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Screening of selected alkaloids of Fumariaceae and Amaryllidaceae families on Farnesoid X receptor and the G protein-coupled bile acid receptor 1
Hutníková, Miriama ; Pávek, Petr (advisor) ; Chlebek, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Miriama Hutníková Supervisor: Prof. PharmDr. Petr Pávek, PhD. Title of diploma thesis: Screening of selected alkaloids of Fumariaceae and Amaryllidaceae families on the farnesoid X receptor and the G protein coupled receptor 1 Farnesoid X receptor (FXR) and bile acid receptor associated with G protein 1 (TGR5) significantly affect metabolic processes in the human body. The role of FXR in neuronal apoptosis in Alzheimer's disease (AD) has also been discovered. The possible structural similarity of the small lipophilic molecules binding to these receptors and the alkaloids found in the plants Corydalis cava and Narcissus pseudonarcissus, as well as the richoften use of these plants in traditional medicine, represent a potential therapeutic intervention for these molecules. In our screening methods, we performed tests using a luciferase gene reporter assay to determine the ability of the alkaloids to interact with FXR and TGR5 in the HepG2 cell line. Many derivatives have shown a strong ability to antagonize FXR and TGR5 activated by obethicholic (OCA) or litocholic (LCA) acids in this assay. Some of the compounds also demonstrated the ability to potentiate the effects of OCA or LCA. Cytotoxicity...
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Screening of selected alkaloids of Fumariaceae and Amaryllidaceae families on Farnesoid X receptor and the G protein-coupled bile acid receptor 1
Hutníková, Miriama ; Pávek, Petr (advisor) ; Chlebek, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Miriama Hutníková Supervisor: Prof. PharmDr. Petr Pávek, PhD. Title of diploma thesis: Screening of selected alkaloids of Fumariaceae and Amaryllidaceae families on the farnesoid X receptor and the G protein coupled receptor 1 Farnesoid X receptor (FXR) and bile acid receptor associated with G protein 1 (TGR5) significantly affect metabolic processes in the human body. The role of FXR in neuronal apoptosis in Alzheimer's disease (AD) has also been discovered. The possible structural similarity of the small lipophilic molecules binding to these receptors and the alkaloids found in the plants Corydalis cava and Narcissus pseudonarcissus, as well as the richoften use of these plants in traditional medicine, represent a potential therapeutic intervention for these molecules. In our screening methods, we performed tests using a luciferase gene reporter assay to determine the ability of the alkaloids to interact with FXR and TGR5 in the HepG2 cell line. Many derivatives have shown a strong ability to antagonize FXR and TGR5 activated by obethicholic (OCA) or litocholic (LCA) acids in this assay. Some of the compounds also demonstrated the ability to potentiate the effects of OCA or LCA. Cytotoxicity...
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Interaction of PPARG gene polymorphisms with diet components in pathogenesis of type 2 diabetes
Petrů, Karolína ; Šeda, Ondřej (advisor) ; Schierová, Michaela (referee)
Type 2 diabetes is a multifactorial trait as interactions between genetic predispositions and environmental factors contribute to its pathogenesis. Nuclear receptor PPARG (peroxisome proliferator-activated receptor gamma) belongs among genes with substantial impact on pathophysiological processes leading to manifestation of type 2 diabetes. Metaanalyses of human studies showed that several common polymorphisms of this gene are involved in interactions with environmental factors, particularly diet, physical activity and medication. The aim of this Bachelor thesis is to summarize current knowledge on nutrigenetic interactions comprising polymorphisms of PPARG gene and specific qualitative and quantitative parameters of the diet in relation to pathogenesis of type 2 diabetes.
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