Screening and Identification of the Main Metabolites of Schisantherin a In Vivo and In Vitro by Using UHPLC-Q-TOF-MS/MS

Abstract

Schisantherin A is an active ingredient originating from Schisandra chinensis (Turcz.) which has hepatoprotective and anti-oxidation activities. In this study, in vitro metabolisms investigated on rat liver microsomes (RLMs) and in vivo metabolisms explored on male Sprague Dawley rats of Schisantherin A were tested, respectively. The metabolites of Schisantherin A were identified using ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). Based on the method, 60 metabolites were successfully identified and structurally characterized including 48 phase-I and 12 phase-II metabolites. Among the metabolites, 45 metabolites were reported for the first time. Moreover, 56 and eight metabolites were detected in urine and bile and 19 metabolites were identified in rats’ plasma. It demonstrated that hepatic and extra-hepatic metabolic pathways were both involved in Schisantherin A biotransformation in rats. Five in vitro metabolites were structurally characterized for the first time. The results indicated that the metabolic pathways mainly include oxidation, reduction, methylation, and conjugation with glucuronide, taurine, glucose, and glutathione groups. This study provides a practical strategy for rapidly screening and identifying metabolites, and the results provide basic data for future pharmacological and toxicology studies of Schisantherin A and other lignin ingredients.

Screening of Q-markers for the wine-steamed Schisandra chinensis decoction pieces in improving allergic asthma

“…3 G and Table 1 ). The metabolite of Schisantherin A is used as an example to illustrate the speculated cracking process based on reference [ 23 ], as shown in Fig. 4 .…”

“…The molecular ions at m/z 415.1751 [M + H-H 2 O] + , m/z 384.1572 [M + H-H 2 O-OCH 3 ] + , m/z 369.1326 [M + H-H 2 O-OCH 3 -CH 3 ] + , m/z 345.1315 [M + H-H 2 O-C 5 H 10 ] + , m/z 301.1074 [M + H-H 2 O-CO 2 -C 5 H 10 ] + and m/z 286.0847 [M + H-H 2 O-CO 2 -C 5 H 10 -CH 3 ] + conformed to the fragmentation pattern of m/z 433.185. Based on these results, Compound 11 was identified as 6-debenzoyl-Schisantherin A [ 23 ].…”

“…The formula of Compound 12 was determined to be C 22 H 26 O 8 , which was only 14 Da lower in atomic mass than schisantherin A. Fragments of m/z 401.1632 [M + H-H 2 O] + , m/z 369.1361 [M + H-H 2 O-CH 3 OH] + , m/z 331.1193 [M + H-H 2 O-C 5 H 10 ] + , and m/z 316.0941 [M + H-H 2 O-C 5 H 10 -CH 3 ] + were detected. Thus, Compound 12 was identified as 3-demethylation-6-debenzoyl-Schisantherin A [ 23 ].…”

Metabolite Profiling of Swertia cincta Extract in Rats and Pharmacokinetics Study of Three Bioactive Compounds Using UHPLC-MS/MS

“…Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) isUHPLC-MS is a useful way to study the metabolites of traditional Chinese medicine [9]. TraditionalDue to traditional Chinese medicines contain numerousmedicine having many components with, low contentcontents of some components, and similar structures.…”

Research Progress on the Pharmacological Action of Schisantherin A

“…Sch A has the highest content and the most effective advantage in the lignan extract of S. chinensis [ 15 , 16 ]. In a 2019 study, the metabolic profiles of Sch A in vitro (rat liver microsomes) and in vivo (rat plasma, urine, and bile) were assessed by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) [ 17 ]. Sch A was found to be more complex in vivo than in vitro and undergo both hepatic and extrahepatic metabolic pathways in its biotransformation.…”