Pharmacokinetics and pharmacodynamics study of Panax notoginseng saponins in mice with Parkinson’s disease by using UPLC-MS/MS combined with microdialysis / 中草药

ABSTRACT

Objective: To investigate the changes in the content of notoginsenoside R1 (R1), ginsenoside Rg1(Rg1) and amino acid neurotransmitters in brain micro dialysate after the treatment with Panax notoginseng saponins (PNS) solution in Parkinson’s disease (PD) model mice induced by 1-methylmethyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Methods: Mice were injected intraperitoneally with MPTP to induce PD mice model. After intravenous injection of PNS solution, brain micro dialysate was collected by microdialysis technique. The sample was divided into two parts, one was subjected to pharmacokinetic study of R1 and Rg1 by UPLC-MS/MS, and the other part for pharmacodynamics study which was done by pre-column derivatization of the amino acids and HPLC-FLD analysis. Results: After iv administration of PNS to the mice, the maximum CSF concentration was (35.48 ± 24.4) ng/mL for R1 and (75.61 ± 41.35) ng/mL for Rg1. The time to reach maximum concentration was found 1.75 h both for R1 and Rg1. The AUC value of R1 and Rg1 were (100.12 ± 84.29) ng∙h/mL and (218.84 ± 144.73) ng∙h/mL, respectively. Moreover, the levels of aspartic acid and glutamic acid were reduced, and glycine, taurine and γ-aminobutyric acid levels were increased in PD model mice treated with PNS in comparison with model group. Conclusion: PNS can enter the brain through the blood brain barrier (BBB) to some extent, and regulate the imbalance of amino acid level in PD model mice, so as to display the neuroprotective effect and its therapeutic value.