scholarly journals Transforming of Triptolide into Characteristic Metabolites by the Gut Microbiota

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 606
Author(s):  
Ran Peng ◽  
Shu-Rong Ma ◽  
Jie Fu ◽  
Pei Han ◽  
Li-Bin Pan ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Gut Microbiota ◽  
Theoretical Basis ◽  
High Performance ◽  
Ion Trap ◽  
Liver Microsomes ◽  
Tandem Mass ◽  
Molecular Weights ◽  
Intestinal Contents ◽  
First Time

The importance of the gut microbiota in drug metabolism, especially in that of nonabsorbable drugs, has become known. The aim of this study was to explore the metabolites of triptolide by the gut microbiota. With high-performance liquid chromatography coupled with tandem mass spectrometry and ion trap time-of-flight multistage mass spectrometry (LC-MS/MS and LC/MSn-IT-TOF), four metabolites of triptolide (M1, M2, M3, and M4) were found in the intestinal contents of rats. M1 and M2, were isomeric monocarbonyl-hydroxyl-substituted metabolites with molecular weights of 390. M3 and M4 were isomeric dehydrogenated metabolites with molecular weights of 356. Among the four metabolites, the dehydrogenated metabolites (M3 and M4) were reported in the gut microbiota for the first time. The metabolic behaviors of triptolide in the gut microbiota and liver microsomes of rats were further compared. The monocarbonyl-hydroxyl-substituted metabolites (M1 and M2) were generated in both systems, and another monohydroxylated metabolite (M5) was found only in the liver microsomes. The combined results suggested that the metabolism of triptolide in the gut microbiota was specific, with two characteristic, dehydrogenated metabolites. This investigation might provide a theoretical basis for the elucidation of the metabolism mechanism of triptolide and guide its proper application in clinical administration.

Profiling of Cyclic Hexadepsipeptides Roseotoxins Synthesized In Vitro and In Vivo: A Combined Tandem Mass Spectrometry and Quantum Chemical Study

2003 ◽  
Vol 9 (2) ◽  
pp. 105-116 ◽  
Author(s):  
Alexandr Jegorov ◽  
Béla Paizs ◽  
Martin Žabka ◽  
Marek Kuzma ◽  
Vladimír Havlíček ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Quantum Chemical ◽  
High Performance ◽  
Ion Trap ◽  
Quantum Chemical Study ◽  
Ion Cyclotron Resonance ◽  
Tandem Mass

High-performance liquid chromatography and tandem mass spectrometry (HPLC/MS/MS) was used for the detection of cyclic hexadepsipeptides roseotoxins produced by Trichothecium roseum. Roseotoxins were found in both submerged standard cultivation on Czapek–Dox medium and in vivo cultivation extract obtained from an apple. Roseotoxin chromatographic profiles from these two experiments were compared. Product-ion collision-induced dissociation (CID) spectra obtained on an ion trap (electrospray ionisation, ESI) were used for the identification of natural roseotoxins A, B, C and of minor destruxins A and B. The dissociation behavior of roseotoxins is discussed in terms of a fragmentation scheme proposed for describing the dissociation pathways of cyclic peptides. This scheme involves opening of the cyclopeptide ring via formation of oxazolone derivatives and fragmentation of the resulting linear species, which have a free N-terminus and an oxazolone ring at the C-terminus. Some aspects of this fragmentation scheme are underlined by modeling the dissociation channels of roseotoxin A using quantum chemical calculations. The structures of roseotoxin A and destruxin B were verified by nuclear magnetic resonance (NMR) spectroscopy. Structures of three new minor natural roseotoxins [Val4]RosA, [MeLxx4]RosA and [MeLxx4]RosB were deduced by ion cyclotron resonance Fourier transform mass spectrometry (ICR-FT-MS) and ion trap tandem mass spectrometry by examining the pre-separated roseotoxin fraction.

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