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Bile Acids and Their Derivatives – the Promising Therapeutic Remedies

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Bile acids are important physiological agents with essential role in solubilizing fats for absorption in the small intestine. Enterohepatic circulation of bile acids that is regulated by a complex membrane transport system in the liver and intestine plays a central role in nutrient absorption and ...

Bile acids are important physiological agents with essential role in solubilizing fats for absorption in the small intestine. Enterohepatic circulation of bile acids that is regulated by a complex membrane transport system in the liver and intestine plays a central role in nutrient absorption and distribution, metabolic regulation and homeostasis. Metabolism of bile acids is brought solely by the gut microflora, with both the composition of bile acids and the gut microflora found to be disturbed in various diseases such as inflammatory bowel diseases, nonalcoholic fatty liver disease, diabetes and obesity. Bile acids have been used as the standard treatment for gallstones and cholestatic liver disease since early 1970s but today their therapeutic role is expanding. Therapeutic potential of bile acids and their derivatives as metabolic regulators with antihyperglycemic and antihyperlypemic effects is now well recognized opening up new avenues in pharmacotherapy of diabetes, obesity and other ‘diseases of civilization’.

It is also known that bile acids act as endocrine signaling molecules that activate nuclear and membrane receptors controlling integrative metabolism and energy balance. In addition, several intracellular signal transduction cascades modify the expression of a great number of target genes relevant for bile acid, cholesterol, lipid and carbohydrate metabolism, as well as genes involved in inflammation, fibrosis and carcinogenesis. Regulation of gene transcription is frequently modified by epigenetic changes, mediated by environmental factors like nutrients, gut microbiota or drugs. The activity of bile acid-activated receptors may be repressed or amplified by epigenetic modifications. Epigenetics is now appreciated as one of the most promising areas for development of potential therapies for treatment of human diseases, including metabolic diseases. Understanding the epigenetic regulation of metabolic integration and endocrine signaling exerted by bile acids, may further contribute to development of new strategies for treatment of deregulated metabolism and cellular homeostasis.

The specific structure and amphipathic nature of bile acids play essential role in enhancing the absorption of poorly permeable drug molecule by altering the intestinal membrane permeability. This property makes them useful in the development of drugs as pharmaceutical tools and potential drug carrier systems that could improve, control and localize drug absorption and delivery.

Besides, the incorporation of a certain amount of exogenous bile acids, which are highly susceptible to digestion effect of intestinal bile acids, into the lipid-based nanovesicles like liposomes, niosomes, pharmacosomes, ethosomes, sphinosomes, herbosomes, cubosomes and colloidosomes, showed a significant resistance against the destructive attack of the intestinal bile acids. Thereby, inclusion of specific type and content amount of exogenous bile acids and its conjugate into the lipid-based nanovesicle formulations can stabilize the lipid-bilayer membranes against the further detergent effects of intestinal bile acids. However, a further understanding of the colloidal and interfacial mechanisms underlying the role of bile acid in the partitioning, transport and uptake processes is a key that will lead to promising strategies on improving the physical stability of lipid-based nanoparticles for oral drug delivery system.

The overall goal of this Research Topic is to revisit the role of bile acid in the treatment of different diseases and technology of new pharmaceutical formulations and products, with a focus on pharmacokinetics and the mechanisms of action- looking for the papers which will fill the gap of knowledge on bile acids.


Keywords: Bile acids, metabolic syndrome, pharmaceutical formulations


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