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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.
J Sci Food Agric ; 104(12): 7536-7549, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38747177

RESUMO

BACKGROUND: To improve phytol bioavailability, a novel method of magnetic stirring and high-pressure homogenization (HPH) combination was used to prepare zein/fucoidan-coated phytol nanoliposomes (P-NL-ZF). The characterization, the simulated in vitro digestion, and the antioxidant activity of these phytol nanoliposomes from the different processes have been studied. RESULTS: Based on the results of dynamic light scattering (DLS) and gas chromatography-mass spectrometer (GC-MS) analysis, P-NL-ZF prepared through the combination of magnetic stirring and HPH exhibited superior encapsulation efficiency at 76.19% and demonstrated exceptional physicochemical stability under a series of conditions, including storage, pH, and ionic in comparison to single method. It was further confirmed that P-NL-ZF by magnetic stirring and HPH displayed a uniform distribution and regular shape through transmission electron microscopy (TEM). Fourier-transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) analysis showed that electrostatic interactions and hydrogen bonding were the primary driving forces for the formation of composite nanoliposomes. Additionally, an in vitro digestion study revealed that multilayer composite nanoliposomes displayed significant and favorable slow-release properties (58.21%) under gastrointestinal conditions compared with traditional nanoliposomes (82.36%) and free phytol (89.73%). The assessments of chemical and cell-based antioxidant activities demonstrated that the coating of zein/fucoidan on phytol nanoliposomes resulted in enhanced effectiveness in scavenging activity of ABTS free radical and hydroxyl radical and mitigating oxidative damage to HepG2 cells. CONCLUSION: Based on our studies, the promising delivery carrier of zein/fucoidan-coated nanoliposomes is contributed to the encapsulation of hydrophobic natural products and enhancement of their biological activity. © 2024 Society of Chemical Industry.


Assuntos
Antioxidantes , Lipossomos , Nanopartículas , Fitol , Zeína , Antioxidantes/química , Antioxidantes/farmacologia , Lipossomos/química , Zeína/química , Fitol/química , Nanopartículas/química , Humanos , Tamanho da Partícula , Estabilidade de Medicamentos , Composição de Medicamentos/métodos , Polissacarídeos/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos
3.
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
4.
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
5.
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
6.
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
7.
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
8.
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
9.
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
10.
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
11.
Biochem Biophys Res Commun ; 452(4): 873-80, 2014 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-25157808

RESUMO

Galactosylglycerolipids (GGLs) and chlorophyll are characteristic components of chloroplast in photosynthetic organisms. Although chlorophyll is anchored to the thylakoid membrane by phytol (tetramethylhexadecenol), this isoprenoid alcohol has never been found as a constituent of GGLs. We here described a novel GGL, in which phytol was linked to the glycerol backbone via an ether linkage. This unique GGL was identified as an Alkaline-resistant and Endogalactosylceramidase (EGALC)-sensitive GlycoLipid (AEGL) in the marine green alga, Ulva pertusa. EGALC is an enzyme that is specific to the R-Galα/ß1-6Galß1-structure of galactolipids. The structure of U. pertusa AEGL was determined following its purification to 1-O-phytyl-3-O-Galα1-6Galß1-sn-glycerol by mass spectrometric and nuclear magnetic resonance analyses. AEGLs were ubiquitously distributed in not only green, but also red and brown marine algae; however, they were rarely detected in terrestrial plants, eukaryotic phytoplankton, or cyanobacteria.


Assuntos
Éteres/química , Galactolipídeos/química , Fitol/química , Extratos Vegetais/química , Ulva/química , Reagentes de Ligações Cruzadas/química , Reagentes de Ligações Cruzadas/isolamento & purificação , Éteres/isolamento & purificação , Galactolipídeos/isolamento & purificação , Fitol/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Especificidade da Espécie , Ulva/classificação
12.
Zhong Yao Cai ; 37(4): 616-20, 2014 Apr.
Artigo em Zh | MEDLINE | ID: mdl-25345137

RESUMO

OBJECTIVE: To analyze the chemical compositions of Pandanus amaryllifolius leaves essential oil extracted by steam distillation. METHODS: The essential oil of Pandanus amaryllifolius leaves was analyzed by gas chromatography-mass spectrum, and the relative content of each component was determined by area normalization method. RESULTS: 128 peaks were separated and 95 compounds were identified, which weighed 97.75%. The main chemical components of the essential oil were phytol (42.15%), squalene (16.81%), what's more pentadecanal (6.17%), pentadecanoic acid (4.49%), 3, 7, 11, 15-tetramethyl-2-hexadecen-1-ol (3.83%), phytone (2.05%) and the other 74 chemical compositions were firstly identified from the essential oil of Pandanus amaryllifolius leaves. CONCLUSION: The chemical compositions of Pandanu samaryllifolius leaves essential oil was systematically, deeply isolated and identified for the first time. This experiment has provided scientific foundation for further utilization of Pandanus amaryllifolius leaves.


Assuntos
Óleos Voláteis/química , Pandanaceae/química , Fitol/análise , Folhas de Planta/química , Esqualeno/análise , Aldeídos/análise , Aldeídos/química , Destilação , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Ácidos Graxos/análise , Ácidos Graxos/química , Cromatografia Gasosa-Espectrometria de Massas , Estrutura Molecular , Óleos Voláteis/isolamento & purificação , Fitol/química , Esqualeno/química , Vapor
13.
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
14.
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
15.
Chem Biodivers ; 10(12): 2209-20, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24327441

RESUMO

The cancerostatic 5-fluorouridine (5-FUrd; 1) was sequentially sugar-protected by introduction of a 2',3'-O-heptylidene ketal group (→2), followed by 5'-O-monomethoxytritylation (→3). This fully protected derivative was submitted to Mitsunobu reactions with either phytol ((Z and E)-isomer) or nerol ((Z)-isomer) to yield the nucleoterpenes 4a and 4b. Both were 5'-O-deprotected with 2% Cl2 CHCOOH in CH2 Cl2 to yield compounds 5a and 5b, respectively. These were converted to the 5'-O-cyanoethyl phosphoramidites 6a and 6b, respectively. Moreover, the 2',3'-O-(1-nonyldecylidene) derivative, 7a, of 5-fluorouridine was resynthesized and labelled at C(5') with an Eterneon-480 fluorophor(®) (→7b). The resulting nucleolipid was studied with respect to its incorporation in an artificial bilayer, as well as to its aggregate formation. Additionally, two oligonucleotides carrying terminal phytol-alkylated 5-fluorouridine tags were prepared, one of which was studied concerning its incorporation in an artificial lipid bilayer.


Assuntos
Materiais Biocompatíveis/química , DNA/metabolismo , Fitol/química , Terpenos/química , Uridina/análogos & derivados , Monoterpenos Acíclicos , Materiais Biocompatíveis/metabolismo , DNA/química , Isomerismo , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Oligonucleotídeos/química , Oligonucleotídeos/metabolismo , Uridina/síntese química , Uridina/química
16.
Zhong Yao Cai ; 36(4): 575-7, 2013 Apr.
Artigo em Zh | MEDLINE | ID: mdl-24134005

RESUMO

OBJECTIVE: To analyze the volatile components from flowers of Gymnema sylvestre. METHODS: Volatile components of flowers of Gymnema sylvestre were extracted by water vapor distilling, and the components were separated and identified by GC-MS. RESULTS: 55 components were separated and 33 components were identified, accounting for 88.73% of all quantity. The principal volatile components are Phytol, Pentacosane, 10-Heneicosene (c, t), 3-Eicosene, (E) -and 2-Methyl-Z-2-docosane. CONCLUSION: The research can pro-vide scientific basis for chemical component research of flowers of Gymnema sylvestre.


Assuntos
Flores/química , Gymnema sylvestre/química , Compostos Orgânicos Voláteis/química , Alcanos/química , Cromatografia Gasosa-Espectrometria de Massas , Estrutura Molecular , Fitol/química , Vapor , Compostos Orgânicos Voláteis/isolamento & purificação
17.
Biochim Biophys Acta ; 1811(9): 498-507, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21683154

RESUMO

Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is a branched-chain fatty acid which cannot be beta-oxidized due to the presence of the first methyl group at the 3-position. Instead, phytanic acid undergoes alpha-oxidation to produce pristanic acid (2,6,10,14-tetramethylpentadecanoic acid) plus CO(2). Pristanic acid is a 2-methyl branched-chain fatty acid which can undergo beta-oxidation via sequential cycles of beta-oxidation in peroxisomes and mitochondria. The mechanism of alpha-oxidation has been resolved in recent years as reviewed in this paper, although some of the individual enzymatic steps remain to be identified. Furthermore, much has been learned in recent years about the permeability properties of the peroxisomal membrane with important consequences for the alpha-oxidation process. Finally, we present new data on the omega-oxidation of phytanic acid making use of a recently generated mouse model for Refsum disease in which the gene encoding phytanoyl-CoA 2-hydroxylase has been disrupted.


Assuntos
Ácido Fitânico/metabolismo , Animais , Transporte Biológico , Dieta , Humanos , Estrutura Molecular , Oxirredução , Peroxissomos/enzimologia , Ácido Fitânico/química , Fitol/química , Fitol/metabolismo , Doença de Refsum/metabolismo , Doença de Refsum/fisiopatologia
18.
J Chem Ecol ; 37(4): 360-3, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21465267

RESUMO

Hexahydrofarnesylacetone (6,10,14-trimethylpentadecan-2-one, 1) is a widespread ketone occurring in plants and insects. Several species use this compound or the respective alcohol as part of their pheromone bouquet. Here, we showed by using deuterium labeled phytol (3) and GC-MS experiments that the Large Cabbage White butterfly Pieris brassicae can take up phytol in the larval stage and transforms it into 1 by oxidative degradation.


Assuntos
Fitol/química , Terpenos/metabolismo , Animais , Borboletas , Deutério/química , Cromatografia Gasosa-Espectrometria de Massas , Larva/metabolismo , Masculino , Oxirredução , Feromônios/metabolismo
19.
Planta Med ; 77(1): 22-6, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20645242

RESUMO

The anti-scratching behavioral effect of the essential oil and phytol isolated from Artemisia princeps Pamp. (AP, family Asteraceae), which is widely used in traditional medicine for inflammatory diseases, was investigated IN VIVO. Treatment of mice with AP essential oil (APEO) and phytol inhibited histamine- and compound 48/80-induced scratching behaviors. The anti-scratching behavioral effects of APEO and phytol are in proportion to their vascular permeability-inhibitory effects. These agents also inhibited the level of allergic cytokines, IL-4, and TNF- α, and the activation of transcription factors, NF- κB and c-jun (AP-1), in histamine-treated skin tissues. Based on these results, APEO and phytol may improve scratching behavior in skin by inhibiting the expression of allergic cytokines via the regulation of NF- κB and AP-1 activation.


Assuntos
Antipruriginosos/farmacologia , Asteraceae/química , Óleos Voláteis/farmacologia , Fitol/farmacologia , Óleos de Plantas/farmacologia , Prurido/tratamento farmacológico , Animais , Antipruriginosos/química , Antipruriginosos/uso terapêutico , Ativação Enzimática/efeitos dos fármacos , Interleucina-4/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Óleos Voláteis/química , Óleos Voláteis/uso terapêutico , Fitol/química , Fitol/uso terapêutico , Óleos de Plantas/química , Óleos de Plantas/uso terapêutico , Fator de Transcrição AP-1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
20.
Zhong Yao Cai ; 34(9): 1379-83, 2011 Sep.
Artigo em Zh | MEDLINE | ID: mdl-22260006

RESUMO

OBJECTIVE: To compare volatile oil of Lonicera confusa (red gland Lonicera) fresh leaves with dry leaves and provide evidence for further study of Lonicera confusa leaves. METHODS: GC-MS was used to identify chemical composition in volatile oil in red gland Lonicera leaves. RESULTS: 93 chemical components were separated in fresh leaves in which 39 chemical components were identified; 88 chemical components were separated in dry leaves in which 51 chemical components were identified. The main components of fresh leaves of red gland Lonicera were n-Hexadecanoic acid (11.90%), Phytol (11.79) and 9,12,15-Octadecatrienoic acid, methyl ester, (Z, Z, Z)(7.08); The main components of dry leaves of red gland Lonicera were 1,6-Octadien-3-ol, 3,7-dimethyl-(27.62%), Phytol (7.57%) and 2, 6, 10, 14, 18, 22-Tetracosahexaene, 2, 6, 10, 15, 19, 23-hexamethyl-, (all-E) (4.70%). CONCLUSION: There are significant differences between volatile oil between fresh and dry leaves.


Assuntos
Lonicera/química , Óleos Voláteis/química , Ácido Palmítico/análise , Folhas de Planta/química , China , Cromatografia Gasosa-Espectrometria de Massas/métodos , Óleos Voláteis/análise , Óleos Voláteis/isolamento & purificação , Ácido Palmítico/química , Fitol/análise , Fitol/química , Plantas Medicinais/química , Vapor
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