Ultra-fast liquid chromatography with tandem mass spectrometry determination of eight bioactive components of Kai-Xin-San in rat plasma and its application to a comparative pharmacokinetic study in normal and Alzheimer's disease rats

Ginseng, the root of the Panax ginseng, has been a popular and widely-used traditional herbal medicine in Korea, China, and Japan for thousands of years. Now it has become popular as a functional health food and is used globally as a natural medicine. Evidence is accumulating in the literature on the physiological and pharmacological effects of P. ginseng on neurodegenerative diseases. Possible ginseng- or ginsenosides-mediated neuroprotective mechanisms mainly involve maintaining homeostasis, and anti-inflammatory, anti-oxidant, anti-apoptotic, and immune-stimulatory activities. This review considers publications dealing with the various actions of P. ginseng that are indicative of possible neurotherapeutic efficacies in neurodegenerative diseases and neurological disorders such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis and multiple sclerosis.

For millennia, ginseng and some of its components have been used to treat a wide variety of medical conditions, including age-related memory impairment. Because of its purported effects and apparently low rate of side effects, ginseng remains one of the top selling natural product remedies in the United States. Given its potential role for improving age-related memory impairments and its common use in China for the treatment of Alzheimer's disease-like symptoms, we analyzed the effects of commercially available preparations of ginseng on the accumulation of the Alzheimer's amyloid beta peptide (Abeta) in a cell-based model system. In this model system, ginseng treatment resulted in a significant reduction in the levels of Abeta in the conditioned medium. We next examined the effects of several compounds isolated from ginseng and found that certain ginsenosides lowered Abeta concentration in a dose-dependent manner with ginsenoside Rg3 having an approximate IC50 of under 25 microM against Abeta42. Furthermore, we found that three of these isolated components, ginsenoside Rg1, Rg3, and RE, resulted in significant reductions in the amount of Abeta detected in the brains of animals after single oral doses of these agents. The results indicate that ginseng itself, or purified ginsenosides, may have similarly useful effects in human disease.

Compound K is a major metabolite of ginsenoside Rb1, which has various pharmacological activities in vivo and in vitro. However, previous studies have focused on the pharmacokinetics of a single metabolite or the parent compound and have not described the pharmacokinetics of both compounds in humans. To investigate the pharmacokinetics of ginsenoside Rb1 and compound K, we performed an open-label, single-oral dose pharmacokinetic study using Korean Red Ginseng extract. We enrolled 10 healthy Korean male volunteers in this study. Serial blood samples were collected during 36 h after Korean Red Ginseng extract administration to determine plasma concentrations of ginsenoside Rb1 and compound K. The mean maximum plasma concentration of compound K was 8.35±3.19 ng/mL, which was significantly higher than that of ginsenoside Rb1 (3.94±1.97 ng/mL). The half-life of compound K was 7 times shorter than that of ginsenoside Rb1. These results suggest that the pharmacokinetics, especially absorption, of compound K are not influenced by the pharmacokinetics of its parent compound, except the time to reach the maximum plasma concentration The delayed absorption of compound K support the evidence that the intestinal microflora play an important role in the transformation of ginsenoside Rb1 to compound K.