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Brain Research Feb 2014Phytol, a branched chain unsaturated alcohol, is particularly interesting because it is an isolated compound from essential oils of different medicinal plants. The aim...
Phytol, a branched chain unsaturated alcohol, is particularly interesting because it is an isolated compound from essential oils of different medicinal plants. The aim of this study was to evaluate the anxiolytic-like effects of phytol in animal models to clarify their possible action mechanism. After acute intraperitoneal treatment with phytol at doses of 25, 50 and 75 mg/kg behavioral models of open-field, elevated-plus-maze, rota-rod, light-dark, marble-burying and pentobarbital sleeping time tests were utilized. In open field test, phytol (25, 50 and 75 mg/kg) [p<0.01] increased the number of crossings and rearings. However, the number of groomings [p<0.01] was reduced. Likewise, the number of entries and the time spent in light space were increased [p<0.01] while the number of marble-burying was decreased [p<0.001], in elevated-plus-maze, light-dark and marble-burying tests, respectively. In motor activity test, phytol (75 mg/kg) impaired the rota-rod performance of mice [p<0.01]. In pentobarbital sleeping time test, phytol 75 mg/kg decreased for latency of sleeping and phytol (25, 50 and 75 mg/kg) increased the sleep time when compared to negative control [p<0.05]. All these effects were reversed by pre-treatment with flumazenil (2.5mg/kg, i.p.), similarly to those observed with diazepam (2mg/kg, i.p.; positive control) suggesting that the phytol presents mechanism of action by interaction with the GABAergic system. These findings suggest that acute administration of phytol exerts an anxiolytic-like effect on mice. Furthermore, suppose that phytol interacts with GABAA receptor, probably at the receptor subtypes that mediate benzodiazepines effects, to produce sedative and anxiolytic activities.
Topics: Animals; Anti-Anxiety Agents; Behavior, Animal; Flumazenil; GABA Modulators; Male; Maze Learning; Mice; Motor Activity; Phytol; Sleep
PubMed: 24333358
DOI: 10.1016/j.brainres.2013.12.003 -
Artificial Cells, Nanomedicine, and... Dec 2018Alzheimer's disease (AD) is an unfavourable neurological condition of the brain leading to the loss of behavioural and cognitive skills of the aging population. At...
Alzheimer's disease (AD) is an unfavourable neurological condition of the brain leading to the loss of behavioural and cognitive skills of the aging population. At present, drugs representing cholinesterase inhibitors provide lateral side effects to AD patients. Hence, there is a need for improved fabrication of drugs without side effects, for which nanoencapsulated bioactive compounds that can cross the blood-brain barrier offer new hope as novel alternative treatment strategy for AD. This study involved synthesis of phytol loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles by solvent evaporation method. Physico-chemical characterization of phytol-PLGA NPs through the field emission scanning electron microscope, dynamic laser scattering (DLS) measurement revealed that the particles were nanosize range with smooth surface and spherical morphology. Furthermore, the biocompatibility of drug/polymer ratio was investigated by power X-ray diffraction (PXRD) and Fourier-transform infrared spectroscopic (FT-IR) analysis. The in vitro drug release study showed that the phytol was released in a sustained manner. Moreover, phytol-PLGA NPs were able to disrupt amyloid aggregates, exhibit anti-cholinesterase and anti-oxidative property and are non-cytotoxic in Neuro2a cells.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Cell Line; Delayed-Action Preparations; Humans; Nanoparticles; Neurons; Phytol; Polylactic Acid-Polyglycolic Acid Copolymer; Protein Aggregates
PubMed: 29069924
DOI: 10.1080/21691401.2017.1391822 -
Experimental Parasitology Sep 2020The search for novel therapeutic candidates against animal trypanosomiasis is an ongoing scientific endevour because of the negative impacts of the disease to the...
The search for novel therapeutic candidates against animal trypanosomiasis is an ongoing scientific endevour because of the negative impacts of the disease to the African livestock industry. In this study, the in vivo therapeutic potentials of phytol toward Trypanosoma congolense infection and the inhibitory effects on trypanosomal sialidase were investigated. Rats were infected with T. congolense and administered daily oral treatment of 50 and 100 mg/kg BW of phytol. Within the first 10 days of the treatment, no antitrypanosomal activity was recorded but a moderate trypanostatic activity was observed from day 17-day 21 pi. However, at 100 mg/kg BW, phytol demonstrated a significant (p < 0.05) ameliorative potentials toward T. congolense-induced host-associated pathological damages such as anaemia, hepatic and renal damages; and the data was comparable to diminazine aceturate. Moreover, the T. congolense caused a significant (p < 0.05) increase in free serum sialic acid level which was significantly (p < 0.05) prevented in the presence of phytol (100 mg/kg BW). In an in vitro analysis, phytol inhibited partially purified T. congolense sialidase using an uncompetitive inhibition pattern with inhibition binding constant of 261.24 μmol/mL. Subsequently, molecular docking revealed that the compound binds to homology modelled trypanosomal sialidase with a binding free energy of -6.7 kcal/mol which was mediated via a single hydrogen bond while Trp324 and Pro274 were the critical binding residues. We concluded that phytol has moderate trypanostatic activity but with a great potential in mitigating the host-associated cellular damages while the anaemia amelioration was mediated, in part, through the inhibition of sialidase.
Topics: Animals; Antiprotozoal Agents; Enzyme Inhibitors; Livestock; Neglected Diseases; Neuraminidase; Phytol; Random Allocation; Rats; Rats, Wistar; Trypanosoma congolense; Trypanosomiasis, African
PubMed: 32598890
DOI: 10.1016/j.exppara.2020.107943 -
Biotechnology and Applied Biochemistry Dec 2022Cancer incidences are growing rapidly and causing millions of deaths globally. Cancer treatment is one of the most exigent challenges. Drug resistance is a natural... (Review)
Review
Cancer incidences are growing rapidly and causing millions of deaths globally. Cancer treatment is one of the most exigent challenges. Drug resistance is a natural phenomenon and is considered one of the major obstacles in the successful treatment of cancer by chemotherapy. Combination therapy by the amalgamation of various anticancer drugs has suggested modulating tumor response by targeting various signaling pathways in a synergistic or additive manner. Vitamin K is an essential nutrient and has recently been investigated as a potential anticancer agent. The combination of vitamin K analogs, such as vitamins K1, K2, K3, and K5, with other chemotherapeutic drugs have demonstrated a safe, cost-effective, and most efficient way to overcome drug resistance and improved the outcomes of prevailing chemotherapy. Published reports have shown that vitamin K in combination therapy improved the efficacy of clinical drugs by promoting apoptosis and cell cycle arrest and overcoming drug resistance by inhibiting P-glycoprotein. In this review, we discuss the mechanism, cellular targets, and possible ways to develop vitamin K subtypes into effective cancer chemosensitizers. Finally, this review will provide a scientific basis for exploiting vitamin K as a potential agent to improve the efficacy of chemotherapeutic drugs.
Topics: Humans; Vitamin K; Vitamin K 3; Vitamin K 2; Neoplasms; Vitamin K 1; Antineoplastic Agents
PubMed: 34993998
DOI: 10.1002/bab.2312 -
Biomedicine & Pharmacotherapy =... Aug 2017A number of drugs as well as lead molecules are isolated from natural sources. Phytol is one of such lead molecule belongs to terpenes group distributed widely in...
Phytol induces ROS mediated apoptosis by induction of caspase 9 and 3 through activation of TRAIL, FAS and TNF receptors and inhibits tumor progression factor Glucose 6 phosphate dehydrogenase in lung carcinoma cell line (A549).
A number of drugs as well as lead molecules are isolated from natural sources. Phytol is one of such lead molecule belongs to terpenes group distributed widely in medicinal plants. In the present work, we investigated the cytotoxic behavior of phytol on human lung carcinoma cells (A549). Phytol was found to cause characteristic apoptotic morphological changes and generation of ROS in A549 cells. The mechanism of phytol involved the activation of TRAIL, FAS and TNF-α receptors along with caspase 9 and 3. In silico molecular docking studies revealed that phytol has a good binding affinity with glucose-6-phosphate dehydrogenase (G6PD), which is known to promote tumor proliferation. The ability of phytol to become potential drug candidate has been revealed from the pharmacokinetic study performed in the present study.
Topics: A549 Cells; Apoptosis; Caspase 3; Caspase 9; Cell Line, Tumor; Enzyme Induction; Glucosephosphate Dehydrogenase; Humans; Lung Neoplasms; Phytol; Protein Structure, Secondary; Reactive Oxygen Species; Receptors, TNF-Related Apoptosis-Inducing Ligand; Receptors, Tumor Necrosis Factor; fas Receptor
PubMed: 28575806
DOI: 10.1016/j.biopha.2017.05.066 -
Fundamental & Clinical Pharmacology Aug 2014Studies have shown that diterpenes have anti-inflammatory and redox-protective pharmacological activities. The present study aimed to investigate the anti-inflammatory...
Studies have shown that diterpenes have anti-inflammatory and redox-protective pharmacological activities. The present study aimed to investigate the anti-inflammatory properties of phytol, a diterpene alcohol, in a mouse model of acute inflammation, and phytol effect on leukocyte recruitment, cytokines levels, and oxidative stress. The anti-inflammatory activities of phytol were assessed by measuring paw edema induced by different inflammatory agents (e.g., λ-carrageenan, compound 48/80, histamine, serotonin, bradykinin, and prostaglandin E2 [PGE2 ]), myeloperoxidase (MPO) activity, peritonitis model and cytokine levels. Further, oxidative stress was evaluated by determining glutathione (GSH) levels and malondialdehyde (MDA) concentration. The results showed that phytol (7.5, 25, 50, and 75 mg/kg) significantly reduced carrageenan-induced paw edema, in a dose-dependent manner. In addition, phytol (75 mg/kg) inhibited compound 48/80-, histamine-, serotonin-, bradykinin- and PGE2 -induced paw edema. It also inhibited the recruitment of total leukocytes and neutrophils; decreased MPO activity, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels, and MDA concentration; and increased GSH levels during carrageenan-induced acute inflammation. These results suggest that phytol attenuates the inflammatory response by inhibiting neutrophil migration that is partly caused by reduction in IL-1β and TNF-α levels and oxidative stress.
Topics: Animals; Anti-Inflammatory Agents; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Glutathione; Inflammation; Interleukin-1beta; Leukocytes; Male; Malondialdehyde; Mice; Neutrophils; Oxidative Stress; Peroxidase; Phytol; Tumor Necrosis Factor-alpha
PubMed: 24102680
DOI: 10.1111/fcp.12049 -
Neuroscience Letters Aug 2012The present study investigated the effects of phytol in pilocarpine-induced seizures. The latency for development of convulsions and mortality rate was recorded in this...
The present study investigated the effects of phytol in pilocarpine-induced seizures. The latency for development of convulsions and mortality rate was recorded in this model using mice. The results revealed that phytol (25, 50 and 75 mg/kg, i.p.) increased latency to first seizure and decreased percentage of these seizures. Moreover, phytol also protected the animals against status epilepticus induced by pilocarpine, and decreased the mortality rate. Mice treated with pilocarpine (n=24) presented 100% of mortality during the first hour of observation. In turn, phytol-pretreated animals within 30 min before the administration of pilocarpine (400 mg/kg) remained alive during the first hour of observation. On the other hand, 6-8h after administration of pilocarpine it was observed that 10 (41.66%), 8 (33.33%) and 4 (16.66%) animals died (respectively). Thus, the pretreatment with phytol was able to block mortality rate during the first hour in acute phase of seizures, and significantly reduced this rate in a dose-dependent manner (p<0.05), suggesting an anticonvulsant effect. In addition, none of the phytol effects was blocked by pre-treatment with flumazenil, an antagonist of benzodiazepine receptors. In conclusion, phytol exhibits anticonvulsant activity by modulating of neurotransmitter systems, but further investigations are in progress to confirm this pharmacological property.
Topics: Animals; Anticonvulsants; Male; Mice; Phytol; Pilocarpine; Seizures; Status Epilepticus; Survival Rate
PubMed: 22750154
DOI: 10.1016/j.neulet.2012.06.055 -
Microbial Pathogenesis Dec 2021Phytocompounds have long been well recognized in medicine and pharmacy. The natural compounds are frequently utilized as the fundamental resource in the development of...
Phytocompounds have long been well recognized in medicine and pharmacy. The natural compounds are frequently utilized as the fundamental resource in the development of novel therapeutic agents to treat bacterial infections. The rapid emergence of bacterial infections, particularly caused by Vibrio species, is seen as a serious concern for the development of aquaculture industries, resulting in substantial economic losses throughout the world. Notably, the presence of Vibrio campbellii in aquatic environments will be extremely problematic, leading to significant mortality in aquatic organisms. As a result, novel therapeutic agents are desperately needed to treat such diseases. This is the first research to demonstrate that plant-derived active compounds, tocopherol and phytol, are effective against V. campbellii infection in tomato clownfish. The findings showed that tocopherol and phytol significantly decreased the production of biofilm and virulence factors such as hemolysin, protease, lipase, hydrophobic index, and swimming motility in V. campbellii, without influencing the bacterial growth. In vivo experiments with tomato clownfish also proved that these phytocompound treatments significantly increased the survival rates of infected fishes by hindering the intestinal colonization of V. campbellii in tomato clownfish. Further, the disease protection efficacy against the pathognomonic sign of V. campbellii-infection was verified by histopathological investigation of the gills, gut, and kidney. Altogether, the results suggest that tocopherol and phytol could be promising therapeutic agents for the treatment of V. campbellii infections in aquaculture.
Topics: Animals; Aquaculture; Phytol; Quorum Sensing; Tocopherols; Vibrio
PubMed: 34627940
DOI: 10.1016/j.micpath.2021.105221 -
Progress in the Chemistry of Fats and... 1978
Review
Topics: Animals; Ants; Bees; Chlorophyll; Chlorophyllides; Chromatography, Gas; Diterpenes; Esterification; Isomerism; Mass Spectrometry; Membranes; Phytol; Plants; Spectrophotometry, Infrared
PubMed: 358266
DOI: 10.1016/0079-6832(78)90046-0 -
Medicinal Chemistry (Shariqah (United... 2022Due to the prevalence of type-2 diabetes across the globe, there is an unmet need to explore new molecular targets for the development of cost-effective and safer...
BACKGROUND
Due to the prevalence of type-2 diabetes across the globe, there is an unmet need to explore new molecular targets for the development of cost-effective and safer antihyperglycemic agents.
OBJECTIVE
Structural modification of phytol and evaluation of in vitro, in vivo and in silico antihyperglycemic activity of derivatives establishing the preliminary structure activity relationship (SAR).
METHODS
The semi-synthetic derivatives of phytol were prepared following previously described methods. The antihyperglycemic potential was measured in vitro in terms of increase in 2- deoxyglucose (2-DG) uptake by L-6 rat skeletal muscle cells as well as in vivo in sucrose-loaded (SLM) and streptozotocin (STZ)-induced diabetic rat models. The blood glucose profile was measured at 30, 60, 90, 120, 180, 240, 300 and 1440 min post administration of sucrose in rats. The in silico docking was performed on peroxisome proliferator-activated receptor gamma (PPARγ) as antidiabetic target along with absorption, distribution, metabolism, excretion and toxicity (ADMET) studies.
RESULTS
Nine semi-synthetic ester derivatives: acetyl (1), lauroyl (2), palmitoyl (3), pivaloyl (4), trans-crotonyl (5), benzoyl (6), m-anisoyl (7), 3,4,5-trimethoxy benzoyl (8) cinnamoyl (9) along with bromo derivative (10) of phytol were prepared. The derivatives 9, 8 and 2 caused 4.5, 3.2 and 2.7 times more in vitro uptake of 2-DG respectively than rosiglitazone (ROSI). The derivatives showed significant improvement in oral glucose tolerance both in SLM (29.6-21%) as well as STZ-induced diabetic (30.8-19.0%) rats. The in silico ADMET, docking studies showed non-toxicity and high binding affinity with PPARγ.
CONCLUSION
The potent antihyperglycemic activity with favorable pharmacokinetics supports phytol derivatives as a suitable antidiabetic lead.
Topics: Animals; Blood Glucose; Hypoglycemic Agents; Phytol; Rats; Rosiglitazone; Streptozocin
PubMed: 33327922
DOI: 10.2174/1573406417666201216124018