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Biomedicine & Pharmacotherapy =... Jan 2022Oxidative stress is considered the main cause of cellular damage in a number of neurodegenerative disorders. One suitable ways to prevent cell damage is the use of the...
Oxidative stress is considered the main cause of cellular damage in a number of neurodegenerative disorders. One suitable ways to prevent cell damage is the use of the exogenous antioxidant capacity of natural products, such as microalgae. In the present study, four microalgae extracts, isolated from the Persian Gulf, were screened to analyze their potential antioxidant activity and free radical scavenging using ABTS, DPPH, and FRAP methods. The methanolic extracts (D1M) of green microalgae derived from Chlorella sp. exhibited potent free radical scavenging activity. In order to characterize microalgae species, microscopic observations and analysis of the expression of 18S rRNA were performed. The antioxidant and neuroprotective effects of D1M on HO-induced toxicity in PC12 cells were investigated. The results demonstrated that D1M significantly decreased the release of nitric oxide (NO), formation of intracellular reactive oxygen species (ROS), and the level of malondialdehyde (MDA), whereas it enhanced the content of glutathione (GSH), and activity of heme oxygenase 1 (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1), and catalase (CAT) in PC12 cells exposed to HO. The pretreatment of D1M improved cell viability as measured by the MTT assay and invert microscopy, reduced cell apoptosis as examined by flow cytometry analysis, increased mitochondrial membrane potential (MMP), and diminished caspase-3 activity. The GC/MS analysis revealed that D1M ingredients have powerful antioxidant and anti-inflammatory compounds, such as butylated hydroxytoluene (BHT), 2,4-di-tert-butyl-phenol (2,4-DTBP), and phytol. These results suggested that Chlorella sp. extracts have strong potential to be applied as neuroprotective agents, for the treatment of neurodegenerative disorders.
Topics: Animals; Antioxidants; Apoptosis; Butylated Hydroxytoluene; Cell Survival; Chlorella; Free Radical Scavengers; Hydrogen Peroxide; Membrane Potential, Mitochondrial; Neurodegenerative Diseases; Neuroprotective Agents; Oxidative Stress; PC12 Cells; Phenols; Phytol; Rats; Reactive Oxygen Species
PubMed: 34775236
DOI: 10.1016/j.biopha.2021.112415 -
Colloids and Surfaces. B, Biointerfaces Mar 2021Phytol, a pharmacologically active compound present in Corchorus olitorius leaf exhibit a range of activity including anti-inflammatory, antioxidant, anticancer,...
Phytol, a pharmacologically active compound present in Corchorus olitorius leaf exhibit a range of activity including anti-inflammatory, antioxidant, anticancer, hepatoprotective etc. However, phytol is poorly soluble and absorbed through the intestine wall, therefore the aim of this study is to develop liposomal drug delivery of Corchorus olitorius leaf extract with an average particle size below 150 nm and drug loading efficiency of ≥ 85 %. The impact of different process parameters and material attributes were studied on the average particle size and polydispersity of liposomal batches using design of experiment (DoE). Corchorus olitorius leaf extraction was performed using maceration method and characterised using GC-MS. Liposomal batches of Corchorus olitorius leaf extract were characterized using Malvern zetasizer, transmission electron microscopy (TEM) and UV spectroscopy. The in-vivo anti-inflammatory study of the liposomal preparation of phytol was evaluated using a rat model and in-vitro cancer cell line study was performed on AML and Leukamia cell lines. GC-MS study data showed that phytol is present in C. olitorius leaf extract. Process parameters and material attributes perspective processing temperature, buffer pH and drug: lipid ratio is found as major parameters affecting the average particle size and PDI value of liposomes. Liposomes were prepared in the range of 80-250 nm and optimized batches of liposomes showed drug entrapment efficiency of 60-88 %. In-vivo anti-inflammatory study showed significant activity for C. olitorius leaf extract against carrageenan induced paw edema, which is significantly increased while delivered through liposomes. In-vitro cancer cell line study data suggests that liposomal delivery of phytol was more active at lower concentration compared to pure phytol, for specific cell lines.
Topics: Animals; Anti-Inflammatory Agents; Corchorus; Liposomes; Phytol; Plant Extracts; Rats
PubMed: 33360927
DOI: 10.1016/j.colsurfb.2020.111543 -
Food and Chemical Toxicology : An... Mar 2024
Topics: Phytol; Odorants
PubMed: 38040233
DOI: 10.1016/j.fct.2023.114270 -
Plant Physiology Sep 2014Phytyl diphosphate (PDP) is the prenyl precursor for tocopherol biosynthesis. Based on recent genetic evidence, PDP is supplied to the tocopherol biosynthetic pathway...
Phytyl diphosphate (PDP) is the prenyl precursor for tocopherol biosynthesis. Based on recent genetic evidence, PDP is supplied to the tocopherol biosynthetic pathway primarily by chlorophyll degradation and sequential phytol phosphorylation. Three enzymes of Arabidopsis (Arabidopsis thaliana) are known to be capable of removing the phytol chain from chlorophyll in vitro: chlorophyllase1 (CLH1), CLH2, and pheophytin pheophorbide hydrolase (PPH), which specifically hydrolyzes pheophytin. While PPH, but not chlorophyllases, is required for in vivo chlorophyll breakdown during Arabidopsis leaf senescence, little is known about the involvement of these phytol-releasing enzymes in tocopherol biosynthesis. To explore the origin of PDP for tocopherol synthesis, seed tocopherol concentrations were determined in Arabidopsis lines engineered for seed-specific overexpression of PPH and in single and multiple mutants in the three genes encoding known dephytylating enzymes. Except for modestly increasing tocopherol content observed in the PPH overexpressor, none of the remaining lines exhibited significantly reduced tocopherol concentrations, suggesting that the known chlorophyll-derived phytol-releasing enzymes do not play major roles in tocopherol biosynthesis. Tocopherol content of seeds from double mutants in NONYELLOWING1 (NYE1) and NYE2, regulators of chlorophyll degradation, had modest reduction compared with wild-type seeds, although mature seeds of the double mutant retained significantly higher chlorophyll levels. These findings suggest that NYEs may play limited roles in regulating an unknown tocopherol biosynthesis-related phytol hydrolase. Meanwhile, seeds of wild-type over-expressing NYE1 had lower tocopherol levels, suggesting that phytol derived from NYE1-dependent chlorophyll degradation probably doesn't enter tocopherol biosynthesis. Potential routes of chlorophyll degradation are discussed in relation to tocopherol biosynthesis.
Topics: Arabidopsis; Carboxylic Ester Hydrolases; Chlorophyll; Hydrolases; Mutagenesis, Insertional; Phytol; Seeds; Tocopherols
PubMed: 25059706
DOI: 10.1104/pp.114.243709 -
Cellular Immunology 2011In a previous report, we observed that the phytol-derived immunostimulant, PHIS-01 (phytanol), is a nontoxic oil-in-water adjuvant which is superior to most commercial...
In a previous report, we observed that the phytol-derived immunostimulant, PHIS-01 (phytanol), is a nontoxic oil-in-water adjuvant which is superior to most commercial adjuvants. In contrast, the parent diterpene alcohol phytol, though highly effective as an adjuvant, is relatively toxic. To assess the importance of the polar functional group in PHIS-01, we prepared two new compounds PHIS-02 (phytanyl amine) and PHIS-03 (phytanyl mannose). All three phytol derivatives proved to be excellent adjuvants, but differed in solubility and mode of action. To delineate their molecular signatures in the local microenvironment, we performed inflammasome and cytokine microarray analyses with the peritoneal fluid of mice treated with alum or the phytol compounds above, in the presence or absence of soluble protein antigens. We report here that the phytol derivatives had a significant time-dependent impact on the host chemokine-cytokine microenvironment and subsequently on specific humoral responses. Moreover, the inclusion of protein immunogens induced further changes in host microenvironments, including rapid (<2h) expression of cytokines and chemotactic factors (IL-6, MCP-1, KC, MIP-1, and LIX), implying mobilization and activation of neutrophils, and monocytes. PHIS-01 proved to be the most effective in this regard. Inflammatory cytokine cascades were dominant even after 24h possibly to facilitate involvement of the acquired immune system with the release of B-lymphocyte chemo-attractant BLC, T-cell activation-3 chemokines TCA, IL-4, IL-12, and TIMP-1. We also noted enhanced expression of NLRP genes including NLRP3 with both alum and phytol derivatives (particularly PHIS-01).
Topics: Adjuvants, Immunologic; Animals; Ascitic Fluid; Carrier Proteins; Cellular Microenvironment; Chemokines; Cytokines; Female; Immunity, Innate; Inflammasomes; Mice; Mice, Inbred BALB C; NLR Family, Pyrin Domain-Containing 3 Protein; Phytol; Protein Array Analysis; Reverse Transcriptase Polymerase Chain Reaction; Transcriptional Activation
PubMed: 21813116
DOI: 10.1016/j.cellimm.2011.07.001 -
Chemosphere Jun 2017Phytol (PYT) is a diterpenoid having important biological activity. However, it is a water non-soluble compound. This study aims to prepare PYT nanoemulsion (PNE) and...
Phytol (PYT) is a diterpenoid having important biological activity. However, it is a water non-soluble compound. This study aims to prepare PYT nanoemulsion (PNE) and evaluation of toxic, cytotoxic and genotoxic activities of PYT and PNE. For this, the PNE was prepared by the phase inversion method. The cytotoxicity test was performed in Artemia salina, while toxicity, cytotoxicity and genotoxicity in Allium cepa at concentrations of 2, 4, 8 and 16 mM. Potassium dichromate and copper sulfate were used as positive controls for the tests of A. salina and A. cepa, respectively. In addition, an adaptation response was detected in A. cepa by using the comet assay. The results suggest that both PYT and PNE exhibited toxic and cytotoxic effects at 4-16 mM in either test system, while genotoxicity at 2-16 mM in A. cepa. PNE exhibited more toxic, cytotoxic and genotoxic effects at 8 and 16 mM than the PYT. However, both PYT and PNE at 2 and 4 mM decreased the index and frequency of damage in A. cepa after 48 and 72 h, suggesting a possible adaptation response or DNA damage preventing capacity. Nanoemulsified PYT (PNE) may readily cross the biological membranes with an increase in bioavailability and produce more toxic, cytotoxic and genotoxic effects in the used test systems.
Topics: Animals; Artemia; Comet Assay; DNA Damage; Emulsions; Nanoparticles; Onions; Phytol
PubMed: 28284120
DOI: 10.1016/j.chemosphere.2017.02.145 -
Trends in Molecular Medicine Oct 2022Phylloquinone (vitamin K1) and menaquinones (vitamin K2 family) are essential for post-translational γ-carboxylation of a small number of proteins, including clotting... (Review)
Review
Phylloquinone (vitamin K1) and menaquinones (vitamin K2 family) are essential for post-translational γ-carboxylation of a small number of proteins, including clotting factors. These modified proteins have now been implicated in diverse physiological and pathological processes including cancer. Vitamin K intake has been inversely associated with cancer incidence and mortality in observational studies. Newly discovered functions of vitamin K in cancer cells include activation of the steroid and xenobiotic receptor (SXR) and regulation of oxidative stress, apoptosis, and autophagy. We provide an update of vitamin K biology, non-canonical mechanisms of vitamin K actions, the potential functions of vitamin K-dependent proteins in cancer, and observational trials on vitamin K intake and cancer.
Topics: Biology; Humans; Neoplasms; Pregnane X Receptor; Proteins; Vitamin K; Vitamin K 1; Vitamin K 2
PubMed: 36028390
DOI: 10.1016/j.molmed.2022.07.002 -
Frontiers in Cellular and Infection... 2017Quorum Sensing (QS) mechanism, a bacterial density-dependent gene expression system, governs the pathogenesis through the production of virulence factors and biofilm...
Quorum Sensing (QS) mechanism, a bacterial density-dependent gene expression system, governs the pathogenesis through the production of virulence factors and biofilm formation. The present study demonstrates the anti-quorum sensing (anti-QS), antibiofilm potential and protective effect of phytol, a diterpene alcohol broadly utilized as food additive and in therapeutics fields. treatment of phytol (5 and 10 μg/ml) showed decreasing level of biofilm formation, lipase and hemolysin production in compared to their respective controls. More, microscopic analyses confirmed the antibiofilm potential of phytol. The biofilm related phenomenons such as swarming motility and exopolysccharide productions were also inhibited by phytol. Furthermore, the real-time analysis elucidated the molecular mechanism of phytol which showed downregulation of , and gene expressions. On the other hand, the rescue effect of phytol was assessed against associated acute pyelonephritis in Wistar rat. Compared to the infected and vehicle controls, the phytol treated groups (100 and 200 mg/kg) showed decreased level of bacterial counts in kidney, bladder tissues and urine samples on the 5th post infection day. As well, the phytol treatment showed reduced level of virulence enzymes such as lipase and protease productions compared to the infected and vehicle controls. Further, the infected and vehicle controls showed increasing level of inflammatory markers such as malondialdehyde (MDA), nitric oxide (NO) and myeloperoxidase (MPO) productions. In contrast, the phytol treatment showed decreasing level of inflammatory markers. In histopathology, the uninfected animal showed normal kidney and bladder structure, wherein, the infected animals showed extensive infiltration of neutrophils in kidney and bladder tissues. In contrast, the phytol treatment showed normal kidney and bladder tissues. Additionally, the toxic effect of phytol (200 mg/kg) was assessed by single dose toxicity analysis. No changes were observed in hematological, biochemical profiles and histopathological analysis of vital organs in phytol treated animals compared to the untreated controls. Hence, this study suggested the potential use of phytol for its anti-QS, antibiofilm and anti-inflammatory properties against infections and their associated inflammation reactions.
Topics: Animals; Bacterial Proteins; Biofilms; Disease Models, Animal; Female; Fimbriae Proteins; Gene Expression; Genes, Bacterial; Hemolysin Proteins; Kidney; Lipase; Malondialdehyde; Neutrophils; Nitric Oxide; Peroxidase; Phytol; Pyelonephritis; Quorum Sensing; Rats; Rats, Wistar; Serratia marcescens; Urinary Bladder; Urine; Virulence; Virulence Factors
PubMed: 29259923
DOI: 10.3389/fcimb.2017.00498 -
Natural Product Research 2015Anti-quorum sensing activity of the diterpene phytol was evaluated in vitro for the first time. This compound (at three sub-MIC concentrations - 0.5, 0.25 and 0.125 MIC,...
Anti-quorum sensing activity of the diterpene phytol was evaluated in vitro for the first time. This compound (at three sub-MIC concentrations - 0.5, 0.25 and 0.125 MIC, respectively) reduced the formation of Pseudomonas aeruginosa PAO1 biofilm in the range of 74.00-84.33% exhibiting higher activity than the both positive controls used, streptomycin and ampicillin. Phytol (0.5 MIC) also effectively reduced P. aeruginosa twitching and flagella motility. Indeed, the bacteria treated were incapable of producing a twitching zone and had almost round, smooth and regular colony edges. Finally, the tested compound (0.5 MIC) exhibited good P. aeruginosa pyocyanin inhibitory activity (51.94%) practically to the same extent as streptomycin (52.09%). According to the experimental data obtained, this phytol property may inspire design of medical foods targeting P. aeruginosa quorum sensing activity.
Topics: Anti-Bacterial Agents; Biofilms; Molecular Structure; Phytol; Pseudomonas aeruginosa; Quorum Sensing
PubMed: 25103916
DOI: 10.1080/14786419.2014.945088 -
Biochimica Et Biophysica Acta Aug 1986The enzymatic conversion of phytol to phytanic acid was investigated in rat liver postnuclear and other subcellular fractions using [1-3H]phytol as the substrate. The...
The enzymatic conversion of phytol to phytanic acid was investigated in rat liver postnuclear and other subcellular fractions using [1-3H]phytol as the substrate. The assay method involved incubation of the substrate with appropriate cofactors and the enzyme source, followed by subjecting the mixture to Folch partition and measuring the radioactivity in the upper layer. The phytol-phytanate conversion activity was present in mitochondrial and microsomal fractions. Cytosol had no activity. In mitochondrial fraction, investigation of cofactor requirements indicated that only NAD was required for activity. Other pyridine nucleotides supported the activity to a lesser extent when compared with NAD. FAD at 1 mM concentration did not support the activity. Bovine serum albumin (0.4 mg/ml) stimulated the activity. The reaction did not require molecular oxygen. From substrate kinetic studies, an apparent Km of 14.3 and 11.1 microM was calculated for phytol in mitochondrial and microsomal fractions, respectively. The amount of tritiated water produced from incubation increased linearly up to 7-8 min. The activity was linear with the amount of mitochondrial and microsomal protein up to 200 and 40 micrograms, respectively. Among the various rat tissue homogenates tested, liver had the highest activity. Spleen and kidney had 8-9% of the activity of liver. Brain possessed negligible activity. Both ethanol and pyrazole had no inhibitory effect on phytol-phytanate conversion. This observation and the absence of activity in cytosol suggests that alcohol dehydrogenase may not be involved in phytol-phytanate conversion.
Topics: Animals; Diterpenes; Eicosanoic Acids; Isotope Labeling; Kinetics; Liver; Male; Microsomes, Liver; Mitochondria, Liver; NAD; Oxygen; Phytanic Acid; Phytol; Rats; Rats, Inbred Strains; Serum Albumin, Bovine; Tissue Distribution; Tritium
PubMed: 3730426
DOI: 10.1016/0304-4165(86)90134-0