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Journal of Advanced Pharmaceutical... 2024Leaves of have medicinal potential which has gained attention from researchers around the world. This study has an objective to screen the antioxidant and cytotoxicity...
Leaves of have medicinal potential which has gained attention from researchers around the world. This study has an objective to screen the antioxidant and cytotoxicity of ethyl acetate extract from leaves and its fraction. The fine powder of was macerated in methanol and further partitioned using two different solvents, namely n-hexane and ethyl acetate. In this article, we reported the screening results for ethyl acetate extract. Fractionation was then performed on the extract by means of column chromatography by gradient elution resulting in five combined fractions. Brine shrimp lethality test and 1-diphenyl-2-pycrilhidrazil (DPPH) assays were employed to evaluate the cytotoxicity and antioxidant of the extract, respectively. Characterization using gas chromatography-mass spectroscopy (GC-MS) was then conducted. The cytotoxicity of the samples was indicated by median lethal concentration values ranging from 28.84 to 1023.3 ppm. As for the antioxidant activity, the DPPH median inhibitory concentration values ranged from 4.12 to 180.66 ppm. GC-MS analysis on the most bioactive fraction revealed the predominating phytochemical contents of neophytadiene, palmitic acid, and phytol. In conclusion, the fraction of ethyl acetate extract from leaves could potentially act as a strong antioxidant and moderate cytotoxic agent.
PubMed: 38903553
DOI: 10.4103/JAPTR.JAPTR_470_23 -
Cells Jun 2024Authors have demonstrated that apoptosis activation is a pathway related to cartilage degradation characteristics of the OA process. Autophagy is an adaptive response to...
Authors have demonstrated that apoptosis activation is a pathway related to cartilage degradation characteristics of the OA process. Autophagy is an adaptive response to protect cells from various environmental changes, and defects in autophagy are linked to cell death. In this sense, decreased autophagy of chondrocytes has been observed in OA articular cartilage. The aim of this work was to study the role of OA mitochondria in apoptosis, autophagy, and senescence, using OA and Normal (N) transmitochondrial cybrids. Results: OA cybrids incubated with menadione showed a higher percentage of late apoptosis and necrosis than N cybrids. Stimulation of cybrids with staurosporine and IL-1β showed that OA cybrids were more susceptible to undergoing apoptosis than N cybrids. An analysis of the antioxidant response using menadione on gene expression revealed a lower expression of nuclear factor erythroid 2-like 2 and superoxide dismutase 2 in OA than N cybrids. Activation of microtubule-associated protein 1A/1B-light chain 3 was reduced in OA compared to N cybrids. However, the percentage of senescent cells was higher in OA than N cybrids. Conclusion: This work suggests that mitochondria from OA patients could be involved in the apoptosis, autophagy, and senescence of chondrocytes described in OA cartilage.
Topics: Autophagy; Humans; Osteoarthritis; Apoptosis; Cellular Senescence; Mitochondria; Chondrocytes; Microtubule-Associated Proteins; NF-E2-Related Factor 2; Superoxide Dismutase; Aged; Interleukin-1beta; Male; Middle Aged; Vitamin K 3; Female
PubMed: 38891108
DOI: 10.3390/cells13110976 -
Foods (Basel, Switzerland) May 2024This study aimed to investigate the efficacy of supercritical CO (SC-CO) extraction in enhancing the extraction rate, purity, and antioxidant activity of (Keng) McClure...
This study aimed to investigate the efficacy of supercritical CO (SC-CO) extraction in enhancing the extraction rate, purity, and antioxidant activity of (Keng) McClure (Poaceae) leaf terpenoids (ILLTs). Crude extracts obtained from leaves were subjected to qualitative and quantitative analyses, revealing neophytadiene, phytol, β-sitosterol, β-amyrone, squalene, and friedelin as the primary terpenoid constituents, identified through gas chromatography-mass spectrometry (GC-MS). Compared with steam distillation extraction (SD), simultaneous distillation extraction (SDE), ultra-high pressure-assisted n-hexane extraction (UHPE-Hex), ultra-high pressure-assisted ethanol extraction (UHPE-EtOH), ultrasound-assisted n-hexane extraction (UE-Hex), and ultrasound-assisted ethanol extraction (UE-EtOH), SC-CO exhibited a superior ILLT extraction rate, purity, and antioxidant activity. Scanning electron microscopy (SEM) observations of the residues further revealed more severe damage to both the residues and their cell walls after SC-CO extraction. Under optimal parameters (4.5 h, 26 MPa, 39 °C, and 20% ethyl alcohol), the ILLT extraction rate with SC-CO reached 1.44 ± 0.12 mg/g, which was significantly higher than the rates obtained by the other six methods. The subsequent separation and purification using WelFlash C18-l, BUCHI-C18, and Sephadex LH-20 led to an increase in the purity of the six terpenoid components from 12.91% to 93.34%. Furthermore, the ILLTs demonstrated cytotoxicity against HepG2 cells with an IC value of 148.93 ± 9.93 μg/mL. Additionally, with increasing concentrations, the ILLTs exhibited an enhanced cellular antioxidant status, as evidenced by reductions in both reactive oxygen species (ROS) and malondialdehyde (MDA) levels.
PubMed: 38890947
DOI: 10.3390/foods13111719 -
Poultry Science Jul 2024Sodium dehydroacetate (DHA-Na) is a fungicidal preservative widely used in food and animal feed. DHA-Na can induce coagulation disorders in rats and poultry by...
Sodium dehydroacetate (DHA-Na) is a fungicidal preservative widely used in food and animal feed. DHA-Na can induce coagulation disorders in rats and poultry by inhibiting carboxylation of vitamin K-dependent proteins; it can also impair bone development in zebrafish. However, the effects of DHA-Na on broiler chicken bones remain unknown. Here, we assessed whether DHA-Na impairs bone development in broiler chickens. We administered Suji yellow chickens with 200 to 800 mg/kg DHA-Na, 2 mg/kg vitamin K, or both for 2 mo. Bone metabolite-related serum indicators, tissue micromorphology, and relevant protein expression were monitored during the treatment period. We also assessed primary chicken osteoblast activity, differentiation, and bone metabolite-related proteins after treatment with DHA-Na, vitamin K, or both. The results demonstrated that DHA-Na reduced bone index values and serum and bone osteoblast differentiation marker levels but blocked bone vitamin K cycle. DHA-Na also increased serum osteoclast differentiation marker levels, as well as the bone ratio of receptor activator of nuclear factor kappa-Β ligand to osteoprotegerin ratio. Moreover, DHA-Na reduced bone trabecular number, thickness, and area and increased trabecular separation considerably. In general, compared with the control group, the DHA-Na group demonstrated impairments in osteoblast activity and differentiation, as well as in the vitamin K cycle. By contrast, vitamin K supplementation led to considerable attenuation of the DHA-Na-induced decrease in osteogenic marker levels, along with a considerable increase in serum bone absorption marker levels and restoration of DHA-Na-induced bone microstructure damage. Vitamin K also attenuated DHA-Na-induced impairment in osteoclasts. In conclusion, the results indicated that in broiler chickens, DHA-Na supplementation can damage bones by inhibiting osteoblast function and increasing osteoclast activity; this damage can be prevented through vitamin K supplementation.
Topics: Animals; Chickens; Osteoblasts; Bone and Bones; Animal Feed; Dietary Supplements; Vitamin K; Diet; Fungicides, Industrial; Male; Dose-Response Relationship, Drug; Bone Development; Pyrones
PubMed: 38805999
DOI: 10.1016/j.psj.2024.103834 -
The New Phytologist Jul 2024Understanding the genetic basis of how plants defend against pathogens is important to monitor and maintain resilient tree populations. Swiss needle cast (SNC) and...
Understanding the genetic basis of how plants defend against pathogens is important to monitor and maintain resilient tree populations. Swiss needle cast (SNC) and Rhabdocline needle cast (RNC) epidemics are responsible for major damage of forest ecosystems in North America. Here we investigate the genetic architecture of tolerance and resistance to needle cast diseases in Douglas-fir (Pseudotsuga menziesii) caused by two fungal pathogens: SNC caused by Nothophaeocryptopus gaeumannii, and RNC caused by Rhabdocline pseudotsugae. We performed case-control genome-wide association analyses and found disease resistance and tolerance in Douglas-fir to be polygenic and under strong selection. We show that stomatal regulation as well as ethylene and jasmonic acid pathways are important for resisting SNC infection, and secondary metabolite pathways play a role in tolerating SNC once the plant is infected. We identify a major transcriptional regulator of plant defense, ERF1, as the top candidate for RNC resistance. Our findings shed light on the highly polygenic architectures underlying fungal disease resistance and tolerance and have important implications for forestry and conservation as the climate changes.
Topics: Disease Resistance; Plant Diseases; Pseudotsuga; Genome-Wide Association Study; Ascomycota; Trees; Adaptation, Physiological; Multifactorial Inheritance; Gene Expression Regulation, Plant; Genes, Plant
PubMed: 38803110
DOI: 10.1111/nph.19797 -
Revista Medica de Chile Jun 2023Human intoxication by long-acting anticoagulant rodenticides, known as superwarfarins, causes coagulopathy that is difficult to manage. We present the case of a...
Human intoxication by long-acting anticoagulant rodenticides, known as superwarfarins, causes coagulopathy that is difficult to manage. We present the case of a 42-year-old man who ingested a toxic dose of rodenticide in a suicide attempt, evolving with epistaxis, INR of 11.6, and needing hospitalization. For seven days, serial controls of coagulation tests were carried out, with optimization of different doses of Vitamin K supplementation. The case highlights this type of anticoagulant's potency and prolonged half-life (approximately six weeks), which requires regular clinical control and satisfactory treatment adherence.
Topics: Humans; Male; Adult; Rodenticides; Suicide, Attempted; Anticoagulants; 4-Hydroxycoumarins; Vitamin K
PubMed: 38801389
DOI: 10.4067/s0034-98872023000600797 -
Therapeutic Advances in Cardiovascular... 2024Atrial fibrillation (AF) accounts for 40% of all cardiac arrhythmias and is associated with a high risk of stroke and systemic thromboembolic complications. Dabigatran,... (Review)
Review
Atrial fibrillation (AF) accounts for 40% of all cardiac arrhythmias and is associated with a high risk of stroke and systemic thromboembolic complications. Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that have been proven to prevent stroke in patients with non-valvular AF. This review summarizes the pharmacokinetics, pharmacodynamics, and drug interactions of DOACs, as well as new data from pharmacogenetic studies of these drugs. This review is aimed at analyzing the scientific literature on the gene polymorphisms involved in the metabolism of DOACs. We searched PubMed, Cochrane, Google Scholar, and CyberLeninka (Russian version) databases with keywords: 'dabigatran', 'apixaban', 'rivaroxaban', 'edoxaban', 'gene polymorphism', 'pharmacogenetics', '', '', '', '', and ''. The articles referred for this review include (1) full-text articles; (2) study design with meta-analysis, an observational study in patients taking DOAC; and (3) data on the single-nucleotide polymorphisms and kinetic parameters of DOACs (plasma concentration), or a particular clinical outcome, published in English and Russian languages during the last 10 years. The ages of the patients ranged from 18 to 75 years. Out of 114 reviewed works, 24 were found eligible. As per the available pharmacogenomic data, polymorphisms affecting DOACs are different. This may aid in developing individual approaches to optimize DOAC pharmacotherapy to reduce the risk of hemorrhagic complications. However, large-scale population studies are required to determine the dosage of the new oral anticoagulants based on genotyping. Information on the genetic effects is limited owing to the lack of large-scale studies. Uncovering the mechanisms of the genetic basis of sensitivity to DOACs helps in developing personalized therapy based on patient-specific genetic variants and improves the efficacy and safety of DOACs in the general population.
Topics: Humans; Atrial Fibrillation; Administration, Oral; Hemorrhage; Pharmacogenomic Variants; Risk Factors; Anticoagulants; Treatment Outcome; Stroke; Risk Assessment; Phenotype; Polymorphism, Single Nucleotide; Vitamin K; Drug Interactions
PubMed: 38801157
DOI: 10.1177/17539447241249886 -
Narra J Apr 2024Fatigue, a condition of lack of energy and motivation resulting in the feeling of extreme tiredness or exhaustion, is usually prevented and treated with ergogenic aids,...
Fatigue, a condition of lack of energy and motivation resulting in the feeling of extreme tiredness or exhaustion, is usually prevented and treated with ergogenic aids, such as in the form of nutritional supplements. Papaya ( may be a potential candidate for ergogenic aids, considering its healthy secondary metabolite properties and number of metabolite compounds that could be affected by the location where the plant growing. The aim of this study was to identify the phytochemicals of papaya leaves from three different locations: geothermal, coastal, and urban areas in Aceh province, Indonesia. Concentrations of papaya leaf with the highest number of secondary metabolite compounds were tested in rats to measure blood lactate acid concentrations after strenuous exercise. The number of chemical compounds identified from the three locations was 24 compounds; 23 compounds and 17 compounds, respectively. The highest concentration of chemical compounds that have antifatigue activity contained in all papaya leaf samples were neophytadiene, linolenic acid, gamma tocopherol, hexadecanoic acid, vitamin E, carpaine, octadecatrienoic acid, nor lean-12-ene, squalene, and phytol. Furthermore, most of the compounds' highest concentrations were found in papaya leaves from the coastal area and, therefore, tested on the animal model. Treatment was provided in 12 male rats with different doses of papaya powder supplements for 15 days. The results showed that lactic acid levels of rats received a dose of 400 mg/kg of papaya leaf extract reduced the lactic acid concentration (=0.014) compared with the control group. This study highlights that papaya leaves from the coastal area have the most potential activities as ergogenic herbal aid and were able to reduce lactic acid levels in rats after strenuous exercise.
Topics: Animals; Carica; Indonesia; Rats; Plant Leaves; Plant Extracts; Male; Fatigue; Phytochemicals; Lactic Acid
PubMed: 38798837
DOI: 10.52225/narra.v4i1.321 -
Cells May 2024The TAM receptor ligand Gas6 is known for regulating inflammatory and immune pathways in various organs including the brain. Gas6 becomes fully functional through the...
The TAM receptor ligand Gas6 is known for regulating inflammatory and immune pathways in various organs including the brain. Gas6 becomes fully functional through the post-translational modification of multiple glutamic acid residues into γ-carboxyglutamic in a vitamin K-dependent manner. However, the significance of this mechanism in the brain is not known. We report here the endogenous expression of multiple components of the vitamin K cycle within the mouse brain at various ages as well as in distinct brain glial cells. The brain expression of all genes was increased in the postnatal ages, mirroring their profiles in the liver. In microglia, the proinflammatory agent lipopolysaccharide caused the downregulation of all key vitamin K cycle genes. A secreted Gas6 protein was detected in the medium of both mouse cerebellar slices and brain glial cell cultures. Furthermore, the endogenous Gas6 γ-carboxylation level was abolished through incubation with the vitamin K antagonist warfarin and could be restored through co-incubation with vitamin K1. Finally, the γ-carboxylation level of the Gas6 protein within the brains of warfarin-treated rats was found to be significantly reduced ex vivo compared to the control brains. In conclusion, we demonstrated for the first time the existence of a functional vitamin K cycle within rodent brains, which regulates the functional modification of endogenous brain Gas6. These results indicate that vitamin K is an important nutrient for the brain. Furthermore, the measurement of vitamin K-dependent Gas6 functionality could be an indicator of homeostatic or disease mechanisms in the brain, such as in neurological disorders where Gas6/TAM signalling is impaired.
Topics: Animals; Intercellular Signaling Peptides and Proteins; Vitamin K; Brain; Mice; Mice, Inbred C57BL; Rats; Male; Warfarin; Microglia; Lipopolysaccharides; Neuroglia
PubMed: 38786095
DOI: 10.3390/cells13100873 -
The New Phytologist Jul 2024Investigating plant responses to climate change is key to develop suitable adaptation strategies. However, whether changes in land management can alleviate increasing...
Investigating plant responses to climate change is key to develop suitable adaptation strategies. However, whether changes in land management can alleviate increasing drought threats to crops in the future is still unclear. We conducted a management × drought experiment with winter wheat (Triticum aestivum L.) to study plant water and vegetative traits in response to drought and management (conventional vs organic farming, with intensive vs conservation tillage). Water traits (root water uptake pattern, stem metaxylem area, leaf water potential, stomatal conductance) and vegetative traits (plant height, leaf area, leaf Chl content) were considered simultaneously to characterise the variability of multiple traits in a trait space, using principal component analysis. Management could not alleviate the drought impacts on plant water traits as it mainly affected vegetative traits, with yields ultimately being affected by both management and drought. Trait spaces were clearly separated between organic and conventional management as well as between drought and control conditions. Moreover, changes in trait space triggered by management and drought were independent from each other. Neither organic management nor conservation tillage eased drought impacts on winter wheat. Thus, our study raised concerns about the effectiveness of these management options as adaptation strategies to climate change.
Topics: Triticum; Droughts; Water; Seasons; Quantitative Trait, Heritable; Principal Component Analysis; Plant Leaves; Agriculture; Plant Roots
PubMed: 38785184
DOI: 10.1111/nph.19851