RESUMO
Much confusion exists about the chemical composition of widely sold Cannabis sativa products that utilize the cannabidiol (CBD) acronym and related terms such as "CBD oil", "CBD plus hemp oil", "full spectrum CBD", "broad spectrum CBD", and "cannabinoids". Their rational chemical and subsequent biological assessment requires both knowledge of the chemical complexity and the characterization of significant individual constituents. Applicable to hemp preparations in general, this study demonstrates how the combination of liquid-liquid-based separation techniques, NMR analysis, and quantum mechanical-based NMR interpretation facilitates the process of natural product composition analysis by allowing specific structural characterization and absolute quantitation of cannabinoids present in such products with a large dynamic range. Countercurrent separation of a commercial "CBD oil" yielded high-purity CBD plus a more polar cannabinoid fraction containing cannabigerol and cannabidivarin, as well as a less polar cannabinoid fraction containing cannabichromene, trans-Δ9-tetrahydrocannabinol, cis-Δ9-tetrahydrocannabinol, and cannabinol. Representatives of six cannabinoid classes were identified within a narrow range of polarity, which underscores the relevance of residual complexity in biomedical research on cannabinoids. Characterization of the individual components and their quantitation in mixed fractions were undertaken by TLC, HPLC, 1H (q)NMR spectroscopy, 1H iterative full spin analysis (HiFSA), 13C NMR, and 2D NMR. The developed workflow and resulting analytical data enhance the reproducible evaluation of "CBD et al." products, which inevitably represent complex mixtures of varying molecular populations, structures, abundances, and polarity features.
Assuntos
Canabidiol , Canabinoides , Cannabis , Alucinógenos , Analgésicos , Canabinoides/química , Cannabis/química , Dronabinol , Extratos Vegetais/químicaRESUMO
Weed, an abundant biomass, is considered unsuitable as a raw material for methane production. There are few reports on the anaerobic digestion of weeds without the addition of other organic wastes. To solve this problem, a methane-producing microbial community with weed as a sole feedstock was established. This study mainly focused on the degree of contribution between water-soluble and -insoluble fractions of the weed to methane production; thus, methane production from both fractions was tested separately. Methane production after 80-day batch cultures with whole weed, water-soluble and water-insoluble fractions was 184.5, 96.8 and 26.5 NmL g-1 dry matter (DM), respectively. The results of 16S rRNA gene amplicon sequence analysis revealed that Proteiniphilum saccharofermentans and several Methanobacterium species commonly dominated all cultures, whereas the population dynamics of minor species differed in every culture. Moreover, the remixed culture of microbial communities adapted to water-soluble and -insoluble fractions recovered methane production (252.4 NmL g-1 DM). Based on these results, it can be strongly inferred that colocalizing the minor species in water-soluble and -insoluble fractions is important for effective methane production.
Assuntos
Cynodon/microbiologia , Metano/metabolismo , Microbiota , Plantas Daninhas/microbiologia , Biomassa , Reatores Biológicos/microbiologia , Cynodon/química , Ácidos Graxos Voláteis/metabolismo , Concentração de Íons de Hidrogênio , Plantas Daninhas/química , Água/químicaRESUMO
Mogroside V is one of the characteristic and effective components of luohanguo extract, a food additive used as a sweetener in Japan as per Japan's Standards and Specifications for Food Additives (JSFA; 9th ed.). JSFA stipulates that the quantitative determination for mogroside V content in luohanguo extract applies HPLC using analytical standard mogroside V. However, no mogroside V reagents with proven purities are commercially available. Therefore the current JSFA determination method is not particularly suited for daily quality control operations involving luohanguo extract. In this study, we applied an alternative quantitative method using a single reference with relative molar sensitivity (RMS). It was possible to calculate the accurate RMS by an offline combination of 1H-quantitative NMR spectroscopy (1H-qNMR) and an HPLC/variable-wavelength detector (VWD). Using the RMS of mogroside V to a commercial certified reference material grade caffeine, the mogroside V contents in luohanguo extracts could be determined using HPLC/VWD without analytical standard mogroside V. There was no significant difference between the mogroside V contents in luohanguo extracts determined using the method employing single-reference caffeine with the RMS and using the JSFA method. The absolute calibration curve for the latter was prepared using an analytical standard mogroside V whose purity was determined by 1H-qNMR. These results demonstrate that our proposed method using a single reference with RMS is suitable for quantitative determination of mogroside V in luohanguo extract and can be used as an alternative method to the current assay method in JSFA.
Assuntos
Cafeína/análise , Cucurbitaceae/química , Aditivos Alimentares/análise , Extratos Vegetais/análise , Triterpenos/análise , Cafeína/normas , Cromatografia Líquida de Alta Pressão/normas , Aditivos Alimentares/normas , Japão , Espectroscopia de Ressonância Magnética/normas , Extratos Vegetais/normas , Controle de Qualidade , Triterpenos/normasRESUMO
"Licorice oil extract" (LOE) (antioxidant agent) is described in the notice of Japanese food additive regulations as a material obtained from the roots and/or rhizomes of Glycyrrhiza uralensis, G. inflata or G. glabra. In this study, we aimed to identify the original Glycyrrhiza species of eight food additive products using LC/MS. Glabridin, a characteristic compound in G. glabra, was specifically detected in seven products, and licochalcone A, a characteristic compound in G. inflata, was detected in one product. In addition, Principal Component Analysis (PCA) (a kind of multivariate analysis) using the data of LC/MS or (1)H-NMR analysis was performed. The data of thirty-one samples, including LOE products used as food additives, ethanol extracts of various Glycyrrhiza species and commercially available Glycyrrhiza species-derived products were assessed. Based on the PCA results, the majority of LOE products was confirmed to be derived from G. glabra. This study suggests that PCA using (1)H-NMR analysis data is a simple and useful method to identify the plant species of origin of natural food additive products.
Assuntos
Aditivos Alimentares/química , Glycyrrhiza/química , Glycyrrhiza/classificação , Extratos Vegetais/química , Óleos de Plantas/química , Raízes de Plantas/química , Chalconas/análise , Cromatografia Líquida , Etanol , Isoflavonas/análise , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas , Fenóis/análise , PrótonsRESUMO
In our screening program for natural products that increase death-receptor 5 expression, seven new cycloartane triterpenes, euphonerins A-G (1-7), and 3-O-acetyl-8-O-tigloylingol (8), a new ingol diterpene, were isolated from the MeOH extract of Euphorbia neriifolia leaves, together with 3,12-di-O-acetyl-8-O-tigloylingol (9), (24R)-cycloartane-3ß,24,25-triol (10), and three known flavonols (11-13). The structures of 1-8 were elucidated by spectroscopic analysis. Among these compounds, 1-11 showed death-receptor 5 expression enhancing activity.
Assuntos
Diterpenos/química , Diterpenos/farmacologia , Euphorbia/química , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/efeitos dos fármacos , Triterpenos/química , Triterpenos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Diterpenos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Extratos Vegetais/farmacologia , Folhas de Planta/química , Triterpenos/isolamento & purificação , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Bioassay guided separation of Sida acuta whole plants led to the isolation of an alkaloid, cryptolepine (1), along with two kaempferol glycosides (2-3). Compound 1 showed strong activity in overcoming TRAIL-resistance in human gastric adenocarcinoma (AGS) cells at 1.25, 2.5 and 5 µm. Combined treatment of 1 and TRAIL sensitized AGS cells to TRAIL-induced apoptosis at the aforementioned concentrations.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Alcaloides Indólicos/farmacologia , Malvaceae/química , Quinolinas/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Adenocarcinoma/patologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Ativação Enzimática/efeitos dos fármacos , Glicosídeos/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/isolamento & purificação , Quinolinas/química , Quinolinas/isolamento & purificação , Neoplasias Gástricas/patologiaRESUMO
In search of bioactive natural products for overcoming TRAIL resistance from natural resources, we previously reported a number of active compounds. Bioassay-guided fractionation of mangrove, Amoora cucullata, collected from Sundarbans Mangrove Forest, Bangladesh, led to the isolation of four new compounds (1-4), along with seven known compounds (5-11). Of the isolates, compounds 1, 5, 8, and 9 showed TRAIL resistance-overcoming activity, among which 8 showed the most potent activity and enhanced TRAIL-induced apoptosis in TRAIL-resistant human gastric adenocarcinoma (AGS) cells through the activation of caspase-3/7, enhancing the expression of DR4 and DR5 mRNA in AGS cells. Cell death caused by the combined treatment of 8 and TRAIL was inhibited by human recombinant DR5/Fc and DR4/Fc chimera proteins, indicating that 8 sensitizes TRAIL-resistant AGS cells to TRAIL through the induction of DR4 and DR5.
Assuntos
Meliaceae/química , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/antagonistas & inibidores , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Modelos Moleculares , Conformação Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Receptores do Fator de Necrose Tumoral/genéticaRESUMO
A screening study using a luciferase assay to identify natural products that enhance death receptor 5 (DR5) expression was carried out, and bioassay-guided fractionation of two organisms, the pericarp of Garcinia mangostana (mangosteen) and actinomycete CKK609 strain, led to the isolation of eight xanthone derivatives (1-8) and teleocidin A-2 (9). Among them, compounds 1, 2, and 5, isolated from G. mangostana, and 9, from the actinomycete, showed potent DR5 promoter activity. Furthermore, we revealed that combined treatment with gartanin (5) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) showed a potentiation effect in sensitizing TRAIL-resistant human gastric adenocarcinoma (AGS) cells. Thus, the present results suggested that 5 has the ability to overcome TRAIL resistance via the up-regulation of DR5 and may be an effective sensitizer of TRAIL-resistant cells.
Assuntos
Apoptose/efeitos dos fármacos , Garcinia/química , Toxinas de Lyngbya/isolamento & purificação , Toxinas de Lyngbya/farmacologia , Plantas Medicinais/química , Receptores de Morte Celular/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Xantonas/isolamento & purificação , Xantonas/farmacologia , Humanos , Toxinas de Lyngbya/química , Estrutura Molecular , Receptores de Morte Celular/genética , Ligante Indutor de Apoptose Relacionado a TNF/efeitos dos fármacos , Tailândia , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/genética , Regulação para Cima , Xantonas/químicaRESUMO
The TRAIL/death-receptor signaling pathway has been considered a promising target for selective cancer therapy, although some malignant tumors exhibit TRAIL resistance. We previously found that isoflavonoid enhanced TRAIL-induced apoptosis in TRAIL-resistant cells, which is achieved through up-regulation of death receptor 5 (DR5). In our screening program targeting DR5 promoter enhancement activity, activity-guided fractionations of the extract of Catimbium speciosum led to the isolation of six compounds. Of the isolates, cardamomin (6), the most potent compound, enhanced the expressions of DR5 and DR4 and decreased the Bcl-xL level in TRAIL-resistant DLD1 cells. The combination of 6 and TRAIL synergistically enhanced TRAIL-induced apoptosis against TRAIL-resistant cells upon the activation of caspase-8, 9, and 3. In addition, enhancement of apoptosis by 6 was inhibited by human recombinant DR5/Fc and DR4/Fc chimera proteins, TRAIL-neutralizing fusion proteins, indicating that 6 sensitize TRAIL-resistant cells to TRAIL through the induction of DR5 and DR4. Also, up-regulation of DR5 by 6 paralleled that of CCAAT/enhancer-binding protein-homologous protein (CHOP).
Assuntos
Alpinia/química , Apoptose/efeitos dos fármacos , Chalconas/farmacologia , Regiões Promotoras Genéticas/efeitos dos fármacos , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Linhagem Celular Tumoral , Chalconas/química , Chalconas/isolamento & purificação , Humanos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Rizoma/química , Regulação para Cima/efeitos dos fármacosRESUMO
A screening study for TRAIL resistance-overcoming activity was carried out, and activity-guided fractionations of Thevetia peruviana and Sapindus emarginatus led to the isolation of four cardenolide glycosides (1-4) and four triterpenoid saponins (5-8), respectively. In particular, cardenolide glycosides (1 and 2) from T. peruviana were shown to have a significant reversal effect on TRAIL resistance in human gastric adenocarcinoma cells, and real-time PCR showed that thevefolin (2) enhanced mRNA expression of death receptor 4 (DR4) and DR5. In addition, 1H and 13C NMR characterizations are shown for thevefolin (2) for the first time.
Assuntos
Cardenolídeos/isolamento & purificação , Cardenolídeos/farmacologia , Plantas Medicinais/química , Sapindus/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/efeitos dos fármacos , Thevetia/química , Sequência de Bases , Cardenolídeos/química , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Saponinas/química , Neoplasias Gástricas/metabolismo , Tailândia , Células Tumorais CultivadasRESUMO
A new monoterpene glycoside (1) isolated from the aerial part of Sibirae angustata RCHD. (Rosaceae) was found to be 1-O-beta-D-glucopyranosyl-geraniol-5,10-olide and named as sibiskoside. Acute toxicity study revealed that oral administration of 1 (2.5 g/kg body weight) to mice resulted in no death and no evidence of abnormalities in internal organs. Its oral administration to the mice reared with high-fat diet resulted in weight-loss, which was also reflected in serum triglyceride and sugar level, and the weight of abdominal fat. Sibiskoside could be considered to be an active ingredient of Liucha for exerting weight-loss effect in a drink of S. angustata.
Assuntos
Fármacos Antiobesidade/química , Glicosídeos/química , Monoterpenos/química , Rosaceae/química , Monoterpenos Acíclicos , Administração Oral , Animais , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/toxicidade , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Glicosídeos/toxicidade , Camundongos , Monoterpenos/isolamento & purificação , Monoterpenos/farmacologia , Monoterpenos/toxicidade , Extratos Vegetais/químicaRESUMO
Aberrant Wnt/beta-catenin signaling has recently been implicated in tumorigenesis. On the basis of our screening program targeting inhibition of TCF/beta-catenin transcriptional activity, a plant extract of Eleutherine palmifolia was selected as a hit sample. Activity-guided fractionations led to the isolation of 15 naphthalene derivatives (1-15), including 4 new glucosides, eleutherinosides B-E (1-4), and 10 of the 15 compounds showed strong activities with high viability among 293T cells. Our data showed that 2 and 9 inhibited the transcription of TCF/beta-catenin in SW480 colon cancer cells in a dose-dependent manner. These two compounds also showed selective cytotoxicity against three colorectal cancer cell lines. In addition, treatment with 9 led to a significant decrease in the level of nuclear beta-catenin protein, suggesting this reduction to have resulted in the inhibitory effect of 9 on the transcription of TCF/beta-catenin.
Assuntos
Glicosídeos/química , Iridaceae/química , Naftalenos/química , Proteínas Wnt/antagonistas & inibidores , beta Catenina/antagonistas & inibidores , Linhagem Celular Tumoral , Glicosídeos/isolamento & purificação , Glicosídeos/toxicidade , Humanos , Naftalenos/isolamento & purificação , Naftalenos/toxicidade , Extratos Vegetais/química , Raízes de Plantas/química , Transdução de Sinais , Relação Estrutura-Atividade , Proteínas Wnt/metabolismo , beta Catenina/metabolismoRESUMO
An androstanoid, hoyasterone (1), a sesquiterpene, 15-bulnesolic acid (2), and a phenolic compound, 1-(4-hydroxy-3-methoxyphenyl)-1-methoxypropan-2-ol (3), together with a known triterpene, dihydrocanaric acid, were isolated from Hoya parasitica. Structures were elucidated by 1 D and 2 D NMR and mass spectroscopic analysis. Among the isolated compounds, only dihydrocanaric acid exhibited growth inhibitory activity against both HeLa and SW480 cells.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Apocynaceae/química , Proliferação de Células/efeitos dos fármacos , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Células HeLa , Humanos , Estrutura MolecularRESUMO
Two new acylated triterpenoid saponins were isolated from the branches of Schima noronhae by bioassay-guided purification. Their chemical structures were established on the basis of spectroscopic analysis and chemical means as 3-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-galactopyranosyl-(1-->3)-[beta-D-glucopyranosyl-(1-->2)]-beta-D-glucuronopyranosyl 22-O-angeloyl-A1-barrigenol (1) and 3-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-galactopyranosyl-(1-->3)-[beta-D-glucopyranosyl-(1-->2)]-beta-D-glucuronopyranosyl 22-O-angeloylerythrodiol (2). Compounds 1 and 2 showed cell growth inhibitory activity against both HeLa and DLD1 cells at a concentration of less than 10 microM.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Plantas Medicinais/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Theaceae/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Saponinas/química , Tailândia , Triterpenos/químicaRESUMO
Investigation of collagenase inhibitory natural components afforded two quinic acid esters (1 and 2) and quercetin (3) from the leaves of Pluchea indica (Compositae). Of these, compounds 1 and 2 exhibited collagenase inhibitory activity (IC(50)) at a concentration of less than 10 microm, and 1 showed matrix metalloproteinase (MMP)-2 and -9 inhibitory activity (IC(50)) at 2.5 and 6.4 microm, respectively.
Assuntos
Asteraceae/química , Inibidores de Metaloproteinases de Matriz , Extratos Vegetais/farmacologia , Ácido Quínico/farmacologia , Relação Dose-Resposta a Droga , Ésteres , Estrutura Molecular , Extratos Vegetais/química , Ácido Quínico/químicaRESUMO
Nine sesquiterpenes and eight flavonoids were isolated from Zingiber spectabile for the first time. Structures were determined by spectroscopic methods. The major compound zerumbone (1) was found to be the most active (IC(50) 13 microg mL(-1)) in cell growth inhibitory assay against colon carcinoma SW480 cells.
Assuntos
Flavonoides/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Zingiberaceae/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Flavonoides/química , Flavonoides/farmacologia , Células HeLa , Humanos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
A screening study on neuraminidase inhibitory constituents was carried out, and activity-guided fractionations of three plants, Gouania obtusifolia, Zizyphus cambodiana, and Mangifera odorata, led to the isolation of eleven compounds (1-11). Mangiferin was identified as a significant neuraminidase inhibitor.
Assuntos
Inibidores Enzimáticos/farmacologia , Neuraminidase/antagonistas & inibidores , Fitoterapia , Plantas Medicinais , Xantonas/farmacologia , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/uso terapêutico , Humanos , Concentração Inibidora 50 , Mangifera , Neuraminidase/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta , Rhamnaceae , Xantonas/administração & dosagem , Xantonas/uso terapêutico , ZiziphusRESUMO
Secoiridoid glucosides, 2''-epifraxamoside and demethyl-2''-epifraxamoside, and the secoiridoid, jasminanhydride were isolated from Jasminum grandiflorum together with four previously known phenolics and a triterpene. Structures were elucidated by detailed spectroscopic analysis. Stereochemistry of the compounds was determined by differential NOE experiment.
Assuntos
Iridoides/química , Jasminum/química , Proliferação de Células/efeitos dos fármacos , Células HeLa , Humanos , Iridoides/isolamento & purificação , Iridoides/farmacologia , Ressonância Magnética Nuclear Biomolecular , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Extratos Vegetais/química , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologiaRESUMO
Methanol extract from cultured Scutellaria baicalensis cells inhibited the proliferation of human monocytic leukemia cell line THP-1 and human osteogenic sarcoma cell line HOS. The inhibitory effects of baicalin, baicalein and wogonin, the three major flavonoids contained in the extract, were studied. It should be noted that wogonin did not show the inhibitory effect on human fetal lung normal diploid cell line TIG-1, as compared to the inhibition observed in cancer cells. Physiological analyses in THP-1 cells showed that wogonin induced cell cycle arrest at G(2)/M phase and apoptosis. This is the first report discovering a cancer-specific apoptosis-inducing activity of wogonin.
Assuntos
Apoptose/efeitos dos fármacos , Flavanonas/farmacologia , Inibidores do Crescimento/farmacologia , Scutellaria baicalensis/química , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Diploide , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Fase G2/efeitos dos fármacos , Humanos , Neoplasias/genética , Neoplasias/patologia , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
According to the traditional medicinal usage of Sonneratia caseolaris, we tested the extract of S. caseolaris for antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect on thin-layer chromatography. Following activity-oriented separation, two flavonoids, luteolin (1) and luteolin 7-O-ß-glucoside (2), were isolated. Both of the compounds were found to possess antioxidant activity.