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Profiles of Drug Substances,... 2013This chapter includes the aspects of Menadione (vitamin K). The drug is synthesized by the use of itaconic acid obtained through Friedel-Craft condensation or by direct... (Review)
Review
This chapter includes the aspects of Menadione (vitamin K). The drug is synthesized by the use of itaconic acid obtained through Friedel-Craft condensation or by direct oxidation of the 2-methyl-1,4-naphthquinone. Vitamin K generally maintains healthy blood clotting and prevents excessive bleeding and hemorrhage, it is also important for maintaining healthy bone structure and for carbohydrate storage in the body. In addition, it is given to newborn babies born in hospitals to prevent the development of life-threatening bleeding caused by low prothrombin levels. The chapter discusses the drug metabolism and pharmacokinetics and presents various method of analysis of this drug such as compendial tests, electrochemical analysis, spectroscopic analysis, and chromatographic techniques of separation. It also discusses its physical properties such as solubility characteristics, X-ray powder diffraction pattern, and thermal methods of analysis. The chapter is concluded with a discussion on its biological properties such as activity, toxicity, and safety.
Topics: Animals; Drug Stability; Humans; Solubility; Spectrum Analysis; Vitamin K 3
PubMed: 23668406
DOI: 10.1016/B978-0-12-407691-4.00006-X -
Environmental Science and Pollution... Jul 2023Phytol (Pyt), a diterpenoid, possesses many important bioactivities. This study evaluates the anticancer effects of Pyt on sarcoma 180 (S-180) and human leukemia (HL-60)...
Phytol (Pyt), a diterpenoid, possesses many important bioactivities. This study evaluates the anticancer effects of Pyt on sarcoma 180 (S-180) and human leukemia (HL-60) cell lines. For this purpose, cells were treated with Pyt (4.72, 7.08, or 14.16 μM) and a cell viability assay was performed. Additionally, the alkaline comet assay and micronucleus test with cytokinesis were also performed using doxorubicin (6 μM) and hydrogen peroxide (10 mM) as positive controls and stressors, respectively. Results revealed that Pyt significantly reduced the viability and rate of division in S-180 and HL-60 cells with IC values of 18.98 ± 3.79 and 1.17 ± 0.34 μM, respectively. Pyt at 14.16 μM exerted aneugenic and/or clastogenic effects in S-180 and HL-60 cells, where the number of micronuclei and other nuclear abnormalities (e.g., nucleoplasmic bridges and nuclear buds) were frequently observed. Moreover, Pyt at all concentrations induced apoptosis and showed necrosis at 14.16 μM, suggesting its anticancer effects on the tested cancer cell lines. Taken together, Pyt showed promising anticancer effects, possibly through inducing apoptosis and necrosis mechanisms, and it exerted aneugenic and/or clastogenic effects on the S-180 and HL-60 cell lines.
Topics: Animals; Humans; HL-60 Cells; Sarcoma 180; Phytol; Apoptosis; Necrosis; Micronucleus Tests; Sarcoma
PubMed: 37308630
DOI: 10.1007/s11356-023-28036-4 -
Inflammopharmacology Aug 2019This study is aimed at the evaluation of antipyretic effect of PHY in yeast-induced hyperthermia rats. Additionally, possible mechanism of antipyretic action of PHY has...
AIMS
This study is aimed at the evaluation of antipyretic effect of PHY in yeast-induced hyperthermia rats. Additionally, possible mechanism of antipyretic action of PHY has been also studied by molecular docking study.
METHODS
Adult male Wistar albino rats were treated with PHY at 100, 150 and 200 mg/kg in 0.05% Tween-80 dissolved in 0.9% NaCl solution. PHY was also given at 200 mg/kg with ibuprofen (IBU) 12.5 mg/kg (p.o.) or paracetamol (PARA) 100 mg/kg (p.o.) to see the combined effect of PHY in animals. In silico study of PHY was performed against cyclooxygenase (COX) enzymes (COX-1 and -2) proteins.
RESULTS
PHY exhibited the antipyretic effect in febrile rats in a dose and time dependent manner. PHY 200 mg/kg co-treated with IBU12.5 or PARA100 exhibited greater antipyretic effect than the PHY or NSAIDs individual groups. Data from the computational study reveal that 5KIR of COX-2 is the most efficient receptor protein to which PHY interacts.
CONCLUSION
PHY attributed an antipyretic effect, possibly via 5KIR-dependent COX-2 inhibition pathway.
Topics: Acetaminophen; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antipyretics; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Fever; Ibuprofen; Male; Phytol; Rats; Rats, Wistar
PubMed: 30778877
DOI: 10.1007/s10787-019-00574-9 -
Biomedicine & Pharmacotherapy =... Sep 2018In the present study, the antiproliferative activity of phytol and its mechanism of action against human lung adenocarcinoma cell line A549 were studied in detail....
In the present study, the antiproliferative activity of phytol and its mechanism of action against human lung adenocarcinoma cell line A549 were studied in detail. Results showed that phytol exhibited potent antiproliferative activity against A549 cells in a dose and time-dependent manner with an IC value of 70.81 ± 0.32 μM and 60.7 ± 0.47 μM at 24 and 48 h, respectively. Phytol showed no adverse toxic effect in normal human lung cells (L-132), but mild toxic effect was observed when treated with maximum dose (67 and 84 μM). No membrane-damaging effect was evidenced by PI staining and SEM analysis. The results of mitochondrial membrane potential analysis, cell cycle analysis, FT-IR and Western blotting analysis clearly demonstrated the molecular mechanism of phytol as induction of apoptosis in A549 cells, as evidenced by formation of shrinked cell morphology with membrane blebbing, depolarization of mitochondrial membrane potential, increased cell population in the sub-G0 phase, band variation in the DNA and lipid region, downregulation of Bcl-2, upregulation of Bax and the activation of caspase-9 and -3. In addition, phytol inhibited the CAM vascular growth as evidenced by CAM assay, which positively suggests that phytol has anti-angiogenic potential. Taken together, these findings clearly demonstrate the mode of action by which phytol induces cell death in A549 lung adenocarcinoma cells.
Topics: A549 Cells; Angiogenesis Inhibitors; Apoptosis; Cell Cycle; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Humans; Membrane Potential, Mitochondrial; Phytol; Time Factors
PubMed: 29908495
DOI: 10.1016/j.biopha.2018.06.035 -
Archives of Pharmacal Research Oct 2002The succinic semialdehyde dehydrogenase (SSADH) inhibitory component was isolated from the EtOAc fraction of Lactuca sativa through repeated column chromatography; then,...
The succinic semialdehyde dehydrogenase (SSADH) inhibitory component was isolated from the EtOAc fraction of Lactuca sativa through repeated column chromatography; then, it was identified as phytol, a diterpenoid, based on the interpretation of several spectral data. Incubation of SSADH with the phytol results in a time-dependent loss of enzymatic activity, suggesting that enzyme modification is irreversible. The inactivation followed pseudo-first-order kinetics with the second-rate order constant of 6.15 x 10(-2) mM(-1) min(-1). Complete protection from inactivation was afforded by the coenzyme NAD+, whereas substrate succinic semialdehyde failed to prevent the inactivation of the enzyme; therefore, it seems likely that phytol covalently binds at or near the active site of the enzyme. It is postulated that the phytol is able to elevate the neurotransmitter GABA levels in central nervous system through its inhibitory action on one of the GABA degradative enzymes, SSADH.
Topics: Aldehyde Oxidoreductases; Animals; Cattle; Diterpenes; Enzyme Inhibitors; Lactuca; Phytol; Plant Components, Aerial; Plant Extracts; Succinate-Semialdehyde Dehydrogenase
PubMed: 12433198
DOI: 10.1007/BF02976937 -
Free Radical Research Dec 2016Phytol, isolated from Aster yomena, is widely distributed as a constituent of chlorophyll. In the present study, we confirmed the antibacterial activity of phytol and...
Phytol, isolated from Aster yomena, is widely distributed as a constituent of chlorophyll. In the present study, we confirmed the antibacterial activity of phytol and its mechanism inducing oxidative cell death in Pseudomonas aeruginosa. In phytol-treated cells, elevated level of intracellular reactive oxygen species (ROS) and transient NADH depletion were observed. These results demonstrated that phytol induced ROS accumulation and that the electron transport chain was involved in increase of ROS. Due to this ROS generation, the imbalance developed between intracellular ROS and the antioxidant defense system, leading to decrease of reduced glutathione (GSH). Moreover, severe DNA damage was shown after treatment with phytol. DNA electrophoresis and a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were conducted with pretreatment with the antioxidant N-acetylcysteine (NAC) to evaluate the cause of DNA damage. In NAC-pretreated cells, alleviated damage was confirmed and it supports that phytol induces oxidative stress-mediated DNA damage. In conclusion, phytol exerts the antibacterial property via inducing oxidative stress response in P. aeruginosa.
Topics: Anti-Bacterial Agents; Apoptosis; DNA Damage; Oxidative Stress; Phytol; Pseudomonas aeruginosa
PubMed: 27667264
DOI: 10.1080/10715762.2016.1241395 -
Cellular and Molecular Biology... Jun 2020Phytol (PHY) is an acyclic natural diterpene alcohol and a chlorophyll constituent that exhibits several pharmacological effects, such as anticancer, antioxidant, and...
Phytol (PHY) is an acyclic natural diterpene alcohol and a chlorophyll constituent that exhibits several pharmacological effects, such as anticancer, antioxidant, and antimicrobial. Here, we aimed to assess the PHY anti-inflammatory effect in vitro and in vivo, and to deepen knowledge on the possible mechanism of action. For this purpose, egg albumin (in vitro) test was performed by using acetyl salicylic acid (ASA) as a standard nonsteroidal anti-inflammatory drugs (NSAID). For in vivo test, male Wistar albino rats were treated (intraperitoneally) with 100 mg/kg of PHY and/or standard NSAIDs ASA (100 mg/kg) and diclofenac sodium (Diclo-Na, 10 mg/kg) to evaluate the combined effect of PHY in formalin-induced paw edema model. Furthermore, an in silico (CADD) study was accomplished to assess the effect of PHY against cyclooxygenase (COX)-1 and 2 enzymes, nuclear factor kappa B (NF-κB), and interleukin-1β (IL-1β). Results revealed that PHY exhibits dose-dependent anti-inflammatory effect using the egg albumin method. PHY (100 mg/kg) co-treated with ASA and/or Diclo-Na reduced paw edema better than PHY alone or NSAIDs individual groups. Computational study showed that PHY efficiently interacts with COX-1 and 2, NF-κB, and IL-1β. In conclusion, PHY exhibits anti-inflammatory activity, possibly via COX-1 and 2, NF-κB, and IL-1β dependent pathways.
Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Edema; Male; Molecular Docking Simulation; Ovalbumin; Phytol; Rats, Wistar
PubMed: 32583784
DOI: No ID Found -
Food and Chemical Toxicology : An... May 2018The phytol isolated from watermelon (Citrullus lanatus) sprouts inhibited the growth of a human T-cell leukemia line Jurkat cell and suppressed tumor progression in a...
The phytol isolated from watermelon (Citrullus lanatus) sprouts inhibited the growth of a human T-cell leukemia line Jurkat cell and suppressed tumor progression in a xenograft model of human lung adenocarcinoma epithelial cell line A549 in nude mice. To elucidate the mechanisms underlying the phytol-induced cell death in the present study, we examined the changes in cell morphology, DNA fragmentation, and intracellular reactive oxygen species (ROS) levels and performed flow cytometric analysis to evaluate cell cycle stage. There were no significant changes in apoptosis, autophagy, and necrosis marker in cells treated with the phytol. But, we found, for the first time, that phytol remarkably induced S-phase cell cycle arrest accompanied with intracellular ROS production. Western blot analyses showed that phytolinduced S-phase cell cycle arrest was mediated through the decreased expression of cyclins A and D and the downregulations of MAPK and PI3K/Akt. The tumor volume levels in mice treated with phytol were lower than those of non-treatment groups, and it showed very similar suppression compared with those of mice treated with cyclophosphamide. Based on the data of in vitro and in vivo studies and previous studies, we suggest phytol as a potential therapeutic compound for cancer.
Topics: A549 Cells; Acetylcysteine; Animals; Antineoplastic Agents, Phytogenic; Blotting, Western; Cell Death; Citrullus; Cyclins; DNA Fragmentation; Enzyme Inhibitors; Humans; Jurkat Cells; Mice; Mice, Nude; NADPH Oxidases; Phytol; Protein Kinases; Reactive Oxygen Species; S Phase
PubMed: 29608981
DOI: 10.1016/j.fct.2018.03.033 -
PLoS Neglected Tropical Diseases 2014Schistosomiasis is a major endemic disease that affects hundreds of millions worldwide. Since the treatment and control of this parasitic disease rely on a single drug,...
BACKGROUND
Schistosomiasis is a major endemic disease that affects hundreds of millions worldwide. Since the treatment and control of this parasitic disease rely on a single drug, praziquantel, it is imperative that new effective drugs are developed. Here, we report that phytol, a diterpene alcohol from chlorophyll widely used as a food additive and in medicinal fields, possesses promising antischistosomal properties in vitro and in a mouse model of schistosomiasis mansoni.
METHODS AND FINDINGS
In vitro, phytol reduced the motor activity of worms, caused their death and confocal laser scanning microscopy analysis showed extensive tegumental alterations in a concentration-dependent manner (50 to 100 µg/mL). Additionally, phytol at sublethal doses (25 µg/mL) reduced the number of Schistosoma mansoni eggs. In vivo, a single dose of phytol (40 mg/kg) administered orally to mice infected with adult S. mansoni resulted in total and female worm burden reductions of 51.2% and 70.3%, respectively. Moreover, phytol reduced the number of eggs in faeces (76.6%) and the frequency of immature eggs (oogram pattern) was significantly reduced. The oogram also showed increases in the proportion of dead eggs. Confocal microcopy studies revealed tegumental damage in adult S. mansoni recovered from mice, especially in female worms.
CONCLUSIONS
The significant reduction in parasite burden by this chlorophyll molecule validates phytol as a promising drug and offers the potential of a new direction for chemotherapy of human schistosomiasis. Phytol is a common food additive and nonmutagenic, with satisfactory safety. Thus, phytol has potential as a safe and cost-effective addition to antischistosomal therapy.
Topics: Administration, Oral; Animals; Anthelmintics; Disease Models, Animal; Female; Locomotion; Mice; Mice, Inbred BALB C; Parasite Load; Parasitic Sensitivity Tests; Phytol; Schistosoma mansoni; Schistosomiasis mansoni; Survival Analysis
PubMed: 24392173
DOI: 10.1371/journal.pntd.0002617 -
Food & Function Apr 2018Stimulating the browning of white adipocytes contributes to the restriction of obesity and related metabolic disorders. This study aimed to investigate the browning...
Stimulating the browning of white adipocytes contributes to the restriction of obesity and related metabolic disorders. This study aimed to investigate the browning effects of phytol on mice inguinal subcutaneous white adipose tissue (iWAT) and explore the underlying mechanisms. Our results demonstrated that phytol administration decreased body weight gain and iWAT index, and stimulated the browning of mice iWAT, with the increased expression of brown adipocyte marker genes (UCP1, PRDM16, PGC1α, PDH, and Cyto C). In addition, phytol treatment activated the AMPKα signaling pathway in mice iWAT. In good agreement with the in vivo findings, the in vitro results showed that 100 μM phytol stimulated brown adipogenic differentiation and formation of brown-like adipocytes in the differentiated 3T3-L1 by increasing the mitochondria content and oxygen consumption, and promoting mRNA and/or protein expression of brown adipocyte markers (UCP1, PRDM16, PGC1α, PDH, Cyto C, Cidea and Elovl3) and beige adipocyte markers (CD137 and TMEM26). Meanwhile, phytol activated the AMPKα signaling pathway in the differentiated 3T3-L1. However, the inhibition of AMPKα with Compound C totally abolished phytol-stimulated brown adipogenic differentiation and formation of brown-like adipocytes. In conclusion, these results showed that phytol stimulated the browning of mice iWAT, which was coincident with the increased formation of brown-like adipocytes in the differentiated 3T3-L1, and appeared to be primarily mediated by the AMPKα signaling pathway. These data provided new insight into the role of phytol in regulating the browning of WAT and suggested the potential application of phytol as a nutritional intervention for the restriction of obesity and related metabolic disorders.
Topics: 3T3-L1 Cells; AMP-Activated Protein Kinases; Adipocytes, Beige; Adipogenesis; Adiposity; Animals; Anti-Obesity Agents; Biomarkers; Diet, High-Fat; Dietary Supplements; Enzyme Activation; Gene Expression Regulation, Developmental; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Obesity; Phytol; Protein Kinase Inhibitors; Random Allocation; Signal Transduction; Subcutaneous Fat, Abdominal
PubMed: 29570193
DOI: 10.1039/C7FO01817G