Metabolites Identification of Bioactive Compounds Daturataturin A, Daturametelin I, N-Trans-Feruloyltyramine, and Cannabisin F From the Seeds of Datura metel in Rats

Abstract

Datura metel L. is a widely used traditional herbal medicine, and withanolides and amides are the two groups of main bioactive constituents in Datura metel seeds. This study aimed to elucidate the metabolism of four representative bioactive compositions containing daturataturin A (1), daturametelin I (2), N-trans-feruloyltyramine (3), and cannabisin F (4) in rats. After separately oral administration of 20 mg/kg withanolides (1, 2) and amides (3, 4) to rats, a total of 12, 24, and 21 metabolites were detected in the plasma, urine, and fecal samples, respectively. Among them, three hydroxylated metabolites, 1-M3, 2-M2, and 3-M5, were detected in plasma and rat liver microsome incubation system in high abundance. Two metabolites of 1 and 2 were unambiguously identified by comparing with reference standards. Particularly, the methylated metabolite 27α-methoxy-(22R)-22,26-epoxy-27-[(β-D-glucopyranosyl)oxy]ergosta-2,4,6,24-tetraene-1,26-dione (daturametelin L) is a new compound. The withanolides could readily get hydroxylation or methylation metabolism. Meanwhile, the phase II metabolism (glucuronidation or sulfation) was the major reaction for the amides. This is the first study on in vivo metabolism of these active compounds in seeds of Datura metel.

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

“…The pure compounds daturametelindole B ( 1 ), daturametelin M ( 3 ), hyoscyamilactol ( 5 ), daturametelindole A ( 9 ), daturametelin L ( 29 ), daturametelindole D ( 18 ), n -trans-feruloyltyramine ( 19 ), daturametelindole C ( 22 ), daturametelin I ( 30 ), cannabisin F ( 31 ), daturaolone ( 32 ), daturataturin A ( 36 ), n -trans-p-coumaroyltyramine ( 40 ), and stigmasterol ( 41 ) were isolated from the seeds of D. metel by the authors. Their structures were characterized using nuclear magnetic resonance and MS (Figure 2 and Supplementary Figures S3–S22; Xu et al, 2018). Dinoxin B ( 10 ), withametelin L ( 13 ), and cinerolide ( 20 ) were purchased from Nantong Feiyu Biological Technology Co., Ltd. (Nanjing, China).…”

“…Plasma, urine, and fecal samples were prepared as described in our previous report (Xu et al, 2018). The residue of these samples was dissolved in 300 μL of methanol, and filtered through a 0.22-μm membrane for ultra-high performance liquid chromatography coupled with electrospray ionization (UPLC/ESI) qTOF-MS analysis.…”

“…The qTOF/MS system was equipped with an ESI source operating in positive ion mode, as in our previous report (Xu et al, 2018). High-purity nitrogen (N 2 ) and high-purity helium (He) were used as desolvation gas and collision gas, respectively.…”

“…Therefore, metabolites’ identification is critical for elucidating the bioactivities of complex herbal medicines. Recently, we studied the metabolism of two typological components, including two amides ( n -trans-feruloyltyramine and cannabisin F) and two withanolide glucosides (daturataturin A and daturametelin I) of D. metel seeds in rats (Xu et al, 2018). To fully predict and identify their metabolites, we selected seven main types of representative compounds from the seeds.…”

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

“…Daturafoliside K shows a pronounced effect against NO production [5]. Daturataturin A exhibits cytotoxic activity against SW-620 and MDA-MB-435 cell lines, and potential immunosuppressive activity [6,7].…”