Identification of the metabolites of nimbolide in rat by liquid chromatography combined with quadrupole/orbitrap mass spectrometry

Biomedical Chromatography, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 4, 2024

Nimbolide is a major furanoid compound isolated from Azadirachta indica. The aim of this study was to characterize the metabolites nimbolide in rats and propose metabolic pathways. were generated by incubating (10 μM) with rat liver microsomes, nicotinamide adenine dinucleotide phosphate (NADPH), nucleophiles (glutathione [GSH] or N-acetyl-lysine [NAL]) at 37°C for 60 min. For vivo study, intravenously administered single dose 10 mg/kg, bile urine collected. identified ultra-high-performance liquid chromatography-quadrupole/orbitrap mass spectrometry (UPLC-Q/Orbitrap-MS) using electrospray ionization positive ion mode. Totally, nine detected, their identities characterized accurate MS MS/MS data. In GSH-supplemented GSH conjugation primary elimination pathway. furan ring bioactivated into cis-butene-1,4-dial that can be trapped GSH. NAL-supplemented two NAL conjugates (M4 M5) derived observed. urine, N-acetyl-cysteine, cysteine-glycine, conjugate also found. current provides an overview metabolism bioactivation profiles rats, which aids understanding its safety activity.

Language: Английский

Current mechanistic insights into Withaferin A: a promising potential adjuvant anticancer agent from Withania somnifera

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 30, 2024

Language: Английский