Pharmacokinetics and dopamine/acetylcholine releasing effects of ginsenoside Re in hippocampus and mPFC of freely moving rats

Abstract

Aim: To investigate the pharmacokinetics and dopamine/acetylcholine-releasing effects of ginsenoside Re (Re) in brain regions related to learning and memory, and to clarify the neurochemical mechanisms underlying its anti-dementia activity. Methods: Microdialysis was conducted on awake, freely moving adult male SD rats with dialysis probes implanted into the hippocampus, medial prefrontal cortex (mPFC) or the third ventricle. The concentrations of Re, dopamine (DA) and acetylcholine (ACh) in dialysates were determined using LC-MS/MS. Results: Subcutaneous administration of a single dose of Re (12.5, 25 or 50 mg/kg) rapidly distributed to the cerebrospinal fluid and exhibited linear pharmacokinetics. The peak concentration (C max ) occurred at 60 min for all doses. Re was not detectable after 240 min in the dialysates for the low dose of 12.5 mg/kg. At the same time, Re dose-dependently increased extracellular levels of DA and ACh in the hippocampus and mPFC, and more prominent effects were observed in the hippocampus. Conclusion: The combined study of the pharmacokinetics and pharmacodynamics of Re demonstrate that increase of extracellular levels of DA and ACh, particularly in the hippocampus, may contribute, at least in part, to the anti-dementia activity of Re.

Ginsenoside compound K suppresses the abnormal activation of T lymphocytes in mice with collagen-induced arthritis

“…Meyer, Family Arawww.nature.com/aps Liu KK et al Acta Pharmacologica Sinica npg liaceae) is frequently used as a crude substance in Asian countries in food products and as a medicinal ingredient [15,16] . Ginsenosides, the major components of ginseng, exhibit various biological activities, including anti-inflammatory, anti-dementia, and anti-tumor effects [17][18][19] . The protopanaxadiol ginsenosides Rb1, Rb2, and Rc are metabolized to compound K (C-K; Figure 1) by intestinal bacteria in humans and rats [20][21][22] .…”

Changes in intestinal microbiota affect metabolism of ginsenoside Re

“…Ginsenoside Re (G‐Re, shown in Figure ), as the most abundant constituent of ginseng, is often considered characteristic of the total ginseng saponins and is used to study the intestinal metabolism of ginseng, its pharmacological activity and mechanism of action. However, similar to many saponins and flavonoid glycosides, polarized glycans in the G‐Re structure limit its absorption in the intestine, leading to low bioavailability (<0.19–0.28%; Shi, Xue, Zhao, & Li, ). Potentially, the activity of such compounds can be further improved, and thus, improvement in the absorption and metabolism of G‐Re has become a research hotspot in recent years.…”

White Ginseng Protects Mouse Hippocampal Cells Against Amyloid-Beta Oligomer Toxicity

“…It also ameliorates immobilization stress‐induced memory deficits by inducing mRNA expression of brain‐derived neurotrophic factor in the rat hippocampus (Lee et al ., ). A combined study of pharmacokinetic and pharmacodynamics study shows that ginsenoside Re stimulates to release of hippocampal dopamine and acetylcholine, it may contribute to antidementia effects of ginsenoside Re (Shi et al ., ). It is detected in cerebrospinal fluid by passing through the blood brain barrier after subcutaneous injection (Shi et al ., ).…”