Characterization of the Metabolic Fate of Datura metel Seed Extract and Its Main Constituents in Rats

Abstract

Datura metel L. has been frequently used in Chinese traditional medicine. However, little is known on the chemical composition and in vivo metabolism of its seeds. In this study, using the strategy “chemical analysis, metabolism of single representative compounds, and metabolism of extract at clinical dosage” that we propose here, 42 constituents were characterized from D. metel seeds water extract. Furthermore, the metabolic pathways of 13 representative bioactive compounds of D. metel seeds were studied in rats after the oral administration of D. metel seeds water extract at a clinical dosage (0.15 g/kg). These included three withanolides, two withanolide glucosides, four amides, one indole, one triterpenoid, one steroid, and one sesquiterpenoid, and with regard to phase II metabolism, hydroxylation, (de)methylation, and dehydrogenation reactions were dominant. Furthermore, the metabolism of D. metel seeds water extract provided to rats at a clinical dosage was investigated by liquid chromatography-tandem mass spectrometry based on the above metabolic pathways. Sixty-one compounds were detected in plasma, 83 in urine, and 76 in fecal samples. Among them, withanolides exhibited higher plasma exposure than the other types. To our knowledge, this is the first systematic study on the chemical profiling and metabolite identification of D. metel seeds, including all compounds instead of single constituents.

UPLC-MS/MS Identification and Quantification of Withanolides from Six Parts of the Medicinal Plant Datura Metel L.

“…It was first obtained from a methanol extract of the whole plant of D. metel L. in 1987. Subsequently, the literature reports that this compound can also be isolated from the seeds of D. metel L. [17,18]. The quantitative parts of our experiment also show that the content of compound 80 is generally high in seeds.…”

“…An ACQUITY UPLC TM (Waters Corp., Milford, MA, USA) system in tandem with a Triple TOF TM 5600 + mass spectrometer (ABsciex, Framingham, MA, USA.) was acquired for qualitative analysis using a UPLC C 18…”

Alkaloids of the Genus Datura: Review of a Rich Resource for Natural Product Discovery

“…A pentafluorophenyl phase column has also been used to analyze tropane alkaloids [10] following the recognition that this column type is more retentive toward positively-charged analytes [80,81], and can be used in both reversed-phase and hydrophilic interaction chromatography (HILIC) modes. UH-PLC columns [36,77] have also been used for profiling of alkaloids; UHPLC columns have smaller particle sizes to provide more efficient separations, often with shorter analysis times. Common polar mobile phases for HPLC-MS and UHPLC-MS include water/methanol or water/acetonitrile, with formic acid (0.1-3%), acetic acid, or ammonium formate [82][83][84] added.…”

“…Profiling of Datura alkaloids using LC separations coupled to mass spectrometry (LC-MS) has been performed on a variety of mass spectrometry platforms including triple-quadrupole [10], ion trap [65], hybrid triple-quad/linear ion trap [36], time-of-flight (ToF) [75], quadrupole time-of-flight (QToF) hybrid, or orbitrap instruments [32,36,77,85]. Ionization usually has involved electrospray ionization (ESI), although APCI (atmospheric pressure chemical ionization) has also been used [16,84].…”

“…In 2020, four racemic indole alkaloids (daturametelindoles 3-6) were isolated from an ethanolic extract of D. metel seeds by Liu et al [47] who used 2D-NMR, chiral LC, polarimetry, and circular dichroism spectra to resolve structures and stereochemistry. Interestingly, the n-butyl ether of compound 5, to the outsider, appears to be a potential artifact of isolation, as n-butanol was used during fractionation, but a 2019 study of rodent metabolism of D. metel metabolites detected 5 in an aqueous extract of the seeds (where no n-butanol was used), suggesting that the nbutyl group occurs naturally in the plant [77]. Cuscohygrine ( 13) results from condensation of oxobutanoate ester 18 (Figure 6) with 17, followed by decarboxylation, [99] although labeling studies suggest it can also be formed from 12 [63].…”