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1.
Chemistry ; 30(27): e202400272, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38445549

RESUMO

Springtails use unique compounds for their outermost epicuticular wax layer, often of terpenoid origin. We report here the structure and synthesis of socialane, the major cuticular constituent of the Collembola Hypogastrura socialis. Socialane is also the first regular nonaprenyl terpene with a cyclic head group. The saturated side chain has seven stereogenic centers, making the determination of the configuration difficult. We describe here the identification of socialane and a synthetic approach using the building blocks farnesol and phytol, enantioselective hydrogenation, and α-alkylation of sulfones for the synthesis of various stereoisomers. NMR experiments showed the presence of an anti-configuration of the methyl groups closest to the benzene ring and that the other methyl groups of the polyprenyl side-chain are not uniformly configured. Furthermore, socialane is structurally different from [6+2]-terpene viaticene of the closely related H. viatica, showing species specificity of the epicuticular lipids of this genus and hinting at a possible role of surface lipids in the communication of these gregarious arthropods.


Assuntos
Artrópodes , Terpenos , Animais , Estereoisomerismo , Terpenos/química , Artrópodes/química , Lipídeos/química , Farneseno Álcool/química , Farneseno Álcool/análogos & derivados , Fitol/química , Espectroscopia de Ressonância Magnética , Hidrogenação
2.
Anticancer Agents Med Chem ; 24(10): 773-788, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38415491

RESUMO

BACKGROUND: Non-Small Cell Lung Cancer (NSCLC) is a malignancy with a significant prevalence and aggressive nature, posing a considerable challenge in terms of therapeutic interventions. Autophagy and apoptosis, two intricate cellular processes, are integral to NSCLC pathophysiology, each affecting the other through shared signaling pathways. Phytol (Phy) and α-bisabolol (Bis) have shown promise as potential anticancer agents individually, but their combined effects in NSCLC have not been extensively investigated. OBJECTIVE: The present study was to examine the synergistic impact of Phy and Bis on NSCLC cells, particularly in the context of autophagy modulation, and to elucidate the resulting differential protein expression using LCMS/ MS analysis. METHODS: The A549 cell lines were subjected to the patented effective concentration of Phy and Bis, and subsequently, the viability of the cells was evaluated utilizing the MTT assay. The present study utilized real-time PCR analysis to assess the expression levels of crucial apoptotic genes, specifically Bcl-2, Bax, and Caspase-9, as well as autophagy-related genes, including Beclin-1, SQSTM1, Ulk1, and LC3B. The confirmation of autophagy marker expression (Beclin-1, LC3B) and the autophagy-regulating protein SQSTM1 was achieved through the utilization of Western blot analysis. Differentially expressed proteins were found using LC-MS/MS analysis. RESULTS: The combination of Phy and Bis demonstrated significant inhibition of NSCLC cell growth, indicating their synergistic effect. Real-time PCR analysis revealed a shift towards apoptosis, with downregulation of Bcl-2 and upregulation of Bax and Caspase-9, suggesting a shift towards apoptosis. Genes associated with autophagy regulation, including Beclin-1, SQSTM1 (p62), Ulk1, and LC3B, showed significant upregulation, indicating potential induction of autophagy. Western blot analysis confirmed increased expression of autophagy markers, such as Beclin-1 and LC3B, while the autophagy-regulating protein SQSTM1 exhibited a significant decrease. LC-MS/MS analysis revealed differential expression of 861 proteins, reflecting the modulation of cellular processes. Protein-protein interaction network analysis highlighted key proteins involved in apoptotic and autophagic pathways, including STOML2, YWHAB, POX2, B2M, CDA, CAPN2, TXN, ECHS1, PEBP1, PFN1, CDC42, TUBB1, HSPB1, PXN, FGF2, and BAG3, emphasizing their crucial roles. Additionally, PANTHER pathway analysis uncovered enriched pathways associated with the differentially expressed proteins, revealing their involvement in a diverse range of biological processes, encompassing cell signaling, metabolism, and cellular stress responses. CONCLUSION: The combined treatment of Phy and Bis exerts a synergistic inhibitory effect on NSCLC cell growth, mediated through the interplay of apoptosis and autophagy. The differential protein expression observed, along with the identified proteins and enriched pathways, provides valuable insights into the underlying molecular mechanisms. These findings offer a foundation for further exploration of the therapeutic potential of Phy and Bis in the management of NSCLC.


Assuntos
Apoptose , Autofagia , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Fitol , Espectrometria de Massas em Tandem , Humanos , Autofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fitol/farmacologia , Fitol/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células A549 , Proteoma/efeitos dos fármacos , Proteoma/metabolismo , Cromatografia Líquida , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Relação Estrutura-Atividade , Estrutura Molecular , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Sinergismo Farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Células Tumorais Cultivadas , Sesquiterpenos/farmacologia , Sesquiterpenos/química
3.
Naunyn Schmiedebergs Arch Pharmacol ; 397(7): 5131-5144, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38240783

RESUMO

This study explored the potential of poly-(lactic-co-glycolic) acid (PLGA) nanoparticles to enhance the effectiveness of anticancer treatments through combination therapy with phytol and α-bisabolol. The encapsulation efficiency of the nanoparticles was investigated, highlighting the role of ionic interactions between the drugs and the polymer. Characterization of PLGA-Phy+Bis nanoparticles was carried out using DLS with zeta potential and HR-TEM for size determination. Spectrophotometric measurements evaluated the encapsulation efficiency, loading efficiency, and in vitro drug release. FTIR analysis assessed the chemical interactions between PLGA and the drug actives, ensuring nanoparticle stability. GC-MS was employed to analyze the chemical composition of drug-loaded PLGA nanocarriers. Cytotoxicity was evaluated via the MTT assay, while Annexin V-FITC/PI staining and western blot analysis confirmed apoptotic cell death. Additionally, toxicity tests were performed on L-132 cells and in vivo zebrafish embryos. The study demonstrates high encapsulation efficiency of PLGA-Phy+Bis nanoparticles, which exhibit monodispersity and sizes of 189.3±5nm (DLS) and 268±54 nm (HR-TEM). Spectrophotometric analysis confirmed efficient drug encapsulation and release control. FTIR analysis revealed nanoparticle structural stability without chemical interactions. MTT assay results demonstrated the promising anticancer potential of all the three nanoparticle types (PLGA-Phy, PLGA-Bis, and PLGA-Phy+Bis) against lung cancer cells. Apoptosis was confirmed through Annexin V-FITC/PI staining and western blot analysis, which also revealed changes in Bax and Bcl-2 protein expression. Furthermore, the nanoparticles exhibited non-toxicity in L-132 cells and zebrafish embryo toxicity tests. PLGA-Phy+Bis nanoparticles exhibited efficient encapsulation, controlled release, and low toxicity. Apoptosis induction in A549 cells and non-toxicity in healthy cells highlight their clinical potential.


Assuntos
Apoptose , Sinergismo Farmacológico , Neoplasias Pulmonares , Sesquiterpenos Monocíclicos , Nanopartículas , Fitol , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Peixe-Zebra , Apoptose/efeitos dos fármacos , Animais , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Humanos , Nanopartículas/química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Sesquiterpenos Monocíclicos/farmacologia , Sesquiterpenos Monocíclicos/administração & dosagem , Fitol/administração & dosagem , Fitol/farmacologia , Fitol/química , Fitol/toxicidade , Linhagem Celular Tumoral , Portadores de Fármacos/química , Células A549 , Liberação Controlada de Fármacos , Sesquiterpenos/farmacologia , Sesquiterpenos/administração & dosagem , Sesquiterpenos/química , Sesquiterpenos/toxicidade , Sobrevivência Celular/efeitos dos fármacos
4.
Chem Biodivers ; 18(2): e2000897, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33410569

RESUMO

The chemical profile and phytotoxic action of Hibiscus trionum essential oil (EO) was studied. In total 17 compounds were identified via GC/MS, representing 94.18 % of the entire oil, with phytol (40.37 %) being the dominant constituent. Bioassay revealed that the EO inhibited root elongation of Medicago sativa and Amaranthus retroflexus by 32.66 % and 61.86 % at 5 mg/mL, respectively; meanwhile, the major component phytol also exhibited significant phytotoxic activity, suppressing radical elongation of Pennisetum alopecuroides, M. sativa and A. retroflexus by 26.08 %, 27.55 % and 43.96 % at 1 mg/mL, respectively. The fact that the EO showed weaker activity than phytol implied that some constituents might trigger antagonistic action to decrease the oil's activity. Our study is the first on the chemical profile and phytotoxic effect of H. trionum EO.


Assuntos
Hibiscus/química , Óleos Voláteis/química , Fitol/química , Amaranthus/efeitos dos fármacos , Amaranthus/crescimento & desenvolvimento , Cromatografia Gasosa-Espectrometria de Massas , Hibiscus/toxicidade , Medicago sativa/efeitos dos fármacos , Medicago sativa/crescimento & desenvolvimento , Óleos Voláteis/toxicidade , Fitol/toxicidade , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Testes de Toxicidade
5.
Microb Pathog ; 141: 103977, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31953226

RESUMO

Bacillus licheniformis, a pathogenic new strain of bacteria is considered as the main cause of high mortalities and economic losses among the ornamental fish farms of India. The present study aimed to investigate the anti-bacterial and Immunostimulant activity of three selected Indian medicinal plants, Allium sativum, Adhatoda vasica and Centella asiatica for treating Bacillus licheniformis PKBMS16 by subsequent experimental and clinical trials using different organic polar and non-polar solvents. The antimicrobial and Immunostimulant activity of methanolic crude extracts of Adhatoda vasica was fractions and active constituents was further characterized by chromatography and mass spectroscopy studies using FTIR, 1HNMR and 13c NMR to identify as well as to determine the nature of the pure compound which is phytol (C20H40O), a diterpene alcohol with a molecular weight of m/z 297. In order to study the in vivo anti-pathogenic influence of the biologically active compounds, phytol were incorporated to the artificial diets at the concentration of 2, 5 and 8 mg/kg and fed to the1.0 × 105 CFU/ml of Bacillus licheniformis PKBMS16 injected experimentally challenged ornamental goldfish Carassius auratus for twenty days. Phytol treated group significantly (P < 0.01 and P < 0.05) reduced the rate of fish mortality. After the termination of survivability assay the estimation of hemato-biochemical parameters have been performed and revealed the significant recovery of health condition on 20th days post treatment. Therefore, the present study concluded that the low toxicity along with high bioactivity and tolerance by lower vertebrate supports the potential of phytol as a new compound for inducing fish immunity.


Assuntos
Acanthaceae/química , Antibacterianos/farmacologia , Bacillus licheniformis/efeitos dos fármacos , Doenças dos Peixes/microbiologia , Fitol/farmacologia , Extratos Vegetais/farmacologia , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Biomarcadores , Doenças dos Peixes/tratamento farmacológico , Cromatografia Gasosa-Espectrometria de Massas , Imunomodulação/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Fitol/química , Fitol/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Espectroscopia de Infravermelho com Transformada de Fourier , Testes de Toxicidade Aguda
6.
Mar Drugs ; 17(12)2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31818004

RESUMO

Sargassum horneri, a sargassaceae brown alga, is one of the main species in the subtidal seaweeds flora extensively distributed in the Yellow and East China Sea. It has been proven that the phytosterols are an important class of bioactive substances in S. horneri. In this work, a counter-current chromatography approach is proposed for preparative separation of phytol and two analogue sterols from a crude extract of S. horneri. A two-phase solvent system composed of n-hexane-acetonitrile-methanol (5:5:6, v/v) was selected and optimized. The effects of rotary speed and flow rate on the retention of the stationary phase were carefully studied. Under the optimum conditions, phytol and two analogue sterols, fucosterol and saringosterol, were baseline separated, producing 19.8 mg phytol, 23.7 mg fucosterol, and 3.1 mg saringosterol from 300 mg of crude S. horneri extract in one-step separation. The purities of three target compounds were all above 85%. The structures of phytol and two sterols were identified by nuclear magnetic resonance spectroscopy.


Assuntos
Distribuição Contracorrente/métodos , Fitosteróis/isolamento & purificação , Sargassum/química , Espectroscopia de Ressonância Magnética , Fitol/química , Fitol/isolamento & purificação , Fitosteróis/química , Solventes/química , Estigmasterol/análogos & derivados , Estigmasterol/química , Estigmasterol/isolamento & purificação
7.
Anticancer Agents Med Chem ; 18(13): 1828-1837, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30129418

RESUMO

BACKGROUND: Phytol have various pharmacological activities such as antimicrobial, cytotoxic, antitumoral, antimutagenic, anti-atherogenic, antidiabetic, lipid-lowering, antispasmodic, antiepileptic, antinociceptive, antioxidant, anti-inflammatory, anxiolytic, antidepressant and immunoadjuvant. Several studies point to an association of phytol with implications for apoptosis and necrosis at cellular levels in cancer, yet no clear conclusions were drawn. METHOD: To clarify this, we conducted a meta-analysis of non-clinical studies of phytol and its associations with toxicity and cytotoxicity emphasizing the mechanisms of apoptosis and necrosis induction and its importance in tumor therapy. Relevant studies were systematically searched in PubMed and Web of Science. The association between phytol and cyto-/toxicity was assessed by odds ratio (ORs) and 95% confidence intervals (CI). Twentythree studies were finally included in the meta-analysis. A significant association between phytol and toxicity (OR: 1.47; 95% CI = 0.86-2.48) was found among in vivo studies and cytotoxicity (OR: 1.81; 95% CI = 1.12- 2.65, p<0.05) in in vitro and ex vivo studies. In in vitro studies, 24% of them indicate that phytol at high doses induces apoptosis by several mechanisms; while about 40% of ex vivo studies indicate that phytol induces reactive oxygen species generation. But, Phytol does not act as a direct oxidant, unlike its metabolite phytanic acid. The 24% of in vivo studies also highlighted the mechanisms for apoptosis-like including expression of Bcl2 protein or mutations in pro-apoptotic protein Bax. Of them, 8% studies show necrosis and hepatotoxicity. However, in 24% of the articles, the mechanisms of toxicity and cytotoxicity are still not well elucidated. CONCLUSION: This study confirms that the association between phytol and cyto-/toxicity depends on the dose/concentration used in the given experimental conditions. Thus, there are still great prospects for new research aimed at the use of phytol and its metabolite as anticancer agents.


Assuntos
Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Fitol/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias/patologia , Fitol/análogos & derivados , Fitol/química
8.
Chem Biol Interact ; 286: 132-140, 2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-29486182

RESUMO

Phytol (3,7,11,15-tetramethyl-2-hexadecen-1-ol) is an acyclic monounsaturated diterpene alcohol generated from chlorophyll metabolism that exerts anti-inflammatory, antithrombotic, antimicrobial, and antitumor effects. However, the effect of phytol on melanogenesis and the underlying molecular mechanisms of its inhibition remain unknown. Here, we found that phytol suppressed α-melanocyte-stimulating hormone-induced melanogenesis in B16F10 murine melanoma cells without any toxic effects. Phytol significantly attenuated melanin production by reducing the expression of tyrosinase and tyrosinase related protein 1. Treatment with phytol inhibited the expression of microphthalmia-associated transcription factor (MITF) by phosphorylating extracellular signal-regulated protein kinase (ERK). The ERK inhibitor PD98059 restored MITF expression and prevented the anti-melanogenic effect of phytol. We found that the ERK inhibitor coincidently abrogated MITF ubiquitination and degradation, suggesting that the ERK pathway is involved in phytol-induced ubiquitination of MITF. Furthermore, our data show that reactive oxygen species (ROS) production was increased in cells treated with phytol. Consistently, a ROS scavenger inhibited ERK phosphorylation and restored MITF degradation. Accordingly, the intermediary role of ROS was confirmed in phytol-induced MITF degradation. Taken together, these results demonstrate that phytol stimulates ROS production and modulates ERK-mediated proteasomal degradation of MITF in B16F10 murine melanoma cells. These findings suggest that phytol may have potential to be utilized as a whitening agent in cosmetics and as a therapy for skin hyperpigmentation.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Melaninas/biossíntese , Fator de Transcrição Associado à Microftalmia/metabolismo , Fitol/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Flavonoides/farmacologia , Expressão Gênica/efeitos dos fármacos , Camundongos , Monofenol Mono-Oxigenase/metabolismo , Fosforilação/efeitos dos fármacos , Fitol/química , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitinação/efeitos dos fármacos , alfa-MSH/farmacologia
9.
Artif Cells Nanomed Biotechnol ; 46(8): 1719-1730, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29069924

RESUMO

Alzheimer's disease (AD) is an unfavourable neurological condition of the brain leading to the loss of behavioural and cognitive skills of the aging population. At present, drugs representing cholinesterase inhibitors provide lateral side effects to AD patients. Hence, there is a need for improved fabrication of drugs without side effects, for which nanoencapsulated bioactive compounds that can cross the blood-brain barrier offer new hope as novel alternative treatment strategy for AD. This study involved synthesis of phytol loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles by solvent evaporation method. Physico-chemical characterization of phytol-PLGA NPs through the field emission scanning electron microscope, dynamic laser scattering (DLS) measurement revealed that the particles were nanosize range with smooth surface and spherical morphology. Furthermore, the biocompatibility of drug/polymer ratio was investigated by power X-ray diffraction (PXRD) and Fourier-transform infrared spectroscopic (FT-IR) analysis. The in vitro drug release study showed that the phytol was released in a sustained manner. Moreover, phytol-PLGA NPs were able to disrupt amyloid aggregates, exhibit anti-cholinesterase and anti-oxidative property and are non-cytotoxic in Neuro2a cells.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides/metabolismo , Nanopartículas , Neurônios/metabolismo , Fitol , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Agregados Proteicos/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Linhagem Celular , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Neurônios/patologia , Fitol/química , Fitol/farmacocinética , Fitol/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia
10.
Biomed Pharmacother ; 92: 491-500, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28575806

RESUMO

A number of drugs as well as lead molecules are isolated from natural sources. Phytol is one of such lead molecule belongs to terpenes group distributed widely in medicinal plants. In the present work, we investigated the cytotoxic behavior of phytol on human lung carcinoma cells (A549). Phytol was found to cause characteristic apoptotic morphological changes and generation of ROS in A549 cells. The mechanism of phytol involved the activation of TRAIL, FAS and TNF-α receptors along with caspase 9 and 3. In silico molecular docking studies revealed that phytol has a good binding affinity with glucose-6-phosphate dehydrogenase (G6PD), which is known to promote tumor proliferation. The ability of phytol to become potential drug candidate has been revealed from the pharmacokinetic study performed in the present study.


Assuntos
Caspase 3/biossíntese , Caspase 9/biossíntese , Glucosefosfato Desidrogenase/metabolismo , Neoplasias Pulmonares/metabolismo , Fitol/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Células A549 , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Linhagem Celular Tumoral , Indução Enzimática/efeitos dos fármacos , Indução Enzimática/fisiologia , Humanos , Fitol/química , Fitol/uso terapêutico , Estrutura Secundária de Proteína , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Receptor fas/metabolismo
11.
Molecules ; 21(6)2016 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-27338332

RESUMO

The chemical composition of volatile oils from 22 genotypes of Citrus and related genera was poorly differentiated, but chemometric techniques have clarified the relationships between the 22 genotypes, and allowed us to understand their resistance to D. citri. The most convincing similarities include the synthesis of (Z)-ß-ocimene and (E)-caryophyllene for all 11 genotypes of group A. Genotypes of group B are not uniformly characterized by essential oil compounds. When stimulated with odor sources of 22 genotypes in a Y-tube olfactometer D. citri preferentially entered the arm containing the volatile oils of Murraya paniculata, confirming orange jasmine as its best host. C. reticulata × C. sinensis was the least preferred genotype, and is characterized by the presence of phytol, (Z)-ß-ocimene, and ß-elemene, which were not found in the most preferred genotype. We speculate that these three compounds may act as a repellent, making these oils less attractive to D. citri.


Assuntos
Citrus/efeitos dos fármacos , Hemípteros/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Animais , Brasil , Citrus/genética , Citrus/parasitologia , Genótipo , Hemípteros/patogenicidade , Repelentes de Insetos/química , Repelentes de Insetos/farmacologia , Óleos Voláteis/química , Fitol/química , Fitol/farmacologia , Óleos de Plantas/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia
12.
Z Naturforsch C J Biosci ; 71(3-4): 39-43, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26927220

RESUMO

The phytochemical study of the leaves, roots, and flowers of Palicourea rigida led to the isolation of the triterpenes betulinic acid (1) and lupeol (2), the diterpene phytol (3), and the iridoid glycosides sweroside (4) and secoxyloganin (5). These compounds were identified using NMR 1H and 13C and comparing the spectra with published data. We studied the antiedematogenic activity of crude extracts from the organs, and of different fractions, in mice and found that the n-hexane fraction of the leaf extract significantly inhibited the ear edema resulting from croton oil administration. The crude extract from leaves was not acutely toxic to the mice.


Assuntos
Edema/prevenção & controle , Extratos Vegetais/farmacologia , Rubiaceae/química , Testes de Toxicidade Aguda/métodos , Animais , Flores/química , Glucosídeos Iridoides/química , Glucosídeos Iridoides/farmacologia , Espectroscopia de Ressonância Magnética/métodos , Camundongos , Estrutura Molecular , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/farmacologia , Fitol/química , Fitol/farmacologia , Fitoterapia , Extratos Vegetais/química , Folhas de Planta/química , Raízes de Plantas/química , Resultado do Tratamento , Triterpenos/química , Triterpenos/farmacologia , Ácido Betulínico
13.
Pharm Biol ; 54(10): 2073-81, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26933930

RESUMO

Context Gelidiella acerosa (Forsskål) Feldmann & G. Hamel (Rhodophyta-Gelidiales) is a marine red macroalga. Our previous work found that a benzene extract of G. acerosa possesses noticeable neuroprotective activity, when evaluated through in vitro and in vivo systems. Objective Bioactive-guided fractionation and identification of active compounds by column chromatography using solvents of varying polarity. Materials and methods Fractionation was done by column chromatography, antioxidant and anticholinesterase activity was assessed by DPPH and cholinesterase inhibition assays (50-200 µg/ml), compound identification was done by LC-MS analysis, the mode of interaction of active compound was analyzed through docking studies and quantification was done by high-performance thin-layer chromatography (HPTLC) analysis. Results The results suggest that fractions F9-F13 exhibited significant (p < 0.05) antioxidant and anticholinesterase activities. Hence, these fractions were pooled together and verified for neuroprotective activity. The pooled fraction was subjected to LC-MS analysis and among all the compounds, phytol was previously reported to possess excellent neuroprotective potential. Hence, the neuroprotective potential of phytol was assessed. The results suggest that phytol showed significant (p < 0.05) antioxidant activities (25-125 µg/ml) with an IC50 value of 95.27 ± 1.65 µg/ml and cholinesterase inhibitory potential (5-25 µg/ml) with IC50 values of 2.704 ± 0.07 and 5.798 ± 0.72 µg/ml for AChE and BuChE, respectively. Molecular docking studies suggest that phytol interacts with cholinesterase through the arginine residue of the enzyme. HPTLC quantification showed that about 6.266 µg of phytol was present per mg of pooled fraction. Conclusion The study suggests that phytol might act as the key compound in contributing to the neuroprotective potential of G. acerosa.


Assuntos
Antioxidantes/isolamento & purificação , Fracionamento Químico/métodos , Inibidores da Colinesterase/isolamento & purificação , Microalgas/química , Fármacos Neuroprotetores/isolamento & purificação , Fitol/isolamento & purificação , Rodófitas/química , Acetilcolinesterase/metabolismo , Antioxidantes/química , Antioxidantes/farmacologia , Compostos de Bifenilo/química , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Cromatografia Líquida , Cromatografia em Camada Fina , Relação Dose-Resposta a Droga , Espectrometria de Massas , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Fitol/química , Fitol/farmacologia , Picratos/química , Solventes/química
14.
Nat Prod Res ; 30(7): 853-6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26214127

RESUMO

The present study aimed to analyse the chemical components of the essential oil from Pyrrosia tonkinensis by GC-MS and evaluate the in vitro antibacterial activity. Twenty-eight compounds, representing 88.1% of the total essential oil, were identified and the major volatile components were trans-2-hexenal (22.1%), followed by nonanal (12.8%), limonene (9.6%), phytol (8.4%), 1-hexanol (3.8%), 2-furancarboxaldehyde (3.5%) and heptanal (3.1%). The antibacterial assays showed that the essential oil of P. tonkinensis had good antibacterial activities against all the tested microorganisms. This paper first reported the chemical composition and antimicrobial activity of the essential oil from P. tonkinensis.


Assuntos
Antibacterianos/isolamento & purificação , Óleos Voláteis/química , Óleos de Plantas/química , Polypodiaceae/química , Aldeídos/química , Aldeídos/isolamento & purificação , Antibacterianos/química , Cicloexenos/química , Cicloexenos/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Hexanóis/química , Hexanóis/isolamento & purificação , Limoneno , Testes de Sensibilidade Microbiana , Fitol/química , Fitol/isolamento & purificação , Terpenos/química , Terpenos/isolamento & purificação
15.
Plant Cell ; 27(10): 2846-59, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26452599

RESUMO

Phytol from chlorophyll degradation can be phosphorylated to phytyl-phosphate and phytyl-diphosphate, the substrate for tocopherol (vitamin E) synthesis. A candidate for the phytyl-phosphate kinase from Arabidopsis thaliana (At1g78620) was identified via a phylogeny-based approach. This gene was designated VITAMIN E DEFICIENT6 (VTE6) because the leaves of the Arabidopsis vte6 mutants are tocopherol deficient. The vte6 mutant plants are incapable of photoautotrophic growth. Phytol and phytyl-phosphate accumulate, and the phytyl-diphosphate content is strongly decreased in vte6 leaves. Phytol feeding and enzyme assays with Arabidopsis and recombinant Escherichia coli cells demonstrated that VTE6 has phytyl-P kinase activity. Overexpression of VTE6 resulted in increased phytyl-diphosphate and tocopherol contents in seeds, indicating that VTE6 encodes phytyl-phosphate kinase. The severe growth retardation of vte6 mutants was partially rescued by introducing the phytol kinase mutation vte5. Double mutant plants (vte5 vte6) are tocopherol deficient and contain more chlorophyll, but reduced amounts of phytol and phytyl-phosphate compared with vte6 mutants, suggesting that phytol or phytyl-phosphate are detrimental to plant growth. Therefore, VTE6 represents the missing phytyl-phosphate kinase, linking phytol release from chlorophyll with tocopherol synthesis. Moreover, tocopherol synthesis in leaves depends on phytol derived from chlorophyll, not on de novo synthesis of phytyl-diphosphate from geranylgeranyl-diphosphate.


Assuntos
Arabidopsis/metabolismo , Fitol/metabolismo , Tocoferóis/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Transporte Biológico , Vias Biossintéticas , Clorofila/metabolismo , Difosfatos/química , Difosfatos/metabolismo , Mutação , Fosforilação , Fosfotransferases/genética , Fosfotransferases/metabolismo , Filogenia , Fitol/química , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Tocoferóis/química
16.
Chem Biol Interact ; 240: 60-73, 2015 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-26296761

RESUMO

This study aims to review phytol (PYT), through published articles, periodicals, magazines and patents, which were retrieved from the PM, SD, WS, SP; DII, WIPO, CIPO, USPTO and INPI databases. Among the 149 articles and 62 patents, 27.52% articles and 87.09% patients were found on the searched topic, PYT and its sources and synthesis and metabolism; then followed by 15.44% and 14.77% articles on PYT in cytotoxicity/cancer/mutagenicity/teratogenicity and PYT in neurological diseases, respectively. In the pharma-medico viewpoint, PYT and its derivatives have been evident to have antimicrobial, cytotoxic, antitumorous, antimutagenic, anti-teratogenic, antibiotic-chemotherapeutic, antidiabetic, lipid lowering, antispasmodic, anticonvulsant, antinociceptive, antioxidant, anti-inflammatory, anxiolytic, antidepressant, immunoadjuvancy, hair growth facilitator, hair fall defense and antidandruff activities. Otherwise, the important biometebolite of PYT is phytanic acid (PA). Evidence shows PA to have cytotoxic, anticancer, antidiabetic, lipid lowering and aniteratogenic activities. In addition, it may be considered as an important biomarker for some diseases such as Refsum's Disease (RD), Sjögren Larsson syndrome (SLS), rhizomelic chondrodysplasia punctata (RZCP), chronic polyneuropathy (CP), Zellweger's disease hyperpipecolic academia (ZDHA) and related diseases. Thus, phytol may be considered as a new drug candidate.


Assuntos
Química Farmacêutica , Fitol/química , Fitol/farmacologia , Bases de Dados como Assunto , Humanos , Patentes como Assunto
17.
Chem Biodivers ; 12(8): 1172-83, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26265569

RESUMO

Stachys annua subsp. annua, well-known in central Italy as 'stregona annuale', is an annual, small, slightly-scented herb, commonly found in fields and uncultivated areas in almost all regions of Italy. In folk medicine, its aerial parts were used as anti-catarrhal, febrifuge, tonic, and vulnerary. In the present work, the chemical composition of the flowering aerial parts was studied. The hydrodistilled volatile oil, analysed by GC/MS, showed sesquiterpenoids as the major fraction (42.5%); phytol (9.8%), germacrene D (9.2%), and spathulenol (8.5%) were the most abundant constituents. The volatile oil was assayed for antioxidant and cytotoxic activity by DPPH, ABTS, FRAP, and MTT methods. The cytotoxicity results against HCT116, A375, and MDA-MB 231 human tumor cell lines were significant, with IC50 values of 23.5, 37.2, and 41.5 µg/ml, respectively, whereas the antioxidant power was negligible. The EtOH extract was composed mainly of three glycosidic flavonoids, namely 7-{[2-O-(6-O-acetyl-ß-D-allopyranosyl)-ß-D-glucopyranosyl]oxy}-5,8-dihydroxy-2-(4-methoxyphenyl)-4H-1-benzopyran-4-one (1), 7-{[6-O-acetyl-2-O-(6-O-acetyl-ß-D-allopyranosyl)-ß-D-glucopyranosyl]oxy}-2-(3,4-dihydroxyphenyl)-5,8-dihydroxy-4H-1-benzopyran-4-one (2), and 7-{[6-O-acetyl-2-O-(ß-D-allopyranosyl)-ß-D-glucopyranosyl]oxy}-2-(3-hydroxy-4-methoxyphenyl)-5,8-dihydroxy-4H-1-benzopyran-4-one (3). On the contrary, iridoids, considered chemotaxonomic markers of the genus Stachys, were absent in this species. Finally, the morphological and histochemical survey showed that glandular trichomes were composed of two main types, i.e. peltate type A and capitate types B and C giving positive response for both lipids and polyphenols.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Stachys/química , Linhagem Celular Tumoral , Flores/química , Humanos , Itália , Neoplasias/tratamento farmacológico , Fitol/química , Fitol/farmacologia , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/farmacologia , Tricomas/química , Tricomas/ultraestrutura
19.
Environ Sci Pollut Res Int ; 22(19): 14793-800, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25989859

RESUMO

The hexane and ether extracts of leaves, bark and roots of Jatropha curcas were screened for their toxicity against different developmental stages of housefly. The larvicidal, pupicidal and adulticidal activities were analysed at various concentrations (0.78-7.86 mg/cm(2)) of hexane and ether extracts. The lethal concentration values (LC50) of hexane extract of J. curcas leaves were 3.0 and 0.27 mg/cm(2) for adult and larval stages of housefly, respectively, after 48 h. Similarly, the ether extract of leaf showed the LC50 of 2.20 and 4.53 mg/cm(2) for adult and larval stages of housefly. Least toxicity was observed with hexane root extract of J. curcas with LC50 values of 14.18 and 14.26 mg/cm(2) for adult and larvae of housefly, respectively, after 48 h. The variation in LC50 against housefly pupae was found to be 8.88-13.10 mg/cm(2) at various J. curcas extract concentrations. The GC-MS analysis of J. curcas leaf extract revealed the presence of trans-phytol (60.81 %), squalene (28.58 %), phytol (2.52 %) and nonadecanone (1.06 %) as major components that could be attributed for insecticidal activity of J. curcas extracts.


Assuntos
Moscas Domésticas/efeitos dos fármacos , Inseticidas/farmacologia , Jatropha/química , Extratos Vegetais/farmacologia , Animais , Ácidos Graxos/química , Ácidos Graxos/isolamento & purificação , Inseticidas/química , Inseticidas/isolamento & purificação , Larva/efeitos dos fármacos , Dose Letal Mediana , Fitol/química , Fitol/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Raízes de Plantas/química , Pupa/efeitos dos fármacos , Esqualeno/química , Esqualeno/isolamento & purificação
20.
Plant Physiol Biochem ; 91: 56-60, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25885355

RESUMO

The independent and interactive effects of solar ultraviolet-B radiation (UV-B), moderate water deficit and sprayed abscisic acid (ABA) on leaves gas exchange and biochemical aspects of field-grown grapevines of the cv. Malbec were investigated in a high altitude vineyard (1450 m a.s.l.). Two UV-B treatments (ambient solar UV-B or reduced UV-B), two watering treatments (well watered or moderate water deficit) and two ABA treatments (no ABA and sprayed ABA) were given alone and combined in a factorial design. Gas exchange and photosynthesis were reduced by water deficit and highly impaired in the UV-B and water deficit combined treatment. UV-absorbing compounds were stimulated independently by UV-B. The monoterpenes α-pinene, 3-carene and terpinolene, and the sesquiterpene nerolidol were augmented by UV-B, water deficit or sprayed ABA. Levels of the triterpene squalene and the diterpene phytol were significantly higher in the treatment that combined UV-B, water deficit and ABA applications. Environment signals (solar UV-B and moderate water deficit) and sprayed ABA elicited mechanisms of acclimation by augmenting the content of terpenes with antioxidant and antifungal properties, thus enhancing the plant defensive mechanisms towards signals both biotic and abiotic.


Assuntos
Ácido Abscísico/química , Aclimatação/efeitos dos fármacos , Folhas de Planta/fisiologia , Luz Solar , Vitis/fisiologia , Água/fisiologia , Antioxidantes/química , Monoterpenos Bicíclicos , Clorofila/química , Monoterpenos Cicloexânicos , Gases , Monoterpenos/química , Fotossíntese , Fitol/química , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/efeitos da radiação , Sesquiterpenos/química , Terpenos/química , Raios Ultravioleta , Vitis/efeitos dos fármacos , Vitis/efeitos da radiação , Ácido alfa-Linolênico/química
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