química , Carpóforos/efeitos dos fármacos , Esfingosina/química , Cerebrosídeos/isolamento & purificação , Cerebrosídeos/farmacologia , China , Fermentação , Frutas/química , Espectroscopia de Ressonância MagnéticaRESUMO
Sphingolipids from marine sources have attracted more attention recently because of their distinctive structures and expected functions. In this study, the content and components of cerebroside from sea cucumber Stichopus japonicus were analyzed. The absorption of cerebroside from S. japonicus was investigated with an in vivo lipid absorption assay. The result revealed that S. japonicus is a rich source of cerebroside that contained considerable amounts of odd carbon chain sphingoid bases. The cumulative recoveries of d17:1- and d19:2-containing cerebrosides were 0.31 ± 0.16 and 0.32 ± 0.10%, respectively, for 24 h after administration. To the best of the authors' knowledge, this is the first work that shows sphingolipids from a marine source could be absorbed in vivo and incorporated into ceramides. In addition, dietary supplementation with sea cucumber cerebroside to hairless mouse improved the skin barrier function and increased short-chain fatty acids in cecal contents, which have shown beneficial effects on the host.
Assuntos
Ceco/metabolismo , Cerebrosídeos/metabolismo , Ácidos Graxos Voláteis/metabolismo , Pele/metabolismo , Stichopus/química , Animais , Ceco/química , Cerebrosídeos/química , Suplementos Nutricionais/análise , Ácidos Graxos Voláteis/química , Feminino , Masculino , Camundongos , Camundongos Pelados , Ratos , Ratos Sprague-Dawley , Pele/químicaRESUMO
Silica gel, Sephadex LH-20, and reverse phase (C-18) column chromatography were used for the research of chemical constituents occurred in Arisaema flavum(Forsk.) Schott. The structures were elucidated by comparison physico-chemical properties and NMR spectroscopic data with those of known compounds. Seventeen cerebrosides were identified as 1-O-ß-D-glucopyranosyl-(2S, 3R, 4E, 8E)-2-[(2'(R)-acetoxyoctadecanoyl)amido]-4, 8-octadecadiene-1, 3-diol (1), 2'-O-acetylsoyacerebroside I (2), 1-O-(ß-D-glucopyranosyl)-(2S, 3R, 4E, 13Z)-2-[(2'R)-2-hydroxytetradecanoylamino]-1, 3-dihydroxy-4, 13-docosadiene (3), (2S, 3R, 4E, 8E)1-(ß-D-glucopyranosyl)-3-hydroxy-2-[(R)-2'-hydroxyhexadecanoyl]amino-9-methyl-4, 8-heptadecadiene (4), (2S, 3R, 4E, 8E)1-(ß-D-glucopyranosyl)-3-hydroxy-2-[(R)-2'-hydroxyhexadecanoyl]amino-9-methyl-4, 8-octadecadiene (5), (2S, 3R, 4E, 8E)1-(ß-D-glucopyranosyl)-3-hydroxy-2-[(R)-2'-hydroxypalmitoyl]amino-9-methyl-4, 8-octadecadiene (6), (2S, 3R, 4E, 8E)1-(ß-D-glucopyranosyl)-3-hydroxy-2-[(R)-2'-hydroxyoctadecanoyl]amino-9-methyl-4, 8-octadecadiene (7), 1-O-(ß-D-glucopyranosyl)-(2S, 3R, 4E, 8E)-2-[(R)-2'-hydroxytetradecanoylamino]-4, 8-octadecadiene-1, 3-diol (8), 1-O-(ß-D-glucopyranosyl)-(2S, 3R, 4E, 8E)-2-[(R)-2'-hydroxypentadecanoylamino]-4, 8-octadecadiene-1, 3-diol (9), 1-O-(ß-D-glucopyranosyl)-(2S, 3R, 4E, 8E)-2-[(R)-2'-hydroxyhexadecanoylamino]-4, 8-octadecadiene-1, 3-diol (10), 1-O-(ß-D-glucopyranosyl)-(2S, 3R, 4E, 8Z)-2-[(R)-2'-hydroxyhexadecanoylamino]-4, 8-octadecadiene-1, 3-diol (11), 1-O-(ß-D-glucopyranosyl)-(2S, 3R, 4E, 8E)-2-[(R)-2'-hydroxyoctadecanoylamino]-1, 3-hydroxy-4, 8-octadecadiene (12), 1-O-(ß-D-glucopyranosyl)-(2S, 3R, 4E)-2-[(R)-2'-hydroxytetracosanoylamino]-1, 3-hydroxy-4-hexadecane (13), 1-O-(ß-D-glucopyranosyl)-(2S, 3R, 4R, 8Z)-2N-[(2'R)-2'-hydroxytetracosanoyl]-8-(Z)-octadecene-1, 3, 4-triol (14), 1-O-(ß-D-glucopyranosyl)-(2S, 3S, 4E, 8E)-2N-[(2'R)-2'-hydroxyhexadecanoyl]-4-(E), 8-(Z)-octadecadiene-1, 3-diol (15), typhoniside A (16), and 1-O-ß-D-glucopyranosyl-(2S, 3R, 8E)-2-[(2'R)-2-hydroxypalmitoylamino]-8-octadecene-1, 3-diol (17). Compounds 1 and 2 were isolated from the plant for the first time, while the remained compounds were isolated from the genus Arisaema for the first time.
Assuntos
Arisaema/química , Cerebrosídeos/análise , Dextranos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Compostos Fitoquímicos/análiseRESUMO
A new cerebroside, cerebroside E (1) was isolated from the fruiting bodies of Hericium erinaceus (Hericiaceae). The structure of 1 was elucidated by a combination of extensive spectroscopic analyses, including extensive 2D NMR, HR-MS, and chemical reactions. Compound 1 was evaluated for its applicability to medicinal use in several human diseases using cell-based assays. As a result, compound 1 attenuated cisplatin-induced nephrotoxicity in LLC-PK1 cells and exhibited a significant inhibitory effect on angiogenesis in HUVECs. These results collectively reflect the beneficial effects of compound 1 in cancer treatment.
Assuntos
Basidiomycota/química , Cerebrosídeos/química , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Animais , Basidiomycota/metabolismo , Cerebrosídeos/isolamento & purificação , Cerebrosídeos/farmacologia , Carpóforos/química , Carpóforos/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Células LLC-PK1 , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Conformação Molecular , Neovascularização Fisiológica/efeitos dos fármacos , SuínosRESUMO
Our previous study reported that cerebrosides from traditional Chinese medicine Baifuzi directly interact with the STREX domain of BKCa channels, which in turn results in the therapeutic effect of Baifuzi on ischemic stroke. However, it is not known how cerebrosides in the plasma membrane could interact with the STREX domain that is in the cytoplasmic side. Using patch-clamp technique, effects of different cerebrosides on the BKCa channel were studied by measuring single channel currents in CHO cells expressing wild type or mutated BKCa channels. Palmitoylation of the STREX domain was removed either by site-directed mutagenesis or pharmacological inhibition. Removal of palmitoylation sites at C646 and C647 by mutating the residues to Ala abolished the ability of cerebrosides to activate the BKCa channel. In contrast, the mutation neither changed the single channel conductance nor voltage sensitivity of the channel. Both palmitoylation inhibitors tunicamycin and palmitic acid analog 2-bromopalmitate attenuated the activation of the BKCa channel by cerebrosides. Furthermore, confocal images on STREX-EGFP fragments demonstrated that STREX fragments no longer associated with the plasma membrane when the palmitoylation was removed or blocked. These findings suggest that palmitoylation of the STREX domain is necessary for cerebrosides to activate the BKCa channel and provide insight into the mechanism of how Baifuzi could exert therapeutic effect on ischemic stroke.
Assuntos
Proteínas Aviárias/metabolismo , Membrana Celular/metabolismo , Cerebrosídeos/farmacologia , Ativação do Canal Iônico/efeitos dos fármacos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Lipoilação/fisiologia , Animais , Proteínas Aviárias/química , Proteínas Aviárias/genética , Células CHO , Membrana Celular/química , Membrana Celular/genética , Cerebrosídeos/química , Galinhas , Cricetinae , Cricetulus , Humanos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/química , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Lipoilação/efeitos dos fármacos , Medicina Tradicional Chinesa/métodos , Mutagênese Sítio-Dirigida , Mutação de Sentido Incorreto , Técnicas de Patch-Clamp , Estrutura Terciária de Proteína , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/metabolismoRESUMO
From the hexane and ethyl acetate extracts of the leaves of Sesbania aculeata, three novel chemical compounds were isolated and fully characterized as compound 1, (ceramide type); compound 2, (cerebroside type) and compound 3 as a triterpene acid 3-O-α-L-rhamnopyranoside along with nine known compounds (Tricontanol, Lauric acid, Palmitic acid, Heptadecanoyl-1-tridecanoic acid, ß-sitosterol, stigmasterol, poriferasterol glucoside, ononitol and pinitol). The anti-inflammatory potential of all three compounds were evaluated using in vitro target based anti-inflammatory activity in LPS-stimulated macrophages. TNF-α is one of the mediators of various chronic inflammatory disorders and treatment of hexane leaf extract (HL), Ethyl acetate leaf extract (EAL) and compounds 1, 2 and 3 at a dose of 10 µg/mL showed significant (P<0.001) inhibition of TNF-α, a pro-inflammatory cytokine. IL-6 was significantly (P<0.05) inhibited by compound 1 and HL at a dose of 10 µg/mL as compared with vehicle treatment. In-vitro cell cytotoxicity study using MTT assay revealed that these compounds were non toxic to the normal cells.
Assuntos
Anti-Inflamatórios/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Sesbania/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Feminino , Interleucina-6/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Our previous study reported that a mixture of cerebrosides from traditional Chinese medicine Baifuzi could activate BKCa channel. It is curious to know the effect of each single cerebroside on the channel. Here we isolated 5 pure cerebrosides from the mixture and determined their chemical structures. The most potent one increased the single channel open probability 6 folds with EC50 value of 1.0 µM. The structure-activity relationship revealed that acyl chain length of cerebrosides has potent effect, while configuration of double bond at C8-C9 on their long chain base has weak effect on the channel activity. Thus, this research provides a guide for design and synthesis of a lead cerebroside with more potent effect on the BKCa channel.