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

Abstract

Ziziphi Spinosae Semen (ZSS), a traditional Chinese medicine, is used in clinics for the treatment of insomnia in China and other Asian countries. Herein, we described for the first time a comparative pharmacokinetics study of the six major compounds of ZSS in normal control (NC) and para -chlorophenylalanine (PCPA)-induced insomnia model (IM) rats that were orally administered the aqueous extract of ZSS. An ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass (UHPLC-Q-Orbitrap-MS) method was developed and validated for the simultaneous determination of coclaurine, magnoflorine, spinosin, 6 ‴ -feruloylspinosin, jujuboside A (JuA), and jujuboside B (JuB) in ZSS in rat plasma. The established approach was successfully applied to a comparative pharmacokinetic study. The systemic exposures of spinosin and 6 ‴ -feruloylspinosin were decreased in the IM group compared to the NC group, while plasma clearance (CL) was significantly increased. The T max values of JuA and JuB in IM rats were significantly lower than those in NC rats. The T 1/2 of JuA in the IM group was significantly accelerated. The pharmacokinetic parameters of coclaurine and magnoflorine were not evidently affected between the two groups. These results indicate that the pathological state of insomnia altered the plasma pharmacokinetics of spinosin, 6 ‴ -feruloylspinosin, JuA, and JuB in the ZSS aqueous extract, providing an experimental basis for the role of ZSS in insomnia treatment. The comparative pharmacokinetics-based UHPLC-Q-Orbitrap-MS using full-scan mode can therefore provide a reliable and suitable means for the screening of potentially effective substances applied as quality markers of ZSS.

Mechanisms Underlying the Action of Ziziphi Spinosae Semen in the Treatment of Insomnia: A Study Involving Network Pharmacology and Experimental Validation

“…Over 150 different components have been separated and identified from ZSS, including saponins, flavonoids, alkaloids, and polysaccharides. Total saponins and compounds from ZSS are well known for their significant sedative and hypnotic effects (Du et al, 2020). Until now, the pharmacological investigation of total saponins for the treatment of insomnia has mainly focused on jujubosides, jujuboside A, jujuboside B, and other monomers.…”

Comparative pharmacokinetic study of six lignans in normal and diabetic rats after oral administration ofSaururus chinensisextract by LC–MS/MS

“…Meanwhile, the CL of (-)-(7R,8R)-machilin D in diabetic rats was significantly decreased compared with that in normal rats (P < 0.05), suggesting a slower elimination of (-)-(7R,8R)-machilin D in diabetic rats (Du et al, 2020). In contrast, the AUC 0 !…”

The pharmacology, pharmacokinetics, and toxicity of spinosin: A mini review

“…The rat oral administration of ZJS extract (20 g/kg) containing spinosin revealed the pharmacokinetic parameters with C max at 224 ± 82 μg/L, T max at 5.5 ± 0.6 h, and T 0.5 at 5.8 ± 0.9 h in rat plasma using the HPLC method ( Li et al, 2003 ). The pharmacokinetic parameters of spinosin in ZJSP between the control group (NC) and insomnia model (IM) group were determined using the UPLC-MS method, and the results showed no significant differences between the two groups, but an increasing trend for CL and the decreasing trend for the AUC 0-t and AUC 0-∞ of spinosin in the IM group, which indicated the faster and poorer absorption of spinosin in the IM group ( Du et al, 2020 ). The Yin-deficiency rats were given ZJS by gavage, spinosin was detectable in the small intestine, stomach, liver, brain, large intestine, spleen, lung, heart, kidney, and blood within 10 min, and it sustained for 240 min ( Guo, 2014 ).…”