Abstract
Linarin, a flavone glycoside, is considered to be a promising natural product due to its diverse pharmacological activities, including analgesic, antipyretic, anti-inflammatory and hepatoprotective activities. In this research, the metabolites of linarin in rat intestinal flora and biosamples were characterized using ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS/MS). Three ring cleavage metabolites (4-hydroxybenzoic acid, 4-hydroxy benzaldehyde and phloroglucinol) were detected after linarin was incubated with rat intestinal flora. A total of 17 metabolites, including one ring cleavage metabolite (phloroglucinol), were identified in rat biosamples after oral administration of linarin. These results indicate that linarin was able to undergo ring fission metabolism in intestinal flora and that hydrolysis, demethylation, glucuronidation, sulfation, glycosylation, methylation and ring cleavage were the major metabolic pathways. This study provides scientific support for the understanding of the metabolism of linarin and contributes to the further development of linarin as a drug candidate.
Highlights
Linarin is a naturally occurring flavonoid and it has been isolated from several medicinal plants, such as Flos chrysanthemiindici, Buddleja officinalis, Cirsium setosum, Mentha arvensis and Buddleja davidii
By comparing the accurate molecular masses and mass fragmentations of the metabolites with those of linarin and reference standards, five metabolites, including three ring cleavage metabolites (Figure 1, Table 1), were identified after linarin was incubated with intestinal flora, and a total of 17 metabolites of linarin, including one ring cleavage metabolite (Figure 2, Figure S1, Table 1), were identified in rat urine, feces, plasma and bile
Three ring cleavage metabolites were detected after linarin was incubated with intestinal flora
Summary
Linarin (acacetin-7-O-β-D-rutinoside) is a naturally occurring flavonoid and it has been isolated from several medicinal plants, such as Flos chrysanthemiindici, Buddleja officinalis, Cirsium setosum, Mentha arvensis and Buddleja davidii. Our previous pharmacokinetic study showed that the absolute bioavailability of linarin was 0.47%, which indicated that linarin underwent extensive metabolism after oral administration [8]. A comprehensive metabolism study of linarin is needed and the detailed metabolic fate of linarin will provide the scientific basis for the development of linarin as a potential therapeutic. To the best of our knowledge, to date only two studies associated with the metabolism of linarin have been completed. The identification and structural elucidation of the metabolites of linarin in rat urine was reported in our previous study using liquid chromatography-ion trap mass spectrometry (LC-IT-MSn ) [9]. Six urinary metabolites were identified, urine being the only matrix evaluated
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