Ginseng (Order: Apiales, Family: Araliaceae, Genus: Panax) has been used as a traditional herbal medicine for over 2000 years, and is recorded to have antianxiety, antidepressant and cognition enhancing properties. The protective effects of ginseng on neurological disorders are discussed in this review. Ginseng species and ginsenosides, and their intestinal metabolism and bioavailability are briefly introduced. This is followed by molecular mechanisms of effects of ginseng on the brain, including glutamatergic transmission, monoamine transmission, estrogen signaling, nitric oxide (NO) production, the Keap1/Nrf2 adaptive cellular stress pathway, neuronal survival, apoptosis, neural stem cells and neuroregeneration, microglia, astrocytes, oligodendrocytes and cerebral microvessels. The molecular mechanisms of the neuroprotective effects of ginseng in Alzheimer’s disease (AD) including β-amyloid (Aβ) formation, tau hyperphosphorylation and oxidative stress, major depression, stroke, Parkinson’s disease and multiple sclerosis are presented. It is hoped that this discussion will stimulate more studies on the use of ginseng in neurological disorders.
Ginseng (Order: Apiales, Family: Araliaceae, Genus: Panax) roots, stems, and leaves have been used as traditional herbal medicine for over 2000 years. In Korea, China and Japan, ginseng is the most valuable of all medicinal herbs. Its anti-anxiety, antidepressant and cognition-enhancing effects has been recorded by Shi-Zhen Li in Ben Cao Gang Mu (本草纲目) which is the most comprehensive pre-modern herbal text, compiled during the Ming Dynasty in China. Panax ginseng (人參) is mostly cultivated in Korea, the Manchuria region of China (“dong bei”) and the coastal region of Siberia due to its sensitivity to temperature and soil conditions. Panax quinquefolium L (American ginseng, 西洋參) is cultivated in southern Canada and the USA, and Panax notoginseng (田七) is grown in the Yunnan and Guangxi provinces of China. These three herbs represent the most extensively investigated species of Panax. The latter means “cure all”, and constituents of ginseng root produce adaptogenic, restorative, immunomodulatory, vasodilatory, anti-inflammatory, antioxidant, anti-aging, anticancer, anti-fatigue, anti-stress and anti-depressive effects in rodents and humans (Attele et al., 1999; Shin et al., 2000; Chang et al., 2003; Choo et al., 2003; Cheng et al., 2005; Wang et al., 2009). The bioactive ingredients in ginseng root include more than 60 ginsenosides, e.g., Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1, Rg2, and Rg3, as well as polysaccharides, fatty acids, oligopeptides and polyacetylenic alcohols (Qi et al., 2010). The purpose of this review is to discuss the effects of ginseng on the normal brain, and its protective effects in neurological disorders such as Alzheimer’s disease (AD), major depression, stroke, Parkinson’s disease and multiple sclerosis. It is hoped that will stimulate more studies on the use of ginseng in neurological disorders.
Conclusions and Future Directions
Many ginsenosides have been isolated and characterized. The molecular mechanisms associated with ginsenosides involve scavenging free radicals, inhibition of inflammation, and prevention of excitotoxicity. Animal and cell culture studies have indicated that ginsenosides have different activities in both physiological and pathologic conditions. The structure activity relationship of ginsenosides has not been fully elucidated. However, it is becoming increasingly evident that ginsenosides produce neuroprotective effects by reducing free radical production and enhancing brain function. Studies involving each ginsenoside should include mechanisms of action, specificity, structure and function relationship, detailed pharmacokinetics and toxicity studies, and therapeutic studies in animal models and humans. Further studies are necessary to examine the effects of ginseng on metabotropic glutamate receptors and transporters, and the Keap1/Nrf2 adaptive cellular pathway. The neurological disorders for which there is most evidence from pre-clinical and a small number of clinical studies to benefit from ginseng are AD and major depression, and clinical trials are necessary to confirm the efficacy of ginseng and ginsenosides in the prevention and treatment of these, and possibly other neurological conditions.