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1.
Biochem J ; 481(4): 279-293, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38314636

RESUMO

Tocopherols are lipophilic antioxidants known as vitamin E and synthesized from the condensation of two metabolic pathways leading to the formation of homogentisate and phytyl diphosphate. While homogentisate is derived from tyrosine metabolism, phytyl diphosphate may be formed from geranylgeranyl diphosphate or phytol recycling from chlorophyll degradation. Here, we hypothesized that abscisic acid (ABA) could induce tocopherol biosynthesis in sweet cherries by modifying the expression of genes involved in vitamin E biosynthesis, including those from the phytol recycling pathway. Hence, the expression of key tocopherol biosynthesis genes was determined together with vitamin E and chlorophyll contents during the natural development of sweet cherries on the tree. Moreover, the effects of exogenously applied ABA on the expression of key tocopherol biosynthesis genes were also investigated during on-tree fruit development, and tocopherols and chlorophylls contents were analyzed. Results showed that the expression of tocopherol biosynthesis genes, including VTE5, VTE6, HPPD and HPT showed contrasting patterns of variation, but in all cases, increased by 2- and 3-fold over time during fruit de-greening. This was not the case for GGDR and VTE4, the first showing constitutive expression during fruit development and the second with marked down-regulation at ripening onset. Furthermore, exogenous ABA stimulated the production of both α- and γ-tocopherols by 60% and 30%, respectively, promoted chlorophyll degradation and significantly enhanced VTE5 and VTE6 expression, and also that of HPPD and VTE4, altogether increasing total tocopherol accumulation. In conclusion, ABA increases promote the transcription of phytol recycling enzymes, which may contribute to vitamin E biosynthesis during fruit development in stone fruits like sweet cherries.


Assuntos
Difosfatos , Prunus avium , Vitamina E , Vitamina E/metabolismo , Frutas , Prunus avium/metabolismo , Ácido Abscísico/metabolismo , Tocoferóis/metabolismo , Clorofila/metabolismo , Fitol/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
2.
Anal Bioanal Chem ; 416(11): 2809-2818, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38189919

RESUMO

In this study, arsenic (As) speciation was investigated in the freshwater alga Chlamydomonas reinhardtii treated with 20 µg/L arsenate using fractionation as well as ICP-MS/ESI-MS analyses and was compared with the known As metabolite profile of wild-grown Saccharina latissima. While the total As accumulation in C. reinhardtii was about 85% lower than in S. latissima, the relative percentage of arsenolipids was significantly higher in C. reinhardtii (57.0% vs. 5.01%). As-containing hydrocarbons and phospholipids dominated the hydrophobic As profile in S. latissima, but no As-containing hydrocarbons were detectable in C. reinhardtii. Instead for the first time, an arsenoriboside-containing phytol (AsSugPhytol) was found to dominate the hydrophobic arsenicals of C. reinhardtii. Interestingly, this compound and its relatives had so far been only found in green marine microalgae, open sea plankton (mixed assemblage), and sediments but not in brown or red macroalgae. This compound family might therefore relate to differences in the arsenic metabolism between the algae phyla.


Assuntos
Arsênio , Arsenicais , Chlamydomonas reinhardtii , Algas Comestíveis , Laminaria , Arsenicais/química , Arsênio/metabolismo , Chlamydomonas reinhardtii/metabolismo , Hidrocarbonetos
3.
Biochem Genet ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570442

RESUMO

The present study was aimed at the evaluation of neuroprotective ability of methanolic extract of Trianthema decandra (METD) against hyperglycemia-related cognitive impairment in rats. The extract of T. decandra was standardized by TLC and HPTLC methods. To verify the identity and purity of isolated compounds, they were segregated and characterized using various techniques, including UV-visible spectrophotometry, FT-IR, H-NMR, and Mass spectroscopy. α-Amylase and α-glucosidase inhibition property of the extracts were assessed in-vitro. The screening of the neuroprotective effects of METD in hyperglycemic rats was done utilizing Morri's water (MWM) and elevated plus maze (EPM) model, as well as acetylcholinesterase (AChE) activity. The extracts of Trianthema decandra and its chemical constituents, namely quercetin and phytol, demonstrated a significant protective effect on enzymes like α-amylase and α-glucosidase. Methanol and hydroalcoholic extracts have shown the strongest inhibitory activity followed by chloroform extract. Quercetin and phytol were associated with the methanolic and chloroform extracts which were identified using TLC and HPTLC techniques. During the thirty days of the study, the induction of diabetes in the rats exhibited persistent hyperglycemia, hyperlipidemia, higher escape latency during training trials and reduced time spent in target quadrant in probe trial in Morris water maze test, and increased escape latency in EPM task. Regimen of METD (200 and 400 mg/kg) in the diabetic rats reduced the glucose levels in blood, lipid, and liver profile and showed positive results on Morri's water and elevated plus maze tasks. During the investigation, it was determined that Trianthema decandra extracts and the chemical constituent's quercetin and phytol in it had anti-diabetic and neuroprotective activities.

4.
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
5.
Plant J ; 109(5): 1290-1304, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34902195

RESUMO

During chlorophyll degradation, large amounts of the isoprenoid alcohol phytol are released. The pathway of phytol catabolism has been studied in humans, because chlorophyll is part of the human diet, but little is known for plants. In humans, phytanoyl-CoA derived from phytol is degraded via α-oxidation by phytanoyl-CoA hydroxylase (PAHX) and 2-hydroxy-phytanoyl-CoA lyase (HPCL). Arabidopsis contains two sequences homologous to the human proteins AtPAHX and AtHPCL. Insertional mutants of Arabidopsis (pahx, hpcl) were grown under N deprivation to stimulate chlorophyll breakdown or supplemented with phytol to increase the endogenous amount of phytol. During N deprivation, chlorophyll, phytol, phytenal, upstream metabolites of phytol breakdown, and tocopherol and fatty acid phytyl esters, alternative phytol-derived lipids, accumulated in pahx and hpcl mutants, in line with the scenario that the mutations interfere with phytol degradation. AtHPCL was localized to the peroxisomes. Expression analysis of the AtHPCL sequence in the yeast Δpxp1 or Δmpo1 mutants followed by supplementation with 2-hydroxy-palmitic acid and enzyme assays of peroxisomal proteins from Col-0 and hpcl plants with 2-hydroxy-stearoyl-CoA revealed that AtHPCL harbors 2-hydroxy-acyl-CoA lyase activity. The α-dioxygenases αDOX1 and αDOX2 are involved in α-oxidation of fatty acids and could be involved in an alternative pathway of phytol degradation. However, phytol-related lipids in the αdox1, αdox2, or αdox1 αdox2 mutants were not altered compared with Col-0, indicating that αDOX1 and αDOX2 are not involved in phytol degradation. These results demonstrate that phytol degradation in Arabidopsis involves α-oxidation by AtPAHX and AtHPCL, but that it is independent of αDOX1/αDOX2.


Assuntos
Arabidopsis , Liases , Arabidopsis/genética , Arabidopsis/metabolismo , Clorofila/metabolismo , Coenzima A/metabolismo , Ácidos Graxos/metabolismo , Liases/metabolismo , Ácido Fitânico/análogos & derivados , Fitol/metabolismo
6.
Plant Mol Biol ; 111(4-5): 365-378, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36587296

RESUMO

Tocopherols are potent membrane-bound antioxidant molecules that are paramount for plant physiology and also important for human health. In the past years, chlorophyll catabolism was identified as the primary source of phytyl diphosphate for tocopherol synthesis by the action of two enzymes, PHYTOL KINASE (VTE5) and PHYTHYL PHOSPHATE KINASE (VTE6) that are able to recycle the chlorophyll-derived phytol. While VTE5 and VTE6 were proven essential for tocopherol metabolism in tomato fruits, it remains unknown whether they are rate-limiting steps in this pathway. To address this question, transgenic tomato plants expressing AtVTE5 and AtVTE6 in a fruit-specific manner were generated. Although ripe transgenic fruits exhibited higher amounts of tocopherol, phytol recycling revealed a more intimate association with chlorophyll than with tocopherol content. Interestingly, protein-protein interactions assays showed that VTE5 and VTE6 are complexed, channeling free phytol and phytyl-P, thus mitigating their cytotoxic nature. Moreover, the analysis of tocopherol accumulation dynamics in roots, a chlorophyll-devoid organ, revealed VTE5-dependent tocopherol accumulation, hinting at the occurrence of shoot-to-root phytol trafficking. Collectively, these results demonstrate that phytol recycling is essential for tocopherol biosynthesis, even in chlorophyll-devoid organs, yet it is not the rate-limiting step for this pathway under normal growth conditions.


Assuntos
Solanum lycopersicum , Tocoferóis , Humanos , Tocoferóis/metabolismo , Frutas/metabolismo , Fitol/metabolismo , Clorofila/metabolismo , Plantas Geneticamente Modificadas/metabolismo
7.
Chem Biodivers ; 20(4): e202201045, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36811152

RESUMO

Cestrum diurnum L. (Solanaceae) is a fragrant ornamental tree cultivated in different parts around the world. In this study, the essential oil (EO) of the aerial parts was extracted by hydrodistillation (HD), steam distillation (SD) and microwave-assisted hydro-distillation (MAHD). GC/MS analysis of the three EOs revealed that phytol represents the major component in SD-EO and MAHD-EO (40.84 and 40.04 %, respectively); while in HD-EO it only represented 15.36 %. The SD-EO showed a strong antiviral activity against HCoV-229E with IC50 of 10.93 µg/mL, whereas, MAHD-EO and HD-EO showed a moderate activity with IC50 values of 119.9 and 148.2 µg/mL, respectively. The molecular docking of EO major components: phytol, octadecyl acetate and tricosane showed a strong binding to coronavirus 3-CL (pro). Moreover, the three EOs (50 µg/mL) decreased the levels of NO, IL-6 and TNF-α and suppressed IL-6 and TNF-α gene expression in LPS-induced inflammation model in RAW264.7 macrophage cell lines.


Assuntos
Cestrum , Coronavirus Humano 229E , Óleos Voláteis , Cestrum/química , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Interleucina-6 , Lipopolissacarídeos/farmacologia , Simulação de Acoplamento Molecular , Óleos Voláteis/química , Extratos Vegetais/química , Fator de Necrose Tumoral alfa , Antivirais/química , Antivirais/farmacologia
8.
Molecules ; 28(10)2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37241926

RESUMO

Gynura procumbens (Lour.) Merr. (Family: Asteraceae) is a tropical Asian medicinal plant found in Thailand, China, Malaysia, Indonesia, and Vietnam. It has long been utilized to treat a variety of health concerns in numerous countries around the world, such as renal discomfort, constipation, diabetes mellitus, rheumatism, and hypertension. The chemical investigation resulted in the isolation and characterization of six compounds from the methanol (MeOH) extract of the leaves of Gynura procumbens, which were identified as phytol (1), lupeol (2), stigmasterol (3), friedelanol acetate (4), ß-amyrin (5), and a mixture of stigmasterol and ß-sitosterol (6). In-depth investigations of the high-resolution 1H NMR and 13C NMR spectroscopic data from the isolated compounds, along with comparisons to previously published data, were used to clarify their structures. Among these, the occurrence of Compounds 1 and 4 in this plant are reported for the first time. The crude methanolic extract (CME) and its different partitionates, i.e., petroleum ether (PESF), chloroform (CSF), ethyl acetate (EASF), and aqueous (AQSF) soluble fractions, were subjected to antioxidant, cytotoxic, thrombolytic, and anti-diabetic activities. In a DPPH free radical scavenging assay, EASF showed the maximum activity, with an IC50 value of 10.78 µg/mL. On the other hand, CSF displayed the highest cytotoxic effect with an LC50 value of 1.94 µg/mL compared to 0.464 µg/mL for vincristine sulphate. In a thrombolytic assay, the crude methanolic extract exhibited the highest activity (63.77%) compared to standard streptokinase (70.78%). During the assay for anti-diabetic activity, the PESF showed 70.37% of glucose-lowering activity, where standard glibenclamide showed 63.24% of glucose-reducing activity.


Assuntos
Antineoplásicos , Asteraceae , Extratos Vegetais/química , Bangladesh , Estigmasterol , Compostos Fitoquímicos/farmacologia , Asteraceae/química , Antioxidantes/farmacologia , Antioxidantes/química , Descoberta de Drogas , Glucose
9.
J Biol Chem ; 296: 100802, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34022219

RESUMO

Understanding the pathways involved in chlorophyll breakdown provides a molecular map to the color changes observed in plant life on a global scale each fall. Surprisingly, little is known about the fate of phytol, chlorophyll's 20-carbon branched-chain tail, during this process. A recent study from Gutbrod et al. provides evidence using physiological, genetic, and exquisitely sensitive analytical approaches that phytenal is an intermediate in plant phytol catabolism. These insights and techniques open the door to further investigation of this complicated metabolic system, with implications for plant health and agriculture.


Assuntos
Clorofila/metabolismo , Fitol/metabolismo , Arabidopsis/metabolismo , Folhas de Planta/metabolismo
10.
J Biol Chem ; 296: 100530, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33713704

RESUMO

Phytol is the isoprenoid alcohol bound in ester linkage to chlorophyll, the most abundant photosynthetic pigment in plants. During leaf senescence, large amounts of phytol are released by chlorophyll degradation. However, the pathway of phytol catabolism in plants is unknown. We hypothesized that phytol degradation in plants might involve its oxidation into the long-chain aldehyde phytenal. Using GC-MS for aldehyde quantification after derivatization with methylhydroxylamine, phytenal was identified in leaves, whereas other long-chain aldehydes (phytanal and pristanal) were barely detectable. We found that phytenal accumulates during chlorotic stresses, for example, salt stress, dark-induced senescence, and nitrogen deprivation. The increase in the phytenal content is mediated at least in part independently of enzyme activities, and it is independent of light. Characterization of phytenal accumulation in the pao1 mutant affected in chlorophyll degradation revealed that phytenal is an authentic phytol metabolite derived from chlorophyll breakdown. The increase in phytenal was even stronger in mutants affected in the production of other phytol metabolites including vte5-2 (tocopherol deficient) and pes1 pes2 (fatty acid phytyl ester deficient). Therefore, phytenal accumulation is controlled by competing, alternative pathways of phosphorylation (leading to tocopherol production) or esterification (fatty acid phytyl ester production). As a consequence, the content of phytenal is maintained at low levels, presumably to minimize its toxic effects caused by its highly reactive aldehyde group that can form covalent bonds with and inactivate the amino groups of proteins.


Assuntos
Arabidopsis/metabolismo , Clorofila/metabolismo , Fitol/metabolismo , Folhas de Planta/metabolismo , Tocoferóis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Hidrólise , Fosforilação , Fotossíntese , Folhas de Planta/crescimento & desenvolvimento
11.
Nutr Neurosci ; 25(3): 485-501, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32406811

RESUMO

OBJECTIVE: Alzheimer's disease (AD) is an acquired neurological disorder of cognitive and behavioral impairments, with a long and progressive route. Currently, efforts are being made to develop potent drugs that target multiple pathological mechanisms that drive the successful treatment of AD in human beings. The development of nano-drug delivery systems has recently emerged as an effective strategy to treat AD. METHODS: In the present study, the protective effect of Phytol and Phytol loaded Poly Lactic-co-Glycolic Acid nanoparticles (Phytol-PLGANPs) were evaluated in Wistar rat scopolamine model of AD. RESULTS AND DISCUSSION: The consumption of Phytol and Phytol-PLGANPs significantly ameliorated the cognitive deficits caused by scopolamine on spatial and short term memory. Phytol and Phytol-PLGANPs significantly enhanced the cholinergic effect by inhibiting both acetylcholinesterase and butyrylcholinesterase (AChE & BuChE), ß-secretase 1 (BACE1) activity, attenuating macromolecular damage, reducing reactive oxygen species (ROS) and reactive nitrogen species (RNS) level by activating antioxidative defense system (Superoxide dismutase and catalase) and restoring glutathione metabolizing enzyme systems (Glutathione S-transferase) and also regulating the apoptotic mediated cell death. Moreover, in vivo toxicity study suggests that Phytol and Phytol-PLGANPs did not cause any adverse pathological alteration in rats treated with a higher concentration of Phytol-PLGANPs (200 mg/kg). Pharmacokinetic study revealed that Phytol-PLGANPs enhanced the biodistribution and sustained the release profile of phytol in the brain and plasma. CONCLUSION: Overall, the outcome of the study suggests that Phytol and Phytol-PLGANPs act as a potent candidate with better anti-amnesic effects and multi-faceted neuroprotective potential against scopolamine-induced memory dysfunction in Wistar rats.


Assuntos
Disfunção Cognitiva , Nanopartículas , Fármacos Neuroprotetores , Acetilcolinesterase/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Apoptose , Ácido Aspártico Endopeptidases/metabolismo , Ácido Aspártico Endopeptidases/farmacologia , Butirilcolinesterase/metabolismo , Butirilcolinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Inibidores da Colinesterase/toxicidade , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo , Fitol/farmacologia , Ratos , Ratos Wistar , Escopolamina , Distribuição Tecidual
12.
Molecules ; 27(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36364126

RESUMO

In this study, a novel galloyl phytol antioxidant was developed by incorporating the branched phytol chain with gallic acid through mild Steglich esterification. The evaluation of the radical scavenging activity, lipid oxidation in a liposomal model, and glycerol trioleate revealed its superior antioxidant activities in both dispersed and bulk oils. Then, the antioxidant capacity enhancement of galloyl phytol was further explored using thermal gravimetry/differential thermal analysis (TG/DTA), transmission electron microscopy (TEM), and molecular modeling. The EC50 values of GP, GPa, and GE were 0.256, 0.262, and 0.263 mM, respectively, which exhibited comparable DPPH scavenging activities. These investigations unveiled that the branched aliphatic chain enforced the coiled molecular conformation and the unsaturated double bond in the phytol portion further fixed the coiled conformation, which contributed to a diminished aggregation tendency and enhanced antioxidant activities in dispersed and bulk oils. The remarkable antioxidant performance of galloyl phytol suggested intriguing and non-toxic natural antioxidant applications in the food industry, such as effectively inhibiting the oxidation of oil and improvement of the quality and shelf life of the oil, which would contribute to the use of tea resources and extending the tea industry chain.


Assuntos
Antioxidantes , Fitol , Fitol/farmacologia , Antioxidantes/química , Esterificação , Óleos de Plantas/química , Chá
13.
Molecules ; 27(15)2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35956941

RESUMO

The present study aimed to isolate volatile organic compounds (VOCs) from fresh (FrHSc) and air-dried (DrHSc) Halopteris scoparia (from the Adriatic Sea) by headspace solid-phase microextraction (HS-SPME) and hydrodistillation (HD) and to analyse them by gas chromatography and mass spectrometry (GC-MS). The impact of the season of growth (May-September) and air-drying on VOC composition was studied for the first time, and the obtained data were elaborated by principal component analysis (PCA). The most abundant headspace compounds were benzaldehyde, pentadecane (a chemical marker of brown macroalgae), and pentadec-1-ene. Benzaldehyde abundance decreased after air-drying while an increment of benzyl alcohol after drying was noticed. The percentage of pentadecane and heptadecane increased after drying, while pentadec-1-ene abundance decreased. Octan-1-ol decreased from May to September. In HD-FrHSc, terpenes were the most abundant in June, July, and August, while, in May and September, unsaturated aliphatic compounds were dominant. In HD-DrHSc terpenes, unsaturated and saturated aliphatic compounds dominated. (E)-Phytol was the most abundant compound in HD-FrHSc through all months except September. Its abundance increased from May to August. Two more diterpene alcohols (isopachydictyol A and cembra-4,7,11,15-tetraen-3-ol) and sesquiterpene alcohol gleenol were also detected in high abundance. Among aliphatic compounds, the dominant was pentadec-1-ene with its peak in September, while pentadecane was present with lower abundance. PCA (based on the dominant compound analyses) showed distinct separation of the fresh and dried samples. No correlation was found between compound abundance and temperature change. The results indicate great seasonal variability of isolated VOCs, as well among fresh and dried samples, which is important for further chemical biodiversity studies.


Assuntos
Phaeophyceae , Scoparia , Alga Marinha , Compostos Orgânicos Voláteis , Álcoois/análise , Benzaldeídos , Phaeophyceae/química , Microextração em Fase Sólida/métodos , Terpenos , Compostos Orgânicos Voláteis/análise
14.
Molecules ; 27(20)2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36296714

RESUMO

Annona macroprophyllata Donn (A. macroprophyllata) is used in traditional Mexican medicine for the treatment of cancer, diabetes, inflammation, and pain. In this work, we evaluated the antitumor activity of three acyclic terpenoids obtained from A. macroprophyllata to assess their potential as antilymphoma agents. We identified the terpenoids farnesyl acetate (FA), phytol (PT) and geranylgeraniol (Gg) using gas chromatography-mass spectroscopy (GC-MS) and spectroscopic (1H, and 13C NMR) methods applied to petroleum ether extract of leaves from A. macroprophyllata (PEAm). We investigated antitumor potential in Balb/c mice inoculated with U-937 cells by assessing brine shrimp lethality (BSL), and cytotoxic activity in these cells. In addition, to assess the potential toxicity of PEAm, FA, PT and Gg in humans, we tested their acute oral toxicity in mice. Our results showed that the three terpenoids exhibited considerable antilymphoma and cytotoxic activity. In terms of lethality, we determined a median lethal dose (LD50) for thirteen isolated products of PEAm. Gg, PT and AF all exhibited a higher lethality with values of 1.41 ± 0.42, 3.03 ± 0.33 and 5.82 ± 0.58 µg mL-1, respectively. To assess cytotoxic activity against U-937 cells, we calculated the mean cytotoxic concentration (CC50) and found that FA and PT were closer in respect to the control drug methotrexate (MTX, 0.243 ± 0.007 µM). In terms of antilymphoma activity, we found that FA, PT and Gg considerably inhibited lymph node growth, with median effective doses (ED50) of 5.89 ± 0.39, 6.71 ± 0.31 and 7.22 ± 0.51 mg kg-1 in females and 5.09 ± 0.66, 5.83 ± 0.50 and 6.98 ± 0.57mg kg -1 in males, respectively. Regarding acute oral toxicity, we classified all three terpenoids as category IV, indicating a high safety margin for human administration. Finally, in a molecular docking study of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, we found binding of terpenoids to some amino acids of the catalytic site, suggesting an effect upon activity with a resulting decrease in the synthesis of intermediates involved in the prenylation of proteins involved in cancer progression. Our findings suggest that the acyclic terpenoids FA, PT, and Gg may serve as scaffolds for the development of new treatments for non-Hodgkin's lymphoma.


Assuntos
Annona , Antineoplásicos , Masculino , Feminino , Camundongos , Humanos , Animais , Annona/química , Terpenos/farmacologia , Simulação de Acoplamento Molecular , Metotrexato , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antineoplásicos/farmacologia , Fitol , Aminoácidos
15.
Plant Foods Hum Nutr ; 77(2): 265-270, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35618894

RESUMO

α-tocopherol is found in high concentrations in avocado fruit mesocarp, however, its accumulation and genetic control during maturation and ripening has not been elucidated. Based in the relevance of VTE1 and VTE5 genes in tocopherol biosynthesis and aiming to determine the association between tocopherol accumulation and expression of tocopherol biosynthetic genes, gene expression of VTE1 and VTE5 were evaluated through the time during three developmental stages: before harvest at 100, 160 and 220 days after flowering (DAF) and after harvest (220 DAF + 5) in two contrasting avocado genotypes (San Miguel and AVO40). San Miguel reached the highest levels at 220 DAF, whereas AVO40 increased α-tocopherol only after ripening (220 DAF + 5). A genome-wide search for VTE1 and VTE5 allowed to identify one and three genes, respectively. Both genotypes showed contrasting patterns of gene expression. Interestingly, AVO40 showed a highly positive correlation between α-tocopherol levels and gene expression of VTE1 and all VTE5 variants. On the other hand, San Miguel showed only a positive correlation between α-tocopherol level and VTE1gene expression.


Assuntos
Persea , Tocoferóis , Frutas/genética , Regulação da Expressão Gênica de Plantas , Genótipo , Persea/genética , Vitamina E/metabolismo , alfa-Tocoferol/metabolismo
16.
J Sep Sci ; 44(19): 3654-3664, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34324250

RESUMO

Fast, cheap, and simple separation of lipids and hydrocarbons can currently be achieved using thin-layer chromatography. Here, we describe an alternative planar chromatographic method using polyvinylidene difluoride membranes as the stationary phase. The procedure has the same advantages of thin-layer chromatography over other expensive and time-consuming techniques, such as high-performance liquid chromatography or gas chromatography. Polyvinylidene difluoride membranes, however, also provide an immediate support for analyte development via immunodetection, are easy to manipulate, and potentially increase the performance of other detection methods. We show that polyvinylidene difluoride membranes are compatible with a variety of solvents that can migrate by capillarity and redistribute analytes between the membrane and the solvent according to their relative affinities, providing a chromatographic separation. We directly test the developed membranes by immunoblotting using anti-squalene antibodies that cross-react with acyclic isoprenoids. Separations of crude oils and plant extracts under different solvent conditions show the potential to resolve hydrocarbon group types and also to provide characteristic fingerprints of plant pigments and squalene degradation products. Polyvinylidene difluoride membranes prove useful as a stationary phase for planar chromatography and for the subsequent immunodetection of the separated compounds, providing a new and simple chromatographic technique to analyze lipids and hydrocarbons.

17.
Inhal Toxicol ; 33(1): 33-40, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33441006

RESUMO

Introduction: The use of vaping pens for inhalation of cannabinoid derived products is rising and has become a popular alternative to smoking combustible products. For efficient product delivery, additives are sometimes added and vaping pens often may include compounds like Phytol or Propylene Glycol as thinning agents. This study aimed at comparing Phytol and Propylene Glycol with respect to potential toxicity and safe use in vaping products.Methods: Male and female Sprague Dawley rats were exposed to 5 mg/L of Phytol or Propylene Glycol for up to 6 hours over up to 14 days and monitored for clinical signs and changes in body weight. Gross necropsy and histopathology of respiratory tissue was performed to assess potential adverse effects.Results: Phytol exposed animals expressed severe clinical signs, body weight loss and mortality after one or two exposure days, leading to termination of all dose groups for this compound. Lung weights were increased and respiratory tissue was severely affected, demonstrating dose-responsive tissue degeneration, necrosis, edema, hemorrhage and inflammation. Propylene Glycol exposed animals did not show any adverse reactions after 14 days of high dose exposure.Conclusions: For Phytol, a low observed adverse effect level (LOAEL) was determined at ≤109.0/10.9 mg/kg/day presented/deposited dose and therefore its use as excipient in vaping product is not recommend; a safe exposure range was not established for Phytol. Propylene Glycol, in contrast, is considered safe with a no observed adverse effect level (NOAEL) at 1151.7/115.2 mg/kg/day presented/deposited dose in rats.


Assuntos
Lesão Pulmonar/induzido quimicamente , Fitol/toxicidade , Propilenoglicol/toxicidade , Animais , Feminino , Exposição por Inalação , Masculino , Ratos , Ratos Sprague-Dawley
18.
Exp Parasitol ; 224: 108097, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33736972

RESUMO

The quest for the development of a novel antimalarial drug informed the decision to subject phytol to in vivo trials following a demonstration of therapeutic potential against chloroquine sensitive strain of Plasmodium falciparum under in vitro condition. On this basis, the in vivo anti-Plasmodium berghei activity of phytol including the ameliorative effects of the compound on P. berghei-associated anaemia and organ damage were investigated. Mice were infected with chloroquine-sensitive strain of P. berghei and were treated with phytol at a dose of 10 and 20 mg/kg body weight (BW) for four days. The levels of parasitemia, packed cell volume and redox sensitive biomarkers of liver, brain and spleen tissues were determined. Our result revealed that phytol significantly (p < 0.05) suppressed the multiplication of P. berghei in a dose-dependent manner. Additionally, the phytol significantly (p < 0.05) ameliorated the P. berghei-induced anaemia and brain damage. Data from the present study demonstrated that phytol has suppressive effect on P. berghei and could ameliorate some P. berghei-induced pathological changes.


Assuntos
Malária/tratamento farmacológico , Fitol/uso terapêutico , Plasmodium berghei/efeitos dos fármacos , Análise de Variância , Anemia/tratamento farmacológico , Anemia/parasitologia , Animais , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Encéfalo/parasitologia , Encéfalo/patologia , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Hematócrito , Fígado/parasitologia , Fígado/patologia , Malária/sangue , Malária/parasitologia , Malária/patologia , Masculino , Camundongos , Oxirredução/efeitos dos fármacos , Parasitemia/tratamento farmacológico , Fitol/farmacologia , Distribuição Aleatória , Baço/parasitologia , Baço/patologia
19.
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
20.
Chem Biodivers ; 18(8): e2100241, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34081830

RESUMO

Artemisia fragrans is commonly used as a folk medicine as antispasmodic, anti-pyretic, anti-inflammatory, and abortifacient agents. The villagers use its pungent odor to repel rodents, mites, and pests, as well as its essential oil and smoke after burning to treat lung infections after uprooting the plant. Herein, we extracted the essential oils (EOs) of different parts of the plant and analyzed their chemical compositions and antibacterial activities. The chemical analysis led to the identification of 73, 59, and 57 compounds in the EOs of the stem, leaf, and flower, respectively. All of the EOs exhibited antibacterial activities against both G+ and G- bacteria. The EOs of the leaf and flower were more effective against tested bacteria, except B. anthracis and P. aeruginosa, compared to that of the stem. The binary combination of the EOs (stem and flower) or (stem and leaf) showed a synergistic effect. Statistical analysis indicated EOs of leaf and flower are more potent than that of the stem. These findings suggest the application of leaf and flower of the plant, which not only can prevent its uprooting but also ensure better therapeutic function.


Assuntos
Anti-Infecciosos/química , Artemisia/química , Óleos Voláteis/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Artemisia/metabolismo , Flores/química , Flores/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Medicina Tradicional , Testes de Sensibilidade Microbiana , Óleos Voláteis/farmacologia , Folhas de Planta/química , Folhas de Planta/metabolismo , Caules de Planta/química , Caules de Planta/metabolismo , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/farmacologia
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