Panax ginseng, or Asian ginseng, is a plant cultivated in much of the eastern Asian countries, especially in northeast China. The root of the plant has been used for centuries in traditional medicine and continues to be widely used for its medicinal benefits such as clearing the mind of “excessive mental chattering” and “eliminates evil qi” (Dharmananda, 2002). Furthermore, clinical studies such as those conducted by Kiefer, et al., have shown that, in controlled settings, ginseng is effective in improving many areas ranging from the immune system to erectile dysfunction. While clinical studies in the past document the effects of ginseng macroscopically and ancient Chinese medicinal texts base medicinal qualities of the plant in a philosophical manner rather than a scientific one, I am more curious about the major chemical constituents in ginseng, ginsenosides, or saponins from ginseng, and their biochemical interactions inside the body that contribute to ginseng’s medicinal effects, specifically on the nervous system.
As technology in the agriculture and biotechnology sectors have advanced dramatically over time, availability of ginseng has made it much easier to isolate and characterize its chemical constituents. Chemical isolation was fruitless until the 1960s, when chemists first isolated oleanolic acid, a ginsenoside. (Tang & Eisenbrand, 1992). Since then, around two hundred substances, ranging from ginsenosides to peptides and carbohydrates, have been isolated from Panax ginseng. (Kim, 2012).
The chemical compounds that give ginseng its vast medicinal qualities are the class of ginsenosides, which are both unique and abundant throughout the whole plant: roots, leaves, berries, and flower buds. There are also several variations of ginsenosides: dammarane-type (further classified into protopanaxadiols [PPD] and protopanaxatriols [PPT]), ocotillol-type and oleanane-type oligoglycosides, and polysaccharides (Kim, 2012). Ginsenoside diversity is a consequence of differences in functional groups and their placements and chemical structure which will not be covered in-depth. Ginsenosides are diverse molecules that can trigger diverse effects. With over twenty ginsenosides and each ginsenoside having multiple effects on specific tissue (Tsang et al., 1985), ginseng can affect and/or regulate processes throughout the body, especially on the central nervous system.
Ginsenosides have numerous effects on the central nervous system, much of which are beneficial than harmful. In regards to memory and learning, ginsenosides have shown to facilitate these processes in a study conducted by Yumi Takemoto, et al. in which a very specific ginsenoside, “20(S)-protopanaxadiol glycosides with two glucosyl moieties,” promotes nerve fiber production. Likewise, the GRb1 ginsenoside alters neuronal membrane properties by uptaking mitotic inhibitors or by affecting tubulin assembly. Ginsenosides like Rb1 and Rg1 prevent scopolamine-induced memory deficits: Rb1 exhibits increased uptake of choline and facilitated the release of acetylcholine (Attele et al., 1999). Choline, a water-soluble nutrient, is neurotransmitter essential to many neuronal functions, including muscle control and memory (link), and is a precursor to acetylcholine, another neurotransmitter that has an important role in learning and memory (link).
The protective powers of ginseng extend to resisting neurological disorders which include Alzheimer’s disease and Parkinson’s disease (Ong, et al., 2015). These diseases are characterized with a progressive loss of cognitive function and motor disabilities, respectively. Genetic factors like mutations, unhealthy lifestyle, and other environmental factors may contribute to the pathogenesis of such diseases (Farooqui, 2010). Studies on age accelerated mice treated with the ginsenoside gintonin decreased the release of Aβ1–42, amyloid-beta proteins, which are the proteins that create buildup in the brain, forming plaques and causing Alzheimer’s diseases. Gintonin also thinned plaque build-up and weakened the effects of memory impairment in a mouse model (Hwang et al., 2012b). As for the effects on Parkinson’s, ginsenosides Rb1, Rg1, Rd, and Re have neuroprotective effects by means of oxidative stress and neuroinflammation inhibition and reduction in toxin-induced apoptosis (Ong et al., 2015). Moreover, ginsenosides reduced the loss of dopaminergic neurons, or neurons specialized in the production of dopamine. The excessive loss of dopaminergic neurons in the substantia nigra, which houses 3-5% of total neurons in its specific region of the brain, leads to Parkinson’s disease (Chinta, et al., 2005 link). In a study with mouse cells treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a precursor to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+), that specially targets and destroys dopaminergic neurons in the substantia nigra of the brain (Przedborski et al., 1996 link ), the ginsenoside panaxtriol saponins, derived from provided neuroprotection against the loss of dopaminergic neurons and behavioral impairment through suppressing over-expression of inflammatory factors, especially cyclooxygenase-2 (COX-2), an enzyme which exacerbates MPTP-induced neurotoxicity by perpetuating an inflammatory response cycle (Luo et al., 2011link ). Ginsenosides have functions in protecting neurons and inhibiting destructive mechanisms which would otherwise causes neurological disorders like Alzheimer’s disease and Parkinson’s disease.
Ginsenosides also have other effects on the central nervous system that are not conclusive. A study on rats given a ginsenoside concoction of Rb1, Rb2, and Rc while under sedative-hypnotic-induced sleep resulted in the rats for sleeping longer than the sedative time is usually for hexobarbital. In another study, rats sensitized to morphine and then given total saponin saw a halt in dopaminergic hyperfunction and the further development of dopamine receptor supersensitivity induced by chronic administration of morphine (Kim et al., 1994 link). As a result of these studies, ginsenosides both act as stimulants and depressants on the central nervous system.
Just like many other drugs, ginseng is a pharmakon. As the root is widely available and used by many, it is important to shed light on the health risks that ginseng poses when used inappropriately. “Ginseng abuse syndrome” is a term coined by Ronald K. Siegel to denote the toxic effects long-term users may experience when ingesting too much of the plant at a time. Siegel reported in his clinical trials that a small percentage of users experienced depression, insomnia, or anxiety. Although Siegel’s report is disorganized and scientifically off base (Bergner, 2000), it does not mean that ginseng does not cause any adverse side effects. Ginseng is known, to both western and traditional medicine, to cause headache, insomnia, heart palpitations, and hypertension.