Pharmacokinetics of ginsenoside Rg1 in rat medial prefrontal cortex, hippocampus, and lateral ventricle after subcutaneous administration

Abstract

The present study aimed to investigate pharmacokinetics of Rg1 in rat medial prefrontal cortex (mPFC), hippocampus (HIP), and lateral ventricle (LV) after subcutaneous injection. For the first time, intracerebral pharmacokinetics of Rg1 was studied in freely moving rats by microdialysis technique. Rg1 concentrations in dialysates were detected by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method and were revised using in vivo probe-recovery in HIP and LV. The pharmacokinetic parameters were then determined using non-compartmental models. Since the in vivo recoveries remained stable in HIP and LV during 9 h dialysis, average recoveries were used to revise dialysate concentrations. After dosing, Rg1 was soon detected in brain extracellular fluid (bECF) and cerebrospinal fluid (CSF). The elimination of Rg1 was significantly slower in mPFC than in HIP and LV, and significantly greater AUC was obtained in mPFC than in HIP. Rg1 kinetics in bECF and CSF indicate that Rg1 can go across the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), and then immediately distribute to learning and memory-related regions in brain, which may lead to rapid pharmacological onset. There may be active transport and target-mediated disposition of Rg1 in the CNS, which need to be further clarified.

Classical Active Ingredients and Extracts of Chinese Herbal Medicines: Pharmacokinetics, Pharmacodynamics, and Molecular Mechanisms for Ischemic Stroke

“…Xue et al studied the pharmacokinetics of Rg1 in the medial prefrontal cortex (mPFC), hippocampus (HIP), and lateral ventricle (LV) of rats after subcutaneous injection. The results showed that the elimination of Rg1 in the mPFC group was significantly slower than that in the HIP and LV groups, and the AUC was significantly higher than that in the HIP group [81]. Feng et al clarified that Rg1 can be easily distributed to most tissues.…”

Ginsenoside Rg1 modulates medial prefrontal cortical firing and suppresses the hippocampo-medial prefrontal cortical long-term potentiation

“…This lack of reversal may be explained by the pharmacokinetics of Rg1 as illustrated by a recent report that highlighted the idea that mPFC is the putative site of action of Rg1. In that recent report, analysis of dialysates by LC-MS/MS showed that following a single subcutaneous injection of Rg1 (40 mg/kg), the elimination of this ginsenoside was lower in the mPFC with a significantly higher area under the curve value as compared to the hippocampus and the lateral ventricle [32] . However, the lack of reversal might also be attributable to the duration of our recordings.…”

Identification of Chemical Components of Qi-Fu-Yin and Its Prototype Components and Metabolites in Rat Plasma and Cerebrospinal Fluid via UPLC-Q-TOF-MS

“…Similarly, the prototype components and metabolites in the cerebrospinal fluid after oral administration of Qi-Fu-Yin have not been reported. Several research showed that some saponins in GRR [ 55 , 56 ], GRP [ 57 ], and phthalides in ASR [ 58 , 59 ] can be absorbed into the cerebrospinal fluid. In addition, saponins in GRR [ 60 ] and GRP [ 61 ], flavonoids in ZSS [ 62 ], and source esters in PRP [ 53 ] have been determined in the brain tissue homogenate.…”