RESUMO
Six new C-20 and one new C-19 quassinoids, named perforalactones F-L (1-7), were isolated from twigs of Harrisonia perforata. Spectroscopic and X-ray crystallographic experiments were conducted to identify their structures. Through oxidative degradation of perforalactone B to perforaqussin A, the biogenetic process from C-25 quassinoid to C-20 via Baeyer-Villiger oxidation was proposed. Furthermore, the study evaluated the anti-Parkinson's disease potential of these C-20 quassinoids for the first time on 6-OHDA-induced PC12 cells and a Drosophila Parkinson's disease model of PINK1B9. Perforalactones G and I (2 and 4) showed a 10-15% increase in cell viability of the model cells at 50 µM, while compounds 2 and 4 (100 µM) significantly improved the climbing ability of PINK1B9 flies and increased the dopamine level in the brains and ATP content in the thoraces of the flies.
Assuntos
Doença de Parkinson , Quassinas , Simaroubaceae , Doença de Parkinson/tratamento farmacológico , Extratos Vegetais/farmacologia , Proteínas Quinases , Simaroubaceae/químicaRESUMO
Two new quassinoids (1 and 2) were isolated from the twigs of Harrisonia perforata (Blanco) Merr. Perforalactone E (2) possesses an uncommon hexacyclic 1α,12α:5α,13α-dicyclo-9ßH-picrasane skeleton. Its structure was determined based on spectroscopic data and X-ray crystallography. Compounds 1 and 2 could significantly induce lysosomal biogenesis through transcriptional activation of lysosomal genes.
Assuntos
SimaroubaceaeRESUMO
In this paper,metabolomics and network pharmacology were used to investigate the bioactive components of Harrisonia perforata and their possible mechanisms of action. Metabolites in the flowers,fruits,branches,leaves and stalks of H. perforata were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Meanwhile,multiple statistical analysis methods including principal component analysis( PCA) and orthogonal partial least squares discriminant analysis( OPLS-DA)were applied to screen and identify differential compounds. With metabolomics method,9 differential compounds were preliminarily identified from leaves and other non-traditional medicinal parts. Subsequently,these compounds were explored by using network pharmacology. With gastrointestinal absorption and drug-likeness as limiting conditions,they were imported into the Swiss ADME,from which 7 compounds with potential medicinal activity were obtained. Then,their targets were predicted by PharmMapper,with Human Protein Targets Only and Normalized Fit Score>0. 9 set as limiting conditions,and 60 standardized potential targets were identified with Uniprot. KEGG( Kyoto encyclopedia of genes and genomes) pathway data was obtained using metascape and the " potential active ingredients-target-pathway" network was constructed with Cytoscape 3. 7. 2. The enrichment analysis of KEGG demonstrated that the 60 targets were enriched in 78 signaling pathways( min overlap: 3,P value cutoff: 0. 01,min enrichment: 1. 5),many of which are related to anti-bacteria,anti-inflammation and anti-virus,such as IL-17 signaling pathway,RIG-I-like receptor signaling pathway and NOD-like receptor signaling pathway. Finally,depending on the clinical activity of H. perforata,the relevant signaling pathways were analyzed through experimental data and literature. Dehydroconiferyl alcohol was reported to have the anti-inflammatory effect and perforamone D to possess the antimycobacterial activity. The KEGG pathway enrichment analysis showed that dehydroconiferyl alcohol could act on the Alzheimer's disease( AD) signaling pathway by targeting CDK5 R1 and BACE1. ACh E inhibitor is the most promising drug to treat AD,while dehydroconiferyl alcohol has been proved to inhibit ACh E according to literature. The experimental results revealed that the extract of leaves of H. perforata can effectively inhibit the growth of Staphylococcus aureus. These are consistent with the enrichment analysis results of KEGG. This study explored the bioactive components and pharmacodynamics of the leaves of the H. perforata,laying a theoretical foundation for its in-depth development and rational application.
Assuntos
Medicamentos de Ervas Chinesas , Simaroubaceae , Secretases da Proteína Precursora do Amiloide , Ácido Aspártico Endopeptidases , Medicamentos de Ervas Chinesas/farmacologia , Humanos , MetabolômicaRESUMO
BACKGROUND: Lung cancer is a common leading cause of cancer-related death worldwide. Ailanthone, a natural compound isolated from Chinese herb Ailanthus altissima, has been reported to exert antiproliferative effects on various cancer cells. METHODS: The present study aimed to investigate the role of ailanthone in the lung cancer cells and the correlation between the ailanthone and microRNA (miR)-195. The cell viability, proliferation, and apoptosis were determined by cell counting kit-8 assay, bromodeoxyuridine incorporation method, annexin V-fluorescein isothiocyanate/propidium iodide assay, respectively. Apoptosis- and autophagy-related proteins, as well as regulatory factors in the signaling pathways, were analyzed by Western blot method. The expression of miR-195 was quantified by quantitative reverse transcription-polymerase chain reaction. RESULTS: The results confirmed that ailanthone was involved in the lung cancer cell progress by inhibiting cell viability and proliferation, but promoted cell apoptosis and autophagy. We also found that ailanthone upregulated the expression of miR-195. Further, the downregulated miR-195 inhibited the apoptosis and autophagy induced by ailanthone. Moreover, our studies revealed that miR-195 inhibitor promoted the phosphorylation of PI3K, AKT, JAK, and STAT3, which was inhibited by ailanthone. CONCLUSION: All these findings suggest that ailanthone plays key roles in lung cancer progress and is closely correlated with miR-195 expression.
Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , MicroRNAs/genética , Extratos Vegetais/farmacologia , Quassinas/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Humanos , Janus Quinases/genética , Janus Quinases/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Simaroubaceae/química , Células Tumorais CultivadasRESUMO
BACKGROUND AND AIM: Simaba ferruginea A.St.-Hil. Popularly known as "calunga," is a typical Brazilian cerrado plant whose rhizomes are popular for treating diarrhea. AIMS: The aim of this study was to evaluate the spasmolytic activity and the antidiarrheal effect of the ethanolic extract obtained from S. ferruginea (Sf-EtOH). METHODS: Ileal segments (1-2 cm) from male Wistar rats were mounted in isolated organ baths and connected to a force transducer, and then to an amplifier which was connected to a computer (AVS Projetos/São Paulo-SP). After stabilization for 60 min, under tension (1 gf), two submaximal contractions were induced with KCl 40 mM or carbachol 10-6 M on ileal segments. During the third tonic and sustained contraction, Sf-EtOH was added in cumulative concentrations to the organ bath. Incubations with L-NAME (10-4 M), ODQ (10-5 M), TEA+ (5 or 1 mM), glibenclamide (10-5 M), or apamine (100 nM) were prepared (n = 5), separately and used to verify the involvement of the nitric oxide synthase, guanylate cyclase, and potassium channels in the relaxing effect. The results were expressed as mean ± standard error of the mean and were statistically evaluated using one-way ANOVA followed by Bonferroni test, when necessary *p < 0.05. RESULTS: Sf-EtOH promotes relaxation on rat isolated ileum pre-contracted with CCh and KCl in a concentration-dependent manner. Sf-EtOH also inhibited ileum contractions against cumulative concentrations of carbachol (CCh), KCl, and CaCl2, shifting the curves to the right in a non-parallel manner with an Emax reduction. In the presence of potassium channel blockers, Sf-EtOH shifted the curves to the right with a reduction of Emax, suggesting the involvement of BKCa, KATP, and SKCa in its spasmolytic effect. In the presence of L-NAME or ODQ, the relaxation curves were shifted to the right, suggesting the involvement of this pathway in Sf-EtOH spasmolytic effect. CONCLUSIONS: Sf-EtOH acts in a concentration-dependent manner, involving the positive modulation of K+ channels and NO pathway.
Assuntos
Guanilato Ciclase/metabolismo , Íleo/metabolismo , Óxido Nítrico Sintase/metabolismo , Parassimpatolíticos/farmacologia , Canais de Potássio/metabolismo , Simaroubaceae , Animais , Relação Dose-Resposta a Droga , Íleo/efeitos dos fármacos , Masculino , Relaxantes Musculares Centrais/isolamento & purificação , Relaxantes Musculares Centrais/farmacologia , Técnicas de Cultura de Órgãos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Folhas de Planta , Ratos , Ratos WistarRESUMO
Simaba cedron Planch (Simaroubaceae) has frequently been reported as a traditional remedy against snake bites, malaria, gastrointestinal and other disorders. Starting in the 18th century, European physicians and researchers made several efforts to verify the reported virtues and to isolate active principles. Most important achievements are reviewed her. From modern investigations, an anti-malarial activity seems plausible due to the quassinoids contained. An effect against snake-bites seems questionable, research about the usefulness against gastrointestinal disorders, which is also reported, is missing. Other Simaroubaceae, however, are under current investigation now.
Assuntos
Medicina Tradicional/métodos , Preparações de Plantas/farmacologia , Simaroubaceae/química , Animais , Humanos , Preparações de Plantas/químicaRESUMO
The in vitro nematicidal effect of Chenopodium ambrosioides and Castela tortuosa n-hexane extracts (E-Cham and E-Cato, respectively) on Haemonchus contortus infective larvae (L3) and the anthelmintic effect of these extracts against the pre-adult stage of the parasite in gerbils were evaluated using both individual and combined extracts. The in vitro confrontation between larvae and extracts was performed in 24-well micro-titration plates. The results were considered 24 and 72 h post confrontation. The in vivo nematicidal effect was examined using gerbils as a study model. The extracts from the two assessed plants were obtained through maceration using n-hexane as an organic agent. Gerbils artificially infected with H. contortus L3 were treated intraperitoneally with the corresponding extract either individually or in combination. The results showed that the highest individual lethal in vitro effect (96.3%) was obtained with the E-Cham extract at 72 h post confrontation at 40 mg/ml, followed by E-Cato (78.9%) at 20 mg/ml after 72 h. The highest combined effect (98.7%) was obtained after 72 h at 40 mg/ml. The in vivo assay showed that the individual administration of the E-Cato and E-Cham extracts reduced the parasitic burden in gerbils by 27.1% and 45.8%, respectively. Furthermore, the anthelmintic efficacy increased to 57.3% when both extracts were administered in combination. The results of the present study show an important combined nematicidal effect of the two plant extracts assessed against L3 in gerbils.
Assuntos
Antinematódeos/uso terapêutico , Doenças das Aves/tratamento farmacológico , Chenopodium ambrosioides/química , Haemonchus/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Simaroubaceae/química , Animais , Doenças das Aves/parasitologia , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Gerbillinae/parasitologia , Hexanos , Injeções Intraperitoneais , Larva/efeitos dos fármacos , MasculinoRESUMO
Generic circumscriptions in the mostly pantropical family Simaroubaceae are somewhat controversial. Simaba is the largest genus, currently defined as exclusively neotropical, with around 25 species of trees and shrubs, but both its limits and infrageneric classification have been a matter of discussion and divergence. Traditionally, species of the genus have been treated in three sections: Simaba sect. Tenuiflorae, S. sect. Floribundae and S. sect. Grandiflorae, but a phylogenetic analysis suggested that the latter two may not be monophyletic. To test the monophyly of Simaba and its infrageneric classification, we used a molecular approach based on DNA sequence data from two nuclear ribosomal spacer regions (ITS and ETS) and three plastid regions (rps16 intron, and intergenic spacers psbA-trnH and trnL-trnF), including a comprehensive sampling of species from Simaba and closely related genera. We also performed ancestral character reconstructions to identify morphological characters that could serve as synapomorphies for major clades and to explore patterns of homoplasy in the morphological dataset. Our results show Simaba as traditionally circumscribed is not monophyletic, with taxa segregated into two strongly supported but distinct clades, one of which is more closely related to Simarouba. The three main clades that emerged in the phylogeny include a mostly Amazonian Simaba clade (which includes the type species of Simaba and the remaining species of S. sect. Tenuiflorae, here proposed to be recognized as Simaba sensu stricto), a mostly extra-Amazonian Simaba clade (a distinct lineage that will be recognized as Homalolepis, a genus currently treated in synonymy and equivalent to Simaba sections Grandiflorae and Floribundae), and the Simarouba clade (including all of its current species). These three clades are characterized by a combination of morphological characters, described in detail herein, some of which are novel features for Simaba not previously reported in the literature. Mapping character-states on the phylogenetic tree provides tests for evolutionary hypotheses. For example, our reconstruction of habit and geographic distribution suggests that the diversification of several shrubby species within the extra-Amazonian lineage in the South American cerrados probably occurred from ancestors inhabiting tropical forests, involving transitions in morphological and ecological traits.
Assuntos
Filogenia , Simaroubaceae/classificação , Simaroubaceae/genética , Sequência de Bases , Teorema de Bayes , Núcleo Celular/genética , Sequência Consenso , DNA de Plantas/genética , Geografia , Íntrons/genética , Análise de Sequência de DNA , Simaroubaceae/anatomia & histologia , Simaroubaceae/ultraestrutura , Especificidade da EspécieRESUMO
BACKGROUND: Malaria is an infectious disease caused by parasites of the genus Plasmodium, of which Plasmodium vivax and Plasmodium falciparum are the major species that cause the disease in humans. As there are relatively few alternatives for malaria treatment, it is necessary to search for new chemotherapeutic options. Colombia possesses a great diversity of plants, which are potential sources of new compounds of medical interest. Thus, in this study the antiplasmodial effect of extracts from two species of plants from the families Simaroubaceae and Picramniaceae (Picramnia latifolia and Picrolemma huberi) was evaluated in vitro and in vivo. These plants were chosen because they contain secondary metabolites with interesting medicinal effects. RESULTS: The ethanolic extracts of both species were highly active with IC50: 1.2 ± 0.19 µg/mL for P. latifolia and IC50: 0.05 ± 0.005 µg/mL for P. huberi. The P. latifolia extract had a stage specific effect on trophozoites and inhibited parasite growth in vivo by 52.1 ± 3.4%, evaluated at 1000 mg/kg in Balb/c mice infected with Plasmodium berghei. On the other hand, evaluated at 150 mg/kg body weight in the same murine model, the ethanolic extract from P. huberi had an antiplasmodial effect in all the asexual intraerythrocytic stages of P. falciparum FCR3 and inhibited the parasitic growth in 93 ± 32.9%. CONCLUSIONS: This is the first report of anti-malarial activity for these two species of plants. Thus, P. latifolia and P. huberi are potential candidates for the development of new drugs for treating malaria.
Assuntos
Antimaláricos/farmacologia , Extratos Vegetais/farmacologia , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Simaroubaceae/química , Animais , Camundongos/parasitologia , Camundongos Endogâmicos BALB C/parasitologia , Especificidade da EspécieRESUMO
A new alkaloid, Canthin-6-one, Huberine (1), together with three known compounds including 1-Hydroxy-canthin-6-one (2), Canthin-6-one (3) and stigma sterol (4), were isolated from the stem bark of Picrolemma huberi. The isolation was achieved by chromatographic techniques and the purification was performed on a C18 column using acetonitrile/water (90:10, v/v) with 0.1% formic acid as the mobile phase. The structural elucidation was performed via spectroscopic methods, notably 1D- and 2D-NMR, UV, IR, MS and HRMS. The antiplasmodial activity of the compounds was studied.
Assuntos
Alcaloides/química , Carbolinas/química , Alcaloides Indólicos/química , Casca de Planta/química , Simaroubaceae/químicaRESUMO
Quassinoids often exhibit antioxidant and antiproliferative activity. Emerging evidence suggests that these natural metabolites also display chemopreventive actions. In this study, we investigated the potential for the quassinoid glaucarubulone glucoside (Gg), isolated from the endemic Jamaican plant Castela macrophylla (Simaroubaceae), to display potent cytotoxicity and inhibit human cytochrome P450s (CYPs), particularly CYP1A enzymes, known to convert polyaromatic hydrocarbons into carcinogenic metabolites. Gg reduced the viability of MCF-7 breast adenocarcinoma cells (IC50 = 121 nm) to a greater extent than standard of care anticancer agents 5-fluorouracil, tamoxifen (IC50 >10 µm) and the tamoxifen metabolite 4-hydroxytamoxifen (IC50 = 2.6 µm), yet was not cytotoxic to non-tumorigenic MCF-10A breast epithelial cells. Additionally, Gg induced MCF-7 breast cancer cell death. Gg blocked increases in reactive oxygen species in MCF-10A cells mediated by the polyaromatic hydrocarbon benzo[a]pyrene (B[a]P) metabolite B[a]P 1,6-quinone, yet downregulated the expression of genes that promote antioxidant activity in MCF-7 cells. This implies that Gg exhibits antioxidant and cytoprotective actions in non-tumorigenic breast epithelial cells and pro-oxidant, cytotoxic actions in breast cancer cells. Furthermore, Gg inhibited the activities of human CYP1A according to non-competitive kinetics and attenuated the ability of B[a]P to induce CYP1A gene expression in MCF-7 cells. These data indicate that Gg selectively suppresses MCF-7 breast cancer cell growth without impacting non-tumorigenic breast epithelial cells and blocks B[a]P-mediated CYP1A induction. Taken together, our data provide a rationale for further investigations of Gg and similar plant isolates as potential agents to treat and prevent breast cancer. Copyright © 2017 John Wiley & Sons, Ltd.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Citotoxinas/uso terapêutico , Glaucarubina/análogos & derivados , Extratos Vegetais/uso terapêutico , Simaroubaceae/química , Antioxidantes/uso terapêutico , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Feminino , Expressão Gênica/efeitos dos fármacos , Glaucarubina/uso terapêutico , Humanos , Jamaica , Células MCF-7/efeitos dos fármacos , Quassinas/uso terapêuticoRESUMO
Isobrucein B (1) is a quassinoid isolated from the Amazonian medicinal plant Picrolemma sprucei. Herein we investigate the anti-inflammatory and antihyperalgesic effects of this quassinoid. Isobrucein B (1) (0.5-5 mg/kg) inhibited carrageenan-induced inflammatory hyperalgesia in mice in a dose-dependent manner. Reduced hyperalgesia was associated with reduction in both neutrophil migration and pronociceptive cytokine production. Pretreatment with 1 inhibited in vitro production/release of cytokines TNF, IL-1ß, and KC/CXCL1 by lipopolysaccharide-stimulated macrophages. To investigate its molecular mechanism, RAW 264.7 macrophages with a luciferase reporter gene controlled by the NF-κB promoter were used (RAW 264.7-Luc). Quassinoid 1 reduced the luminescence emission by RAW 264.7-Luc stimulated by different compounds. Unexpectedly, NF-κB translocation to macrophage nuclei was not inhibited by 1 when evaluated by Western blotting and immunofluorescence. Furthermore, quassinoid 1 did not change the levels of TNF mRNA transcription in stimulated macrophages, suggesting post-transcriptional modulation. In addition, constitutive expression of luciferase in RAW 264.7 cells transiently transfected with a plasmid containing a universal promoter was inhibited by 1. Thus, isobrucein B (1) displays anti-inflammatory and antihyperalgesic activities by nonselective post-transcriptional modulation, resulting in decreased production/release of pro-inflammatory cytokines and neutrophil migration.
Assuntos
Citocinas/metabolismo , Hiperalgesia/tratamento farmacológico , Plantas Medicinais/química , Quassinas/farmacologia , Simaroubaceae/química , Animais , Anti-Inflamatórios/farmacologia , Brasil , Carragenina/efeitos adversos , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Proteínas I-kappa B/efeitos dos fármacos , Inflamação/induzido quimicamente , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Estrutura Molecular , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Peroxidase/metabolismo , Quassinas/química , Fator de Necrose Tumoral alfa/efeitos dos fármacosRESUMO
This study was performed to investigate the chemical constituents in the twigs and leaves of Harrisonia perforate. Six compounds were isolated from the 95% EtOH extract of the twigs and leaves of Harrisonia perforate by silica gel, ODS, Sephadex LH-20 column chromatographies and preparative HPLC. On the basis of chemical properties and spectra data, these compounds were identified as harriperfin E (1), kihadanin A (2), kihadanin B (3), 6α-acetoxyobacunol acetate (4), gardaubryone C (5), and ß-sitosterol methyl ether (6), respectively. Compound 1 is a new chromone, and compounds 2-6 are isolated from this plant for the first time.
Assuntos
Compostos Fitoquímicos/química , Folhas de Planta/química , Simaroubaceae/química , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Compostos Fitoquímicos/isolamento & purificaçãoRESUMO
Perforalactoneâ A (1), a new 20S quassinoid with a unique cagelike 2,4-dioxaadamantane ring system and a migrated side chain, was isolated from the plant Harrisonia perforata together with two biosynthetically related new quassinoids. The structures of these natural products were elucidated by NMR spectroscopy, X-ray diffraction analysis, computational modeling, and the CD excitation chirality method. The compounds exhibited notable biological properties, including insecticidal activity against Aphis medicaginis Koch and antagonist activity at the nicotinic acetylcholine receptor of Drosophila melanogaster. The structural features of these compounds may be related to their promising biological characteristics. Their biosynthesis and an alternative origin of quassinoid-type natural products are also discussed.
Assuntos
Produtos Biológicos/farmacologia , Besouros/efeitos dos fármacos , Inseticidas/farmacologia , Quassinas/farmacologia , Receptores Nicotínicos/metabolismo , Simaroubaceae/química , Animais , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Relação Dose-Resposta a Droga , Drosophila melanogaster/química , Drosophila melanogaster/metabolismo , Inseticidas/química , Inseticidas/metabolismo , Conformação Molecular , Quassinas/biossíntese , Quassinas/química , Simaroubaceae/metabolismo , Relação Estrutura-AtividadeRESUMO
Aromatase (CYP 19A1) is a key steroidogenic enzyme that catalyzes the conversion of androgen to estrogen. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for aromatase inhibitor screening was developed and validated. The substrate androstenedione was incubated with human CYP 19A1 supersomes in the presence of NADPH for 30 min, and estrone formation was determined by LC-MS/MS analysis. Cortisone was used as internal standard. The incubation mixture was extracted using a liquid-liquid extraction method with ethyl acetate. Chromatographic separation was achieved using a C18 column (3.0 × 50 mm, 2.7 µm) with a mobile phase consisting of 0.1% formic acid/acetonitrile adopting gradient elution at a flow rate of 0.4 mL/min. The mass spectrometer was operated in positive electrospray ionization mode. The precursor-product ion pairs used for multiple reaction monitoring were m/z 287â97 (androstenedione), m/z 271 â 159 (estrone), and m/z 361 â 163 (IS, cortisone). The developed method met the required criteria for the validation of bioanalytical methods. The validated method was successfully applied to evaluate aromatase inhibitory activity of plants extracts of Simaroubaceae.
Assuntos
Inibidores da Aromatase/análise , Aromatase/química , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão , Cortisona/química , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Estrona/química , Humanos , Extração Líquido-Líquido , Extratos Vegetais , Reprodutibilidade dos Testes , SimaroubaceaeRESUMO
Benjalokawichien (BLW) or Ya-Ha-Rak (HR) is a traditional remedy in the Nationaldrug list of herbal medicinal products AD 2012 of Thailand. For traditional use, BLW is used as antipyretic agent. It also has anti-allergic effect, particularly treating allergic rash. The ethanolic extract of BLW exhibited anti-allergic activity via inhibitory effect against a release ofbeta-hexosaminidase in RBL-2H3 cell line. Pectolinarigenin has been identified as the active compound ofBLW extract. In this study, a reversed-phase high performance liquid chromatography (RP-HPLC) method was developed in order to control quality ofpreparation in three aspects such as chemical fingerprint, quantification and stability of the ethanolic extract. The RP-HPLC was performed with a gradient mobile phase composed of 0.1% ortho phosphoric acid and acetronitrile, and peaks were detected at 331 nm. Based on validation results, this analytical method is precise, accurate and stable for quantitative determination ofpectolinarigenin. The amount ofpectolinarigenin in Benjalokawichien extract determined by this method was 18.50 mg/g ofextract. Therefore, this method could be consideredfor quality control ofBLWextract.
Assuntos
Antialérgicos/química , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Preparações de Plantas/química , Capparis/química , Cromonas/química , Clerodendrum/química , Ficus/química , Humanos , Menispermaceae/química , Raízes de Plantas/química , Controle de Qualidade , Simaroubaceae/química , TailândiaRESUMO
Two new rearranged limonoids, harperforatin (1) and harperfolide (2), and a new chromone, harperamone (3), were isolated from fruits and roots of Harrisonia perforata, together with eight known compounds. Their structures were elucidated on the basis of spectroscopic data. Harperfolide (2) exhibited potent anti-inflammatory activity by suppressing nitric oxide (NO) production from activated macrophages with IC50 value of 6.51 µM. Furthermore, its effect is mediated by reduction of iNOS protein expression, attributable to the inhibitory action of LPS-induced NO production.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Cromonas/farmacologia , Limoninas/farmacologia , Simaroubaceae/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Cromonas/química , Cromonas/isolamento & purificação , Relação Dose-Resposta a Droga , Limoninas/química , Limoninas/isolamento & purificação , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Modelos Moleculares , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/biossíntese , Relação Estrutura-AtividadeRESUMO
The canthines represent a fairly large subclass of ß-carboline alkaloids, with the first members described 75 years ago. Over the last 60 years, many members of the parent compound, canthin-6-one (1), have been isolated from various plant sources, principally the Rutaceae and Simaroubaceae families, and recently from fungi. Structures isolated from these sources have been the subject of total synthesis, which continues to the present day. This review gives a broad overview of synthetic approaches to canthines over a 30-year period from 1982 to 2012 and summarizes recent reports on the synthesis of less well known ring-truncated congeners. These include C-ring-truncated ("ABD", 2) and A-ring-truncated ("BCD", 3) ring systems, which are providing new scaffolds for potentially useful therapeutic applications.
Assuntos
Alcaloides , Carbolinas , Rutaceae/química , Simaroubaceae/química , Alcaloides/síntese química , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Carbolinas/síntese química , Carbolinas/química , Carbolinas/isolamento & purificação , Carbolinas/farmacologia , Alcaloides Indólicos/síntese química , Alcaloides Indólicos/química , Estrutura Molecular , EstereoisomerismoRESUMO
OBJECTIVE: To study the chemical constituents in the fruit of Harrisonia perforata. METHODS: The chemical constituents were isolated and purified by means of chromatographic techniques and their structures were elucidated by analysis of spectroscopic data and physicochemical properties. RESULTS: Eight compounds were isolated and identified as caryolane-1,9beta-diol (1), gallic acid (2), 4-O-ethylgallic acid (3), syringic acid ethyl ester (4), protocatechuic acid (5), stigmasterol (6), beta-daucoster (7), beta-sitosterol (8). CONCLUSION: Compounds 1, 3 - 5 and 7 are isolated from this plant for the first time. Compounds 1, 3 and 4 are isolated from this genus for the first time.
Assuntos
Frutas/química , Ácido Gálico/análogos & derivados , Hidroxibenzoatos/química , Simaroubaceae/química , beta Caroteno/química , Cromatografia em Camada Fina , Ácido Gálico/química , Ácido Gálico/isolamento & purificação , Hidroxibenzoatos/isolamento & purificação , Estrutura Molecular , beta Caroteno/isolamento & purificaçãoRESUMO
BACKGROUND: Cancer remains a global health concern and constitutes an important barrier to increasing life expectancy. Malignant cells rapidly develop drug resistance leading to many clinical therapeutic failures. The importance of medicinal plants as an alternative to classical drug discovery to fight cancer is well known. Brucea antidysenterica is an African medicinal plant traditionally used to treat cancer, dysentery, malaria, diarrhea, stomach aches, helminthic infections, fever, and asthma. The present work was designed to identify the cytotoxic constituents of Brucea antidysenterica on a broad range of cancer cell lines and to demonstrate the mode of induction of apoptosis of the most active samples. METHODS: Seven phytochemicals were isolated from the leaves (BAL) and stem (BAS) extract of Brucea antidysenterica by column chromatography and structurally elucidated using spectroscopic techniques. The antiproliferative effects of the crude extracts and compounds against 9 human cancer cell lines were evaluated by the resazurin reduction assay (RRA). The activity in cell lines was assessed by the Caspase-Glo assay. The cell cycle distribution, apoptosis via propidium iodide (PI) staining, mitochondrial membrane potential (MMP) through 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining, and the reactive oxygen species (ROS) via 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFH-DA) staining, were investigated by flow cytometry. RESULTS: Phytochemical studies of the botanicals (BAL and BAS) led to the isolation of seven compounds. BAL and its constituents 3, (3-(3-Methyl-1-oxo-2-butenyl))1H indole (1) and hydnocarpin (2), as well as the reference compound, doxorubicin, had antiproliferative activity against 9 cancer cell lines. The IC50 values varied from 17.42 µg/mL (against CCRF-CEM leukemia cells) to 38.70 µg/mL (against HCT116 p53-/- colon adenocarcinoma cells) for BAL, from 19.11 µM (against CCRF-CEM cells) to 47.50 µM (against MDA-MB-231-BCRP adenocarcinoma cells) for compound 1, and from 4.07 µM (against MDA-MB-231-pcDNA cells) to 11.44 µM (against HCT116 p53+/+ cells) for compound 2. Interestingly, hypersensitivity of resistant cancer cells to compound 2 was also observed. BAL and hydnocarpin induced apoptosis in CCRF-CEM cells mediated by caspase activation, the alteration of MMP, and increased ROS levels. CONCLUSION: BAL and its constituents, mostly compound 2, are potential antiproliferative products from Brucea antidysenterica. Other studies will be necessary in the perspective of the discovery of new antiproliferative agents to fight against resistance to anticancer drugs.