An integrated strategy based on LC/MS for the systematic screening of loganin metabolites in vivo

Abstract

Loganin is an active compound derived from Cornus officinalis Sieb. et Zucc., which has been widely used due to its excellent pharmacological effects including anti-diabetic, anti-inflammatory, neuroprotective, and anti-tumor properties. However, the metabolic process of loganin in vivo is insufficiently elucidated until now. Therefore, a metabolic networking cluster combined with multiple data processing techniques based on UHPLC-MS was applied to predict the metabolites of loganin and explore their temporal dynamic change patterns. First, the target ions in the blank and dosed groups were systematically screened using the Compound Discoverer (CD) software. Then, the potential metabolites were identified based on the workflow of CD. Second, a metabolic networking cluster (MNC) was proposed to predict the metabolites of loganin according to the related reports in the literature and existing metabolites of loganin. Third, the establishment of diagnostic product ions (DPIs) was used to preliminarily screen and identify the potential metabolites of loganin. As a result, 2 critical metabolites, including loganin and loganetin, were proposed as networking cluster cores, and a total of 34 metabolites were screened and characterized. Results indicated that loganin primarily underwent the deglucosylation, glucuronidation, demethylation, sulfation, and dehydroxylation reactions and their composite reactions in vivo. In addition, most metabolites reached their peak concentration between 0.5 and 1 h and then gradually decreased, indicating that the metabolic process of loganin in rats was relatively rapid. In summary, an integrated strategy was proposed to comprehensively elucidate the metabolic pathways of loganin in vivo, which provides a vital reference for research on the metabolism of other compounds.