Bile Acid Signaling in Metabolic and Inflammatory Diseases and Drug Development

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 76(6), P. 1221 - 1253

Published: July 8, 2024

Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction daily turnover in humans. Biliary secretion generates flow and facilitates biliary lipids, endogenous metabolites, xenobiotics. In intestine, facilitate digestion absorption dietary lipids fat-soluble vitamins. Through activation nuclear receptors G protein-coupled interaction with gut microbiome, critically regulate host metabolism innate adaptive immunity involved pathogenesis cholestasis, metabolic dysfunction-associated steatotic liver disease, alcohol-associated type-2 diabetes, inflammatory bowel diseases. their derivatives have been developed as potential therapeutic agents treating chronic diseases gastrointestinal disorders. SIGNIFICANCE STATEMENT: solubilization lipid absorption, immunity, modulate microbiome. Targeting signaling holds promise

Language: Английский

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Bifidobacterium pseudolongum‐Derived Bile Acid from Dietary Carvacrol and Thymol Supplementation Attenuates Colitis via cGMP‐PKG‐mTORC1 Pathway

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 23, 2024

Carvacrol and thymol (CAT) have been widely recognized for their antimicrobial anti-inflammatory properties, yet specific effects on colitis the mechanisms involved remain insufficiently understood. This study establishes a causative link between CAT administration mitigation, primarily through enhancement of Bifidobacterium pseudolongum abundance in colon. increase promotes production secondary bile acids, particularly hyodeoxycholic acid (HDCA) 12-ketodeoxycholic (12-KCAC), which exert effects. Notably, does not alleviate symptoms germ-free mice, indicating necessity gut microbiota. research uncovers novel regulatory mechanism where HDCA 12-KCAC inhibit colonic inflammation by reducing expression transmembrane guanylate cyclase 1A epithelium. downregulation elevates intracellular Ca

Language: Английский

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The role of botanical triterpenoids and steroids in bile acid metabolism, transport, and signaling: Pharmacological and toxicological implications

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(8), P. 3385 - 3415

Published: May 3, 2024

Bile acids (BAs) are synthesized and released by the host liver from cholesterol delivered to intestine, where they undergo further metabolism gut microbes circulate between intestines through various transporters. They serve emulsify dietary lipids act as signaling molecules, regulating host's immune homeostasis specific receptors. Therefore, disruptions in BA metabolism, transport, closely associated with cholestasis, metabolic disorders, autoimmune diseases, others. Botanical triterpenoids steroids share structural similarities BAs, have been found modulate signaling, potentially exerting pharmacological or toxicological effects. Here, we updated research progress on BA, a particular emphasis new-found microbial BAs. Additionally, latest advancements targeting for disease treatment highlighted. Subsequently, roles of botanical examined, analyzing their potential pharmacological, toxicological, drug interaction effects these mechanisms. Finally, paradigm is proposed that utilizes microbiota link interpret role important natural products signaling.

Language: Английский

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Digestive dynamics: Unveiling interplay between the gut microbiota and the liver in macronutrient metabolism and hepatic metabolic health

Physiological Reports, Journal Year: 2024, Volume and Issue: 12(12)

Published: June 1, 2024

Although the liver is largest metabolic organ in body, it not alone functionality and assisted by "an inside an organ," gut microbiota. This review attempts to shed light on partnership between microbiota metabolism of macronutrients (i.e., proteins, carbohydrates, lipids). All nutrients absorbed small intestines are delivered for further metabolism. Undigested food that enters colon metabolized produces secondary metabolites, which into portal circulation reach liver. These microbiota-derived metabolites co-metabolites include ammonia, hydrogen sulfide, short-chain fatty acids, bile trimethylamine N-oxide. Further, several compounds, such as acids can alter microbial composition, turn influence health. focuses these their host physiology. Furthermore, briefly delineates effect portosystemic shunt microbiota-liver axis, current understanding treatments target axis.

Language: Английский

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Promiscuous acyltransferases for ester and amide synthesis in aqueous solution

Catalysis Today, Journal Year: 2024, Volume and Issue: 442, P. 114925 - 114925

Published: July 9, 2024

Hydrolases are well-known for hydrolyzing esters, amides, carbamates, peptides, or acid anhydrides in the presence of water. However, some them also capable catalyzing reverse reaction (condensation) under certain conditions aqueous systems. Hence, these enzymes called promiscuous hydrolases/acyltransferases. This review deals with their discovery, background information on mechanism action, and significant improvements by enzyme engineering to both enhance product formation decrease undesired hydrolysis targeted acyl products. Their applications biocatalysis exemplified synthesis a wide range esters amides systems, including preparative-scale processes combination hydrolases/acyltransferases other cascade reactions utilize alternative feedstocks from renewable resources, example. Complementary, use ATP-dependent amide synthesizing is covered. Together, represent practically useful alternatives well-established chemical reactions, operating solutions that appeal different industries.

Language: Английский

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