Affiliation:
1. School of Pharmacy, Binzhou Medical University, Yantai 264003, China
2. School of Pharmacy, Shandong University of Traditional
Chinese Medicine, Jinan 250300, China
Abstract
Background:
Cycloastragenol (CAG) is a sapogenin derived from the main bioactive constituents of
Astragali Radix (AR). However, the current research on CAG metabolism in vivo and in vitro is still inadequate, and
the metabolite cluster is incomplete due to incomplete analysis strategy.
Objective:
The objective of this study was to screen and identify the metabolic behavior of CAG in vivo and in vitro.
Methods:
A simple and rapid analysis strategy based on UHPLC-Q-Exactive Orbitrap mass spectrometry combined
with data-mining processing technology was developed and used to screen and identify CAG metabolites in rat body
fluids and tissues after oral administration.
Results:
As a result, a total of 82 metabolites were fully or partially characterized based on their accurate mass, characteristic
fragment ions, retention times, corresponding Clog P values, and so on. Among the metabolites, 61 were
not been reported in previous reports. These metabolites (6 metabolites in vitro and 91 in vivo) were generated
through reactions of hydroxylation, glucuronidation, sulfation, hydrogenation, hydroxylation, demethylation,
deisopropylation, dehydroxylation, ring cleavage, and carboxyl substitution and their composite reactions, and the
hydroxylation might be the main metabolic reaction of CAG. In addition, the characteristic fragmentation pathways
of CAG were summarized for the subsequent metabolite identification.
Conclusion:
The current study not only clarifies the metabolite cluster-based and metabolic regularity of CAG in
vivo and in vitro, but also provides ideas for metabolism of other saponin compounds.
Funder
Shandong Province Chinese herbal medicine and decoction piece standard research topic
Yantai campus integration development project
Binzhou Medical University Scientific Research Fund for High-level Talents
Young and Creative Team for Talent Introduction of Shandong Province
Youth Project of Shandong Provincial Natural Fund
Medical and Health Technology Development Plan at Shandong Province
Key project at central government level: The ability establishment of sustainable use for valuable Chinese medicine resources
Publisher
Bentham Science Publishers Ltd.
Subject
Clinical Biochemistry,Pharmacology
Reference27 articles.
1. Yeh T.S.; Chuang H.L.; Huang W.C.; Chen Y.M.; Huang C.C.; Hsu M.C.; Astragalus membranaceus improves exercise performance and ameliorates exercise-induced fatigue in trained mice. Molecules 2014,19(3),2793-2807
2. Yang F.X.; Wang Y.; Xia P.F.; Yang R.J.; Wang Y.X.; Zhang J.; Fan Q.; Zhao L.; Review of chemical constituents,pharmacological effects and clinical applications of Danggui Buxue Decoction and prediction and analysis of its Q-markers. Zhongguo Zhongyao Zazhi 2021,46(11),2677-2685
3. Wang J.; Wu M.L.; Cao S.P.; Cai H.; Zhao Z.M.; Song Y.H.; Cycloastragenol ameliorates experimental heart damage in rats by promoting myocardial autophagy via inhibition of AKT1-RPS6KB1 signaling. Biomed Pharmacother 2018,107,1074-1081
4. Gu M.; Zhang S.; Zhao Y.; Huang J.; Wang Y.; Li Y.; Fan S.; Yang L.; Ji G.; Tong Q.; Huang C.; Cycloastragenol improves hepatic steatosis by activating farnesoid X receptor signalling. Pharmacol Res 2017,121,22-32
5. Lee S.Y.; Chang W.L.; Li Z.X.; Kirkby N.S.; Tsai W.C.; Huang S.F.; Ou C.H.; Chang T.C.; Astragaloside VI and cycloastragenol-6- O -beta-D-glucoside promote wound healing in vitro and in vivo. Phytomedicine 2018,38,183-191