Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Sichuan Academy of Chinese Medical Sciences, Chengdu 610041, China.
Fitoterapia. 2020 Nov;147:104735. doi: 10.1016/j.fitote.2020.104735. Epub 2020 Sep 30.
Ursolic acid (UA) is a natural pentacyclic triterpenoid compound existing in various traditional Chinese medicinal herbs, and it possesses diverse pharmacological actions and some undesirable adverse effects, even toxicological activities. Due to UA's low solubility and poor bioavailability, and its interaction with gut microbiota after oral administration, the pharmacokinetics of UA remain elusive, leading to obscurity in the pharmacokinetics-pharmacodynamics (PK-PD) profile and relationship for UA. Based on literatures from PubMed, Google Scholar, ResearchGate, Web of Science and Wiley Online Library, with keywords of "pharmacology", "toxicology", "pharmacokinetics", "PK-PD" and "ursolic acid", herein we systematically review the pharmacology and toxicity of UA, and rethink on its pharmacokinetics on the basis of PK-PD model, and seek to delineate the underlying mechanisms for the characteristics of pharmacology and toxicology of UA, and for the pharmacokinetic features of UA particularly from the organ tropism and the interactions between UA and gut microbiota, and lay a solid foundation for development of UA-derived therapeutic agents in clinical settings.
熊果酸（UA）是一种天然五环三萜化合物，存在于各种中草药中，具有多种药理作用和一些不良的不良反应，甚至毒理学活性。由于 UA 的溶解度低、生物利用度差，以及口服后与肠道微生物群的相互作用，UA 的药代动力学仍然难以捉摸，导致 UA 的药代动力学-药效学（PK-PD）特征和关系不明确。基于 PubMed、Google Scholar、ResearchGate、Web of Science 和 Wiley Online Library 的文献，以“药理学”、“毒理学”、“药代动力学”、“PK-PD”和“熊果酸”为关键词，本文系统综述了 UA 的药理学和毒理学，并基于 PK-PD 模型重新思考其药代动力学，试图阐明 UA 的药理学和毒理学特征以及 UA 的药代动力学特征的潜在机制，特别是从器官趋向性和 UA 与肠道微生物群之间的相互作用方面，为临床开发 UA 衍生的治疗剂奠定基础。
