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Progress in Lipid Research Apr 2019Phytol, the prenyl side chain of chlorophyll, is derived from geranylgeraniol by reduction of three double bonds. Recent results demonstrated that the conversion of... (Review)
Review
Phytol, the prenyl side chain of chlorophyll, is derived from geranylgeraniol by reduction of three double bonds. Recent results demonstrated that the conversion of geranylgeraniol to phytol is linked to chlorophyll synthesis, which is catalyzed by protein complexes associated with the thylakoid membranes. One of these complexes contains light harvesting chlorophyll binding like proteins (LIL3), enzymes of chlorophyll synthesis (protoporphyrinogen oxidoreductase, POR; chlorophyll synthase, CHLG) and geranylgeranyl reductase (GGR). Phytol is not only employed for the synthesis of chlorophyll, but also for tocopherol (vitamin E), phylloquinol (vitamin K) and fatty acid phytyl ester production. Previously, it was believed that phytol is derived from reduction of geranylgeranyl-diphosphate originating from the 4-methylerythritol-5-phosphate (MEP) pathway. The identification and characterization of two kinases, VTE5 and VTE6, involved in phytol and phytyl-phosphate phosphorylation, respectively, indicated that most phytol employed for tocopherol synthesis is derived from reduction of geranylgeranylated chlorophyll to (phytol-) chlorophyll. After hydrolysis from chlorophyll, free phytol is phosphorylated by the two kinases, and phytyl-diphosphate employed for the synthesis of tocopherol and phylloquinol. The reason why some chloroplast lipids, i.e. chlorophyll, tocopherol and phylloquinol, are derived from phytol, while others, i.e. carotenoids and tocotrienols (in some plant species) are synthesized from geranylgeraniol, remains unclear.
Topics: Phytol; Plants
PubMed: 30629961
DOI: 10.1016/j.plipres.2019.01.002 -
Chemico-biological Interactions Oct 2015This study aims to review phytol (PYT), through published articles, periodicals, magazines and patents, which were retrieved from the PM, SD, WS, SP; DII, WIPO, CIPO,... (Review)
Review
This study aims to review phytol (PYT), through published articles, periodicals, magazines and patents, which were retrieved from the PM, SD, WS, SP; DII, WIPO, CIPO, USPTO and INPI databases. Among the 149 articles and 62 patents, 27.52% articles and 87.09% patients were found on the searched topic, PYT and its sources and synthesis and metabolism; then followed by 15.44% and 14.77% articles on PYT in cytotoxicity/cancer/mutagenicity/teratogenicity and PYT in neurological diseases, respectively. In the pharma-medico viewpoint, PYT and its derivatives have been evident to have antimicrobial, cytotoxic, antitumorous, antimutagenic, anti-teratogenic, antibiotic-chemotherapeutic, antidiabetic, lipid lowering, antispasmodic, anticonvulsant, antinociceptive, antioxidant, anti-inflammatory, anxiolytic, antidepressant, immunoadjuvancy, hair growth facilitator, hair fall defense and antidandruff activities. Otherwise, the important biometebolite of PYT is phytanic acid (PA). Evidence shows PA to have cytotoxic, anticancer, antidiabetic, lipid lowering and aniteratogenic activities. In addition, it may be considered as an important biomarker for some diseases such as Refsum's Disease (RD), Sjögren Larsson syndrome (SLS), rhizomelic chondrodysplasia punctata (RZCP), chronic polyneuropathy (CP), Zellweger's disease hyperpipecolic academia (ZDHA) and related diseases. Thus, phytol may be considered as a new drug candidate.
Topics: Chemistry, Pharmaceutical; Databases as Topic; Humans; Patents as Topic; Phytol
PubMed: 26296761
DOI: 10.1016/j.cbi.2015.07.010 -
European Journal of Cancer Prevention :... Mar 2020This review summarizes the current evidence on the potential role of phytol, a microbial metabolite of chlorophyl A, and its metabolites, phytanic and pristanic acids,... (Review)
Review
This review summarizes the current evidence on the potential role of phytol, a microbial metabolite of chlorophyl A, and its metabolites, phytanic and pristanic acids, in carcinogenesis. Primary food sources in Western diets are the nut skin for phytol and lipids in dairy, beef and fish for its metabolites. Phytol and its metabolites gained interest as dietary compounds for cancer prevention because, as natural ligands of peroxisome proliferator-activated receptor-α and -γ and retinoid X receptor, phytol and its metabolites have provided some evidence in cell culture studies and limited evidence in animal models of anti-carcinogenic, anti-inflammatory and anti-metabolic-syndrome properties at physiological concentrations. However, there may be a narrow range of efficacy, because phytol and its metabolites at supra-physiological concentrations can cause in vitro cytotoxicity in non-cancer cells and can cause morbidity and mortality in animal models. In human studies, evidence for a role of phytol and its metabolites in cancer prevention is currently limited and inconclusive. In short, phytol and its metabolites are potential dietary compounds for cancer prevention, assuming the challenges in preventing cytotoxicity in non-cancer cells and animal models and understanding phytol metabolism can be mitigated.
Topics: Animals; Butter; Carcinogenesis; Diet Surveys; Diet, Western; Dietary Supplements; Disease Models, Animal; Fatty Acids; Feeding Behavior; Humans; Neoplasms; Nuts; PPAR alpha; PPAR gamma; Phytanic Acid; Phytol; Retinoid X Receptors; Risk Assessment
PubMed: 31436750
DOI: 10.1097/CEJ.0000000000000534 -
Cells Nov 2022Osteoporosis is a systemic skeletal disorder where osteoclasts are prevalent among osteoblasts. Oxidative stress is one of the main causes of osteoporosis, and nuclear...
Osteoporosis is a systemic skeletal disorder where osteoclasts are prevalent among osteoblasts. Oxidative stress is one of the main causes of osteoporosis, and nuclear factor erythroid-2-related factor 2 (Nrf2) is the master regulator of antioxidant responses. Phytol, a diterpene isolated from leaves, has many biological effects, including antimicrobial, antioxidant, and anti-inflammatory effects. This study investigated the crosstalk between Nrf2 and osteoclast differentiation in the presence of phytol. Phytol inhibited osteoclast differentiation through TRAP-positive and F-actin formation. The expression of anti-nuclear factor of activated T cells-c1 (NFATc1) and c-Fos was suppressed by phytol, as shown using Western blot and RT-PCR analysis. Phytol inhibited oxidative stress by suppressing reactive oxidant species (ROS) accumulation while recovering antioxidant enzymes, including superoxide dismutase and catalase. Additionally, phytol ameliorated osteoclast-specific differentiation, function, and oxidative stress through Nrf2 regulation by siRNA transfection. In conclusion, these data demonstrate the inhibitory effect of phytol on osteoclast differentiation through Nrf2 regulation, suggesting its potential use in oxidative stress-related osteoporosis and bone diseases.
Topics: Animals; Mice; Antioxidants; NF-E2-Related Factor 2; Osteoclasts; Osteoporosis; Oxidative Stress; Phytol; RAW 264.7 Cells
PubMed: 36429027
DOI: 10.3390/cells11223596 -
Nutrition Reviews Mar 2022Vitamin K is traditionally connected with blood coagulation, since it is needed for the posttranslational modification of 7 proteins involved in this cascade. However,... (Review)
Review
Vitamin K is traditionally connected with blood coagulation, since it is needed for the posttranslational modification of 7 proteins involved in this cascade. However, it is also involved in the maturation of another 11 or 12 proteins that play different roles, encompassing in particular the modulation of the calcification of connective tissues. Since this process is physiologically needed in bones, but is pathological in arteries, a great deal of research has been devoted to finding a possible link between vitamin K and the prevention of osteoporosis and cardiovascular diseases. Unfortunately, the current knowledge does not allow us to make a decisive conclusion about such a link. One possible explanation for this is the diversity of the biological activity of vitamin K, which is not a single compound but a general term covering natural plant and animal forms of vitamin K (K1 and K2) as well as their synthetic congeners (K3 and K4). Vitamin K1 (phylloquinone) is found in several vegetables. Menaquinones (MK4-MK13, a series of compounds known as vitamin K2) are mostly of a bacterial origin and are introduced into the human diet mainly through fermented cheeses. Current knowledge about the kinetics of different forms of vitamin K, their detection, and their toxicity are discussed in this review.
Topics: Animals; Humans; Kinetics; Osteoporosis; Vitamin K; Vitamin K 1; Vitamin K 2
PubMed: 34472618
DOI: 10.1093/nutrit/nuab061 -
Recent Patents on Biotechnology 2014Phytol (3,7,11,15-tetramethylhexadec-2-en-1-ol), a diterpene member of long and ramified chain of unsaturated acyclic alcohols. The objective of study was to conduct a... (Review)
Review
Phytol (3,7,11,15-tetramethylhexadec-2-en-1-ol), a diterpene member of long and ramified chain of unsaturated acyclic alcohols. The objective of study was to conduct a systematic review of this diterpene and its pharmaceutical applications in Nervous System diseases in humans and/or rodents. Periodicals bases, such as ScienceDirect and PubMed, were used, as well as technological basis of European Patent Office, World Intellectual Property Organization, United States Patent and Trademark Office, Derwent Innovations Index(®), Latin American Bank of Patents and data base of Instituto Nacional de Propriedade Industrial (INPI-National Institute of Industrial Property). The software EndNote-X5 was utilized as reference with the keywords: phytol, anxiolytic, antidepressant and anticonvulsant and their correlations in English, Spanish and Portuguese from January 2003 to June 2014. There are many publications on phytol in international literature. However, there is a reduced number of articles related to pharmacological activities proposed here. In reference to technological bases, patents present a wide range of pharmacological and commercial applications as cosmetics, hypolipodemic, anxiolytic and antidepressant. Therefore, it is necessary to explore phytol molecules, which present high pharmacological potential from scientific and technological points of view, in search of transference of technologies to generate economical and industrial growth.
Topics: Animals; Central Nervous System; Diterpenes; Humans; Patents as Topic; Phytol
PubMed: 27099143
DOI: 10.2174/187220830803150605162745 -
The Journal of Biological Chemistry 2021Phytol is the isoprenoid alcohol bound in ester linkage to chlorophyll, the most abundant photosynthetic pigment in plants. During leaf senescence, large amounts of...
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.
Topics: Arabidopsis; Chlorophyll; Hydrolysis; Phosphorylation; Photosynthesis; Phytol; Plant Leaves; Tocopherols
PubMed: 33713704
DOI: 10.1016/j.jbc.2021.100530 -
Nutritional Neuroscience Mar 2022Alzheimer's disease (AD) is an acquired neurological disorder of cognitive and behavioral impairments, with a long and progressive route. Currently, efforts are being...
Phytol loaded PLGA nanoparticles ameliorate scopolamine-induced cognitive dysfunction by attenuating cholinesterase activity, oxidative stress and apoptosis in Wistar rat.
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), β-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, 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.
Topics: Acetylcholinesterase; Amyloid Precursor Protein Secretases; Animals; Apoptosis; Aspartic Acid Endopeptidases; Butyrylcholinesterase; Cholinesterase Inhibitors; Cognitive Dysfunction; Nanoparticles; Neuroprotective Agents; Oxidative Stress; Phytol; Rats; Rats, Wistar; Scopolamine; Tissue Distribution
PubMed: 32406811
DOI: 10.1080/1028415X.2020.1764290 -
Journal of Ethnopharmacology Apr 2023Faeces Bombycis (silkworm excrement, called Cansha in Chinese), is the dried faeces of the larvae of silkworm. According to the theories of traditional Chinese medicine...
ETHNOPHARMACOLOGICAL RELEVANCE
Faeces Bombycis (silkworm excrement, called Cansha in Chinese), is the dried faeces of the larvae of silkworm. According to the theories of traditional Chinese medicine recorded in "Compendium of Materia Medica", Faeces Bombycis has often been prescribed in traditional Chinese medicine for the treatment of recurrent headache, rheumatalgia, rubella and itching et al. However, the bioactive components and their exact mechanisms underlying the pain-relieving effects remain to be revealed.
AIM OF THE STUDY
The present study aimed to evaluate the analgesic effect of Faeces Bombycis extract (FBE) on migraine, explore the main active constituents and investigate the pharmacological mechanisms for its pain relief.
MATERIALS AND METHODS
The bioactivity of different extracts from Faeces Bombycis was tracked by the nitroglycerin (NTG)-induced migraine model on rats and identified by NMR spectroscopic data. Whole-cell patch clamp technique, an electrophysiological method, was used to screen the potential targets and study the mechanism of action for the bioactive compound. The following targets have been screened and studied, including Nav1.7 sodium channels, Nav1.8 sodium channels, TRPV1 channels and TRPA1 channels. The trigeminal ganglion neurons were further used to study the effects of the identified compound on neuronal excitability.
RESULTS
By testing the bioactivity of the different extracts proceedingly, fraction petroleum ether showed higher anti-migraine activity. Through further step-by-step isolations, 7 compounds were isolated. Among them, phytol was identified with the highest yield and displayed a potent anti-migraine effect. By screening the potential ion channel targets for migraine, phytol was found to preferentially block the inactivated state of Nav1.7 sodium channels with half-inhibition concentration 0.32 ± 0.05 μM. Thus, the effects of phytol on the biophysical properties of Nav1.7 sodium channels were further characterized. Phytol induced a hyperpolarizing shift of voltage-dependent inactivation and slowed the recovery from inactivation. The affinity of phytol became weaker in the inactivation-deficient Nav1.7 channels (Nav1.7-WCW). And such an effect was independent on the local anesthetic site (Nav1.7 F1737A). Consistent with the data from recombinant channels, the compound also displayed state-dependent inhibition on neuronal sodium channels and further decreased the neuronal excitability in trigeminal ganglion neurons. Moreover, besides Nav1.7 channel, phytol also antagonized the activation of TRPV1 and TRPA1 channels at micromolar concentrations with a weaker affinity.
CONCLUSION
Our results demonstrated that phytol is the major anti-migraine ingredient of Faeces Bombycis and alleviates migraine behaviors by acting on Nav1.7 sodium channels in the trigeminal ganglion neurons. This study provided evidences for the therapeutic application of Faeces Bombycis and phytol on migraine disease.
Topics: Rats; Animals; Phytol; Sodium Channel Blockers; Pain; Sodium Channels; Neurons
PubMed: 36646158
DOI: 10.1016/j.jep.2023.116161 -
Annual Review of Nutrition 1995Vitamin K is the blood-clotting vitamin. The mechanism of action of vitamin K is discussed in terms of a new carbanion model that mimics the proton abstraction from the... (Review)
Review
Vitamin K is the blood-clotting vitamin. The mechanism of action of vitamin K is discussed in terms of a new carbanion model that mimics the proton abstraction from the gamma position of protein-bound glutamate. This is the essential step leading to carboxylation and activation of the blood-clotting proteins. The model comprises an oxygenation that is coupled to carbon-carbon bond formation, as is the oxygenation of vitamin K hydroquinone to vitamin K oxide. The model hypothesis is also supported by the mechanism of inhibition of the carboxylase by HCN, which acts as an acid-base inhibitor rather than a metal-complexing inhibitor. The new model postulates a dioxetane intermediate that explains the presence of a second atom of 18O (from 18O2) incorporated into vitamin K oxide in the course of the enzymatic carboxylation. Finally, the chemistry developed here has been used to define the active site of vitamin K hydroquinone as the carbon-carbon bond adjacent to the methyl group.
Topics: Animals; Blood Coagulation; Calcium; Humans; Vitamin K
PubMed: 8527228
DOI: 10.1146/annurev.nu.15.070195.002223