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Influence of natural polyphenolic substances on p53 protein expression
Bušanski, Patrik ; Němcová, Andrea (referee) ; Brázda, Václav (advisor)
The tumor suppressor protein p53 is one of the major regulators of the cell cycle after DNA damage. In addition to stopping the cycle and repairing DNA, it can, in extreme cases, induce programmed cell death - apoptosis. Mutations in the gene encoding p53 are present in more than 50% of cancer cases. This thesis examines alternative natural polyphenolic substances that could increase the level and expression of p53 protein in tumor cells. These substances could be an alternative to non-specific cytostatics, which bring many undesirable additional effects during treatment. In the theoretical part of the thesis the structure and properties of the p53 protein and describes alternative therapeutic approaches with a focus on polyphenolic substances is explained. The aim of the experimental part was to determine the effect of curcumin and resveratrol in comparison with often used cytostatic drug, doxorubicin, on cell viability of tumor cells and on p53 protein levels. The effect of these substances on the binding of p53 to DNA in yeast systems was also examined. It was found that doxorubin efficiency is many times higher than the examined polyphenolic agents, but resveratrol was showing some potential as a suitable alternative in the treatment of tumors, thanks to the ability to activate apotosis. It was clearly demonstrated that there is an association between induced programmed death and increased p53 protein expression after resveratrol treatment.
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Design and Synthesis of Hybrid Compounds Based on Tacrin/Resveratrol Derivatives
Jeřábek, Jakub ; Doležal, Martin (advisor) ; Miletín, Miroslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Student: Jakub Jeřábek Supervisors: Prof. PharmDr. Martin Doležal, Ph.D. Prof. Maria Laura Bolognesi Title of Thesis: Design and Synthesis of Hybrid Compounds Based on Tacrine/Resveratrol Derivatives Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder, in which a progressive dementia appears. The cause of AD is currently unknown, however, scientific research has revealed several pathological hallmarks - β-amyloid plaques and neurofibrillary tangles. These changes cause gradual disintegration of nerve cells and they change the metabolism in the brain. The current drugs are not able to treat the cause of the disease, being able only to delay the onset of severe symptoms. The basic drugs for AD treatment are acetylcholinesterase (AChE, E.C. 3.1.1.7) inhibitors and, more recently approved, N-methyl- D-aspartate (NMDA) receptor antagonist memantine. These drugs are able to increase cholinergic activity or preventing glutamate excitotoxicity in the patient's brain, thus improving cognitive functions and delaying severe stages of the disease. One of the emerging approaches in drug synthesis represents multi-target-directed ligands (MTDLs). Apart from the ability...
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Výskyt a význam fenolových sloučenin v potravinách
Hvězdová, Kristýna
This Bachelor thesis I wrote in the years 2015/2016 at Mendel University in Brno Faculty of Horticulture at Department of Post-Harvest Technology of Horticulture Products. The work contains division and definition of phenolic compounds in foodstuff and their characteristics chemical reaction of phenolic compounds. Qualitative and quantitative agency phenolic compounds in chosen foodstuff, resveratrol in wine and athokyans in plants product, is describe in my own comments. The comments also includes assessment occurrence and leverage of phenolic compounds on human health.
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Stanovení přírodních antioxidantů v ovocných džusech
Pelcová, Lucie
The objective of this thesis was to investigate the content of polyphenols in these juices: apple from concentrate, apple produced by direct compression, orange with pulp, orange without pulp, grapefruit from concentrate, juice from red grapes, pomegranate and purple carrots. The measurement was taken by high performance liquid chromatography and mass spectrometry. The polyphenol with the highest overall value and also the most important of polyphenols in citrus juices was hesperidin. Significant content of cryptochlorogenic acid and hyperoside was in apple juice. Apple juice produced by direct compression also contained a lot of catechin. Epigallocatechin, epicatechin and gallic acid were substances with the highest value measured in the juice of the pomegranate. Catechin, epicatechin and epigallocatechin were most prevalent in the grape juice. Quantitatively the most important compounds of juice from purple carrots were caffeic and cryptochlorogenic acid.
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Design and Synthesis of Hybrid Compounds Based on Tacrin/Resveratrol Derivatives
Jeřábek, Jakub ; Doležal, Martin (advisor) ; Miletín, Miroslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Student: Jakub Jeřábek Supervisors: Prof. PharmDr. Martin Doležal, Ph.D. Prof. Maria Laura Bolognesi Title of Thesis: Design and Synthesis of Hybrid Compounds Based on Tacrine/Resveratrol Derivatives Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder, in which a progressive dementia appears. The cause of AD is currently unknown, however, scientific research has revealed several pathological hallmarks - β-amyloid plaques and neurofibrillary tangles. These changes cause gradual disintegration of nerve cells and they change the metabolism in the brain. The current drugs are not able to treat the cause of the disease, being able only to delay the onset of severe symptoms. The basic drugs for AD treatment are acetylcholinesterase (AChE, E.C. 3.1.1.7) inhibitors and, more recently approved, N-methyl- D-aspartate (NMDA) receptor antagonist memantine. These drugs are able to increase cholinergic activity or preventing glutamate excitotoxicity in the patient's brain, thus improving cognitive functions and delaying severe stages of the disease. One of the emerging approaches in drug synthesis represents multi-target-directed ligands (MTDLs). Apart from the ability...
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Influence of resveratrol on bile flow.
Paclíková, Kristýna ; Doleželová, Eva (advisor) ; Cermanová, Jolana (referee)
Kristýna Paclíková Influence of resveratrol on bile flow Diploma thesis Charles University in Prague, Faculty of Pharmacy in Hradec Králové Pharmacy Background: Protective effect of resveratrol is shown in many experimental models of cholestasis, but its effect on bile production in healthy individuals has not been studied yet. As the use of resveratrol is frequent in population, the aim of this thesis was to investigate the effect of resveratrol on the bile flow in healthy animals and the clarification of the mechanism of this effect. Methods: Wistar rats (n = 6, in each group, weighing 280 to 320 g) were divided into two groups: control group (Control) and the group of rats administered with resveratrol (10mg/kg/day, p.o.) for 28 days (RES). In vivo clearance study was performed to analyze bile production. Analysis of mRNA and protein expression of the transport proteins was performed by qRT-PCR and Western blot. Results: Resveratrol led to a significant increase in the cumulative bile flow. Analysis of mRNA and protein expression of the transport proteins revealed that bile flow is changed due to posttranscriptional induction of canalicular transporters Bsep and Mrp2. Simultaneously, resveratrol led to induction of Mrp4 efflux protein, expressed at the basolateral membrane of hepatocytes....
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Resveratrol - effects on biological age
Pokorná, Zuzana ; Klemera, Petr (advisor) ; Kuchařová, Monika (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of biophysics and physical chemistry Candidate: Zuzana Pokorná Supervisor: Doc. RNDr. Petr Klemera, CSc. Title of diploma thesis: Resveratrol - effect on the biological age Objective: Resveratrol is a natural polyphenol contained in number of plants. It is a potent antioxidant, which is known to have a number of beneficial health effects and be part of many biological processes. The compound is produced by plants to increase their survival and resistance to disease. We found the effect of Resveratrol on parameters of biological age-on the threshold of perception of the intensity of the volume (hearing) and reaction rate. Methods : A group of people used the resveratrol in a dose of 170 mg per day for 40 days. We measured by the PC program the selected parameter of hearing and reaction rate. Results : It has been shown that statistically significant improvement of hearing has occurred. The exact mechanism of the effect is not known. Probably operates through a group of enzymes, sirtuins. Reaction rate was not affected by substance. Conclusions : We have reviewed the potential effect of Resveratrol on human biological age. The improvement of hearing has been shown at the 0,01 significance level. The biggest improvement was...
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The effect of silymarin, naringin and resveratrol on the liver damage induced by some xenobiotics
Kovaříková, Pavla ; Eybl, Vladislav (advisor) ; Anzenbacherová, Eva (referee) ; Mayer, Otto (referee)
The vast majority of exogenous substances is metabolized in the liver. In the course of the biotransformation, partly biologically non-active products, partly reactive species leading to cell structure injury and even to the liver failure are produced. Oxidative stress plays a significant role in the toxic- and drug-induced liver damage. Endogenous and exogenous antioxidants contribute to equilibrium between the production and the elimination of reactive oxygen species and thus prevent the oxidative stress. In acute experiments in rats we examined the ability of natural antioxidants silymarin, naringin and resveratrol and of synthetic chelator deferipron to protect against liver damage induced by paracetamol, thioacetamide and tamoxifen. The following parameters of oxidative stress were measured in the liver homogenates: level of lipid peroxidation (LP), concentration of reduced glutathione (GSH), activities of glutathione peroxidase (GPx) and of catalase (CAT); in some cases the iron liver content. The following markers of liver damage were measured in serum: alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH). Concernig markers of oxidative status, silymarin exerted the most efficient antioxidant properties amelioratig the TAA- and TAM-induced lipid...
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Contribution to the use of new types of carbon paste and fiber electrodes for voltammetric and amperometric determination of 5-amino-6-nitroquinoline and resveratrol
Němcová, Lenka ; Zima, Jiří (advisor) ; Vytřas, Karel (referee) ; Navrátil, Tomáš (referee)
7 ABSTRACT (EN) This dissertation thesis is focused on the study of electrochemical properties of new types of carbon paste electrodes (CPE) and carbon fiber rod electrodes (CFRE), which were used for the development of new highly sensitive and selective voltammetric and amperometric methods for the determination of 5-amino-6-nitroquinoline and trans- and cis- isomers of resveratrol. The carbon paste electrodes were compared in terms of size of the microparticles of glassy carbon contained in the paste (diameters 0.4 - 12 µm; 10 - 20 µm; 20 - 50 µm) in comparison with carbon paste electrode consisting of crystalline graphite and solid glassy carbon electrode. The electrochemical properties were tested using potassium hexacyanoferrate in an aqueous supporting electrolyte and 5-amino-6-nitroquinoline (5A6NQ) in a mixed methanol-water supporting electrolyte. The carbon paste electrode was further used in an amperometric detector of a wall-jet type connected in series with a spectrophotometric detector for the development of a new HPLC method with electrochemical detection and spectrophotometric detection for the determination of trans-resveratrol and cis-resveratrol in samples of grains, hulls and leaves of common and tartary buckwheat. The method was optimized and used for the determination of resveratrol in...
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Vliv požívání vína na lidský organismus
Blažková, Kateřina
You have got into your hands a bachelor thesis about impact of usage wine to the human organism. It is focused how wine consumption is influencing the human health, mainly what are effects of alcohol contained in the wine. The first part summarizes the general findings about the wine and what all substances are located in and briefly describing production and distinguishing of wine. I deal here wine history, the usage of wine for medicine and legislative purposes. In the second half of the thesis contain information obtained from collected sources, what include articles, scientist studies and researches dealing with this problematic. There is information about heart diseases, cancer and other diseases that may have a connection to using of wine. Mentioned are also the French paradox and the effects of discussed substance to Resveratrol.
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