Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai R&D Centre for Standardization of Chinese Medicines, 1200 Cailun Road, Shanghai, 201203, China.
Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai R&D Centre for Standardization of Chinese Medicines, 1200 Cailun Road, Shanghai, 201203, China.
Environ Toxicol Pharmacol. 2021 Jul;85:103628. doi: 10.1016/j.etap.2021.103628. Epub 2021 Feb 27.
Dictamnine (DIC), a typical furan-quinoline alkaloid, has a wide range of pharmacological and toxicological effects, such as anti-bacterial, antifungal, anti-cancer, and hepatoxicity. But the molecular mechanism of DIC-induced hepatoxicity in mice remains unclear. This study aimed to clarify the biotransformation patterns of DIC in vitro/in vivo and the relative molecular mechanism of DIC-induced hepatoxicity in mice. All metabolites of DIC were identified by comparing the blank and drug-containing urine, feces, plasma, and liver samples. The structure of epoxide intermediate derived from DIC was confirmed by trapping assay. Oxidative stress injury and inflammation have been confirmed to be involved in the toxicological process of DIC-induced hepatoxicity in mice by detecting the relative biochemical indexes. The results will help to develop a deeper understanding about the biotransformation patterns of DIC, structure of the epoxide intermediate, and the molecular mechanism of DIC-induced hepatoxicity in mice.
冬凌草甲素（DIC）是一种典型的呋喃喹啉生物碱，具有广泛的药理和毒理作用，如抗菌、抗真菌、抗癌和肝毒性。但是，DIC 诱导的小鼠肝毒性的分子机制尚不清楚。本研究旨在阐明 DIC 在体外/体内的生物转化模式，以及 DIC 诱导的小鼠肝毒性的相对分子机制。通过比较空白和含药尿液、粪便、血浆和肝组织样品，鉴定了 DIC 的所有代谢产物。通过捕获试验，确认了 DIC 衍生的环氧化物中间体的结构。通过检测相对生化指标，证实氧化应激损伤和炎症参与了 DIC 诱导的小鼠肝毒性的毒理学过程。这些结果将有助于深入了解 DIC 的生物转化模式、环氧化物中间体的结构以及 DIC 诱导的小鼠肝毒性的分子机制。
