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植物三萜类化合物和类固醇在胆汁酸代谢、转运及信号传导中的作用:药理学和毒理学意义。

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

作者信息

Luo Zichen, Zhou Wei, Xie Tong, Xu Weichen, Shi Chen, Xiao Zihan, Si Yu, Ma Yan, Ren Qingling, Di Liuqing, Shan Jinjun

机构信息

Medical Metabolomics Center, Institute of Pediatrics, Jiangsu Key Laboratory of Children's Health and Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.

State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China.

出版信息

Acta Pharm Sin B. 2024 Aug;14(8):3385-3415. doi: 10.1016/j.apsb.2024.04.027. Epub 2024 May 3.

Abstract

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

摘要

胆汁酸(BAs)由宿主肝脏从胆固醇合成,并输送至肠道,在肠道中它们会经历肠道微生物的进一步代谢,并通过各种转运蛋白在肝脏和肠道之间循环。它们用于乳化膳食脂质,并作为信号分子,通过特定受体调节宿主的代谢和免疫稳态。因此,胆汁酸代谢、转运和信号传导的紊乱与胆汁淤积、代谢紊乱、自身免疫性疾病等密切相关。植物三萜类化合物和类固醇与胆汁酸具有结构相似性,并且已发现它们可调节胆汁酸的代谢、转运和信号传导,可能发挥药理或毒理作用。在此,我们更新了关于胆汁酸的研究进展,特别强调新发现的微生物胆汁酸。此外,还突出了针对胆汁酸代谢和信号传导进行疾病治疗的最新进展。随后,研究了植物三萜类化合物在胆汁酸代谢、转运和信号传导中的作用,通过这些机制分析它们潜在的药理、毒理或药物相互作用效应。最后,提出了一种研究范式,利用肠道微生物群作为纽带,来解释这些重要天然产物在胆汁酸信号传导中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a53/11365449/cee873c2958e/ga1.jpg

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