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Experimental Parasitology May 2021The 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...
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.
Topics: Analysis of Variance; Anemia; Animals; Antimalarials; Brain; Chloroquine; Dose-Response Relationship, Drug; Female; Hematocrit; Liver; Malaria; Male; Mice; Oxidation-Reduction; Parasitemia; Phytol; Plasmodium berghei; Random Allocation; Spleen
PubMed: 33736972
DOI: 10.1016/j.exppara.2021.108097 -
Nutrients Jun 2023Vitamin K and vitamin K-dependent proteins have been reported to be associated with a large spectrum of age-related diseases. While most of these associations have been... (Review)
Review
Vitamin K and vitamin K-dependent proteins have been reported to be associated with a large spectrum of age-related diseases. While most of these associations have been deduced from observational studies, solid evidence for the direct impact of vitamin K on cellular senescence remains to be proven. As vitamin K status reflects the complexity of interactions between dietary intake, gut microbiome activity and health, we will demonstrate the pivotal role of the diet-microbiome-health axis in human ageing and exemplify how vitamin K is implicated therein. We propose that food quality (i.e., food pattern) should be highlighted beyond the quantity of total vitamin K intake. Instead of focusing on a single nutrient, exploring a healthy diet containing vitamin K may be more strategic. As such, healthy eating patterns can be used to make dietary recommendations for the public. Emerging evidence suggests that dietary vitamin K is a modulator of the diet-microbiome-health axis, and this needs to be incorporated into the investigation of the impact of vitamin K on gut microbial composition and metabolic activities, along with host health outcomes. In addition, we highlight several critical caveats that need to be acknowledged regarding the interplay between diet, vitamin K, gut microbiome and host health that is pivotal for elucidating the role of vitamin K in ageing and responding to the urgent call of healthy eating concerning public health.
Topics: Humans; Gastrointestinal Microbiome; Vitamin K; Diet; Feeding Behavior; Aging
PubMed: 37375631
DOI: 10.3390/nu15122727 -
Archives of Osteoporosis Jun 2023This study assessed whether vitamin K, given with oral bisphosphonate, calcium and/or vitamin D has an additive effect on fracture risk in post-menopausal women with... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
This study assessed whether vitamin K, given with oral bisphosphonate, calcium and/or vitamin D has an additive effect on fracture risk in post-menopausal women with osteoporosis. No difference in bone density or bone turnover was observed although vitamin K supplementation led to a modest effect on parameters of hip geometry.
PURPOSE
Some clinical studies have suggested that vitamin K prevents bone loss and may improve fracture risk. The aim was to assess whether vitamin K supplementation has an additive effect on bone mineral density (BMD), hip geometry and bone turnover markers (BTMs) in post-menopausal women with osteoporosis (PMO) and sub-optimum vitamin K status receiving bisphosphonate, calcium and/or vitamin D treatment.
METHODS
We conducted a trial in 105 women aged 68.7[12.3] years with PMO and serum vitamin K ≤ 0.4 µg/L. They were randomised to 3 treatment arms; vitamin K (1 mg/day) arm, vitamin K arm (MK-4; 45 mg/day) or placebo for 18 months. They were on oral bisphosphonate and calcium and/or vitamin D. We measured BMD by DXA, hip geometry parameters using hip structural analysis (HSA) software and BTMs. Vitamin K or MK-4 supplementation was each compared to placebo. Intention to treat (ITT) and per protocol (PP) analyses were performed.
RESULTS
Changes in BMD at the total hip, femoral neck and lumbar spine and BTMs; CTX and P1NP did not differ significantly following either K or MK-4 supplementation compared to placebo. Following PP analysis and correction for covariates, there were significant differences in some of the HSA parameters at the intertrochanter (IT) and femoral shaft (FS): IT endocortical diameter (ED) (% change placebo:1.5 [4.1], K arm: -1.02 [5.07], p = 0.04), FS subperiosteal/outer diameter (OD) (placebo: 1.78 [5.3], K arm: 0.46 [2.23] p = 0.04), FS cross sectional area (CSA) (placebo:1.47 [4.09],K arm: -1.02[5.07], p = 0.03).
CONCLUSION
The addition of vitamin K to oral bisphosphonate with calcium and/or vitamin D treatment in PMO has a modest effect on parameters of hip geometry. Further confirmatory studies are needed.
TRIAL REGISTRATION
The study was registered at Clinicaltrial.gov:NCT01232647.
Topics: Female; Humans; Osteoporosis, Postmenopausal; Vitamin K; Diphosphonates; Calcium; Fractures, Bone; Bone Density; Vitamins; Vitamin D; Vitamin K 1; Femur Neck; Calcium, Dietary; Dietary Supplements
PubMed: 37338608
DOI: 10.1007/s11657-023-01288-w -
The Journal of Biological Chemistry 2021Understanding the pathways involved in chlorophyll breakdown provides a molecular map to the color changes observed in plant life on a global scale each fall....
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.
Topics: Arabidopsis; Chlorophyll; Phytol; Plant Leaves
PubMed: 34022219
DOI: 10.1016/j.jbc.2021.100802 -
Critical Reviews in Biotechnology Jun 2015The Vitamin K series, particularly menaquinone, have been attracting research attention, due to the potential in reducing both osteoporosis and cardiovascular diseases.... (Review)
Review
The Vitamin K series, particularly menaquinone, have been attracting research attention, due to the potential in reducing both osteoporosis and cardiovascular diseases. This review provides an overview of the types of vitamin K and their health benefits. This is followed by a critical review of the various biotechnological approaches used in the production of menaquinone, including solid and liquid state fermentations, extraction and recovery. The currently available market information is summarized and future growth prospects are discussed. Recommendations are also given for areas of future research in order to improve the production process for menaquinone and reduce costs.
Topics: Biotechnology; Cardiovascular Diseases; Dietary Supplements; Fermentation; Humans; Osteoporosis; Vitamin K
PubMed: 24044610
DOI: 10.3109/07388551.2013.832142 -
Scientific Reports Aug 2020Wild mushroom foraging involves a high risk of unintentional consumption of poisonous mushrooms which is a serious health concern. This problem arises due to the close...
Wild mushroom foraging involves a high risk of unintentional consumption of poisonous mushrooms which is a serious health concern. This problem arises due to the close morphological resemblances of toxic mushrooms with edible ones. The genus Inocybe comprises both edible and poisonous species and it is therefore important to differentiate them. Knowledge about their chemical nature will unambiguously determine their edibility and aid in an effective treatment in case of poisonings. In the present study, the presence of volatile toxic metabolites was verified in Inocybe virosa by gas chromatography. Methyl palmitate, phenol, 3,5-bis (1,1-dimethyl ethyl) and phytol were the identified compounds with suspected toxicity. The presence of the toxin muscarine was confirmed by liquid chromatography. The in vitro study showed that there was negligible effect of the digestion process on muscarine content or its toxicity. Therefore, the role of muscarine in the toxicity of Inocybe virosa was studied using a bioassay wherein metameters such as hypersalivation, immobility, excessive defecation, heart rate and micturition were measured. Administration of muscarine resulted in an earlier onset of symptoms and the extract showed a slightly stronger muscarinic effect in comparison to an equivalent dose of muscarine estimated in it. Further, the biological fate of muscarine was studied by pharmacokinetics and gamma scintigraphy in New Zealand white rabbits. Significant amount of the toxin was rapidly and effectively concentrated in the thorax and head region. This study closely explains the early muscarinic response such as miosis and salivation in mice. By the end of 24 h, a relatively major proportion of muscarine administered was accumulated in the liver which stands as an explanation to the hepatotoxicity of Inocybe virosa. This is one of the rare studies that has attempted to understand the toxic potential of muscarine which has previously been explored extensively for its pharmaceutical applications.
Topics: Agaricales; Animals; Brain Chemistry; Cell Line; Cell Survival; Female; Gas Chromatography-Mass Spectrometry; Humans; Mice; Muscarine; Palmitates; Phenol; Phytol; Rabbits; Thorax; Toxins, Biological
PubMed: 32792538
DOI: 10.1038/s41598-020-70196-7 -
Biochimica Et Biophysica Acta. Reviews... Mar 2024Several clinical trials and experimental studies have recently shown that vitamin K (VK) supplementation benefits the human body. Specifically, VK participates in... (Review)
Review
Several clinical trials and experimental studies have recently shown that vitamin K (VK) supplementation benefits the human body. Specifically, VK participates in coagulation and is associated with cellular senescence and cancer. VK has a potential anticancer effect in various cancers, such as pancreatic and prostate cancers. Through anti-inflammatory and antioxidant effects, VK can prevent senescence and inhibit cancer metastasis. Therefore, cancer prognosis can be improved by preventing cellular senescence. In addition, VK can inhibit the proliferation, growth, and differentiation of cancer cells through various mechanisms, including induction of c-myc and c-fos genes, regulation of B-cell lymphoma-2 (Bcl-2) and p21 genes, and angiogenesis inhibition. This review aims to discuss the relationship among VK, cellular senescence, and cancer metastasis and thus may improve comprehension of the specific functions of VK in human health. The potential application of VK as an adjuvant therapy for cancer (or in combination with traditional chemotherapy drugs or other vitamins) has also been highlighted.
Topics: Male; Humans; Vitamin K; Neoplasms
PubMed: 38158025
DOI: 10.1016/j.bbcan.2023.189057 -
BMJ Open May 2023Vitamin K has been suggested to have protective effects against progression of vascular calcification and development of cardiovascular disease (CVD). However, few...
Study protocol of the InterVitaminK trial: a Danish population-based randomised double-blinded placebo-controlled trial of the effects of vitamin K (menaquinone-7) supplementation on cardiovascular, metabolic and bone health.
INTRODUCTION
Vitamin K has been suggested to have protective effects against progression of vascular calcification and development of cardiovascular disease (CVD). However, few well-powered randomised controlled trials have examined whether vitamin K prevents progression of vascular calcification in individuals from the general population. The aim of the InterVitaminK trial is to investigate the effects of vitamin K supplementation (menaquinone-7, MK-7) on cardiovascular, metabolic, respiratory and bone health in a general ageing population with detectable vascular calcification.
METHODS AND ANALYSIS
The InterVitaminK trial is a randomised, double-blinded, placebo-controlled, trial. A total of 450 men and women aged 52-82 years with detectable coronary artery calcification (CAC), but without manifest CVD, will be randomised (1:1) to receive daily MK-7 (333 µg/day) or placebo tablets for 3 years. Health examinations are scheduled at baseline, and after 1, 2 and 3 years of intervention. Health examinations include cardiac CT scans, measurements of arterial stiffness, blood pressure, lung function, physical function, muscle strength, anthropometric measures, questionnaires on general health and dietary intake, and blood and urine sampling. The primary outcome is progression of CAC from baseline to 3-year follow-up. The trial has 89% power to detect a between-group difference of at least 15%. Secondary outcomes are bone mineral density, pulmonary function and biomarkers of insulin resistance.
ETHICS AND DISSEMINATION
Oral MK-7 supplementation is considered safe and has not been found to cause severe adverse events. The Ethical Committee of the Capital Region (H-21033114) approved the protocol. Written informed consent is obtained from all participants and the trial is conducted in accordance with the Declaration of Helsinki II. Both negative and positive findings will be reported.
TRIAL REGISTRATION NUMBER
NCT05259046.
Topics: Male; Humans; Female; Vitamin K; Bone Density; Vitamin K 2; Lung; Coronary Artery Disease; Vascular Calcification; Dietary Supplements; Denmark; Double-Blind Method; Randomized Controlled Trials as Topic
PubMed: 37208133
DOI: 10.1136/bmjopen-2023-071885 -
Journal of Thrombosis and Haemostasis :... Sep 2022Vitamin K antagonists (VKAs), such as warfarin, are oral anticoagulants widely used to treat and prevent thromboembolic diseases. Therapeutic use of these drugs requires... (Review)
Review
Vitamin K antagonists (VKAs), such as warfarin, are oral anticoagulants widely used to treat and prevent thromboembolic diseases. Therapeutic use of these drugs requires frequent monitoring and dose adjustments, whereas overdose often causes severe bleeding. Addressing these drawbacks requires mechanistic understandings at cellular and structural levels. As the target of VKAs, vitamin K epoxide reductase (VKOR) generates the active, hydroquinone form of vitamin K, which in turn drives the γ-carboxylation of several coagulation factors required for their activity. Crystal structures revealed that VKAs inhibit VKOR via mimicking its catalytic process. At the active site, two strong hydrogen bonds that facilitate the catalysis also afford the binding specificity for VKAs. Binding of VKAs induces a global change from open to closed conformation. Similar conformational change is induced by substrate binding to promote an electron transfer process that reduces the VKOR active site. In the cellular environment, reducing partner proteins or small reducing molecules may afford electrons to maintain the VKOR activity. The catalysis and VKA inhibition require VKOR in different cellular redox states, explaining the complex kinetics behavior of VKAs. Recent studies also revealed the mechanisms underlying warfarin resistance, warfarin dose variation, and antidoting by vitamin K. These mechanistic understandings may lead to improved anticoagulation strategies targeting the vitamin K cycle.
Topics: Anticoagulants; Catalytic Domain; Fibrinolytic Agents; Humans; Vitamin K; Vitamin K 1; Vitamin K Epoxide Reductases; Warfarin
PubMed: 35748323
DOI: 10.1111/jth.15800 -
Current Opinion in Structural Biology Dec 2020Menaquinones (vitamin K2) are a family of redox-active small molecules with critical functions across all domains of life, including energy generation in bacteria and... (Review)
Review
Menaquinones (vitamin K2) are a family of redox-active small molecules with critical functions across all domains of life, including energy generation in bacteria and bone health in humans. The enzymes involved in menaquinone biosynthesis also have bioengineering applications and are potential antimicrobial drug targets. New insights into the essential roles of menaquinones, and their potential to cause redox-related toxicity, have highlighted the need for this pathway to be tightly controlled. Here, we provide an overview of our current understanding of the classical menaquinone biosynthesis pathway in bacteria. We also review recent discoveries on protein-level allostery and sublocalisation of membrane-bound enzymes that have provided insight into the regulation of flux through this biosynthetic pathway.
Topics: Allosteric Regulation; Bacteria; Vitamin K 2
PubMed: 32634692
DOI: 10.1016/j.sbi.2020.05.005