Degradation Kinetics of 6‴-p-Coumaroylspinosin and Identification of Its Metabolites by Rat Intestinal Flora

Abstract

6‴-p-Coumaroylspinosin (P-CS), a bioactive flavonoid, is typically extracted from Semen Ziziphi Spinosae (SZS). In this study, a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed to determine P-CS for investigating the degradation characteristics of P-CS incubated with rat feces. The results showed that P-CS degraded rapidly and the degradation speeds varied depending upon the P-CS concentrations (3, 15, and 30 μg/mL). The degradation of P-CS processes follow first-order kinetics. On the basis of the mass spectrometry (MS) spectrum mode of the product ions, two main metabolites of P-CS were identified. Swertisin was the main metabolite at 3 and 15 μg/mL, while spinosin was produced when the P-CS concentration was 30 μg/mL. Spinosin and swertisin could improve mRNA transcription levels of glutamate receptor K1, K2, and K3 (GluK1, GluK2, and GluK3) subunits in rat hippocampal neurons. In addition, they showed an obvious synergistic effect in this respect. Collectively, the results can be used to explain the metabolic and pharmacological mechanisms of P-CS.

Comparative pharmacokinetics of six major compounds in normal and insomnia rats after oral administration of Ziziphi Spinosae Semen aqueous extract

“…Compared to that of spinosin, the CL value (928.92 ± 309.06 L/h/kg) of 6 ‴ -feruloylspinosin remarkably increased ( P < 0.01), indicating that 6 ‴ -feruloylspinosin might be rapidly and widely distributed in rats, aligning with the finding of a previous report [ 10 ]. Some studies reported that 6 ‴ -feruloylspinosin was first hydrolyzed to spinosin and swertisin, and spinosin could be further metabolized to swertisin in vitro by rat intestinal bacteria [ 25 , 26 ]. Based on our knowledge, we speculate that spinosin and swertisin might be the major and high content compounds in plasma.…”

Efficacy of the Jingxin Zhidong Formula for Tic Disorders: A Randomized, Double Blind, Double Dummy, Parallel Controlled Trial

“…[33][34][35] Notably, several components of the JXZDF, including Semen Ziziphi Spinosae, Radix Bupleuri, Fructus Aurantii and Angelica Dahurica are potentially effective at modulating gut microbiota abundances. [36][37][38][39] Further studies could be designed to assess the gut microbiota to reveal the underlying pharmacological and therapeutic effects of JXZDF for the treatment of TD.…”

Gastrointestinal Absorption and Metabolic Dynamics of Jujuboside A, A Saponin Derived from the Seed of Ziziphus jujuba

“…The hippocampal neurons from Sprague–Dawley rats (postnatal 1–3 days) were prepared and cultured referring to the reported method . The purity of the neurons was evaluated through immunofluorescence staining .…”

“…The hippocampal neurons from Sprague−Dawley rats (postnatal 1−3 days) were prepared and cultured referring to the reported method. 29 The purity of the neurons was evaluated through immunofluorescence staining. 30 The hippocampal neurons were cultured for 8 days and rinsed with ice phosphate buffer solution (PBS).…”