Ginseng (Asian) (Panax ginseng)

Asian ginseng (Panax ginseng) has been used for thousands of years and appears in the first known Chinese Materia Medica (thought to have been written during the Han Dynasty, 220 BCE). The English word “ginseng” stem from the Chinese word rénshēn. Rén means person, while shēn means plant root. Ginseng’s pronunciation comes from Cantonese “yun sum” or the Hokkien pronunciation "jîn-sim". Ginseng is a slow-growing perennial plant with fleshy roots and belongs to the genus Panax of the family Araliaceae. The genus Panax derives its name from the Greek words pan (all) and akos (healing).
There are a total of 13 species that grow widely in Asia, North America and Europe. Asian ginseng root is native to the northern mountainous regions of Korea, China, and parts of the Russian Federation. Cultivation of Panax ginseng in Korea started around 11 B.C. by transplantation of wild ginseng. Panax ginseng cultivated in Korea (Korean ginseng) is harvested after 4-6 years of cultivation, and it is classified into three types depending on how it is processed: (a) fresh ginseng (less than 4 yrs. old; can be consumed in its fresh state); (b) white Ginseng (4-6 yrs. old; dried after peeling); and (c) red ginseng (harvested when 6 yrs. old, and then steamed and dried) is an herb native to East Asia and Russia.
Panax ginseng should not be confused with American ginseng (Panax quinquefolius) or Siberian ginseng (Eleutherococcus senticosus), which have different medicinal properties. It should also not be confused with Panax notoginseng which also has different properties and is a key ingredient in the TCM formula Yunnan baiyao.

Ginseng (Asian) (Panax ginseng)

Uses

Panax ginseng It is also cultivated for its medicinal properties and the root is widely used as a “Yang” tonic in traditional Chinese medicine. Patients take ginseng to improve athletic performance, strength, and stamina, and as an immunostimulant. Some use it to treat diabetes, cancer, HIV/AIDS, and a variety of other conditions. Ginsenosides, the saponin glycosides, are thought responsible for medicinal effects of P. ginseng. They have both stimulatory and inhibitory effects on the CNS, alter cardiovascular tone, and increase humoral and cellular-dependent immunity.

Chemistry/Pharmacology

Approximately 200 substances have been isolated from Asian ginseng thus far. Recent phytochemistry and pharmacological studies have discovered a variety of potent components in all parts of the ginseng plant including ginsenosides, alkaloids, phenolics, phytosterol, carbohydrates, polypeptides, ginseng oils, amino acids, nitrogenous substances, vitamins, minerals, and certain enzymes. Ginsenosides are the major bioactive metabolites. There is a total of 38 ginsenosides in Panax ginseng. Ginsenosides are triterpene saponins. Most consist of a dammarane skeleton (17 carbons in a four-ring structure) with different sugar groups (e.g., glucose, rhamnose, xylose and arabinose) connected to the C-3 and C-20 positions.
So far, more than 70 ginsenosides have been separated from the three main kinds of ginseng. Among them, ginsenosides Rbl, Rb2, Rc, Rd, Rgl, Rg2, and Re are the major constituents of white and red ginseng, while ginsenosides Rg3, Rg5, and Rg6 are unique to red ginseng. Some rare ginsenosides, like the ocotillol saponin F11 (24-R-pseudoginsenoside) and the pentacyclic oleanane saponin Ro (3,28-O-bisdesmoside) have also been isolated and identified. The quality and composition of ginsenosides in the ginseng plants are influenced by several factors including the species, age, part of the plant, cultivation method, harvesting season and storage method. Using ginsenoside Rf as example, Rf is exclusive to Asian ginseng whereas F11 is unique to American ginseng. Thus, the Rf/F11 ratio is applied as a phytochemical label to differentiate American from Asian ginseng. Many reports indicate that ginsenoside metabolites show better biological effects than ginsenosides. For example, Rh2 and PD, metabolites of Rg3, have more potent anti-tumor activities than ginsenoside Rg3. Unlike Ginsenosides Rb1, Rb2, Rg1 and Re, compound K, PT and PD, the intestinal metabolites of PPTs and PPDs, have inhibitory effects like that of the human liver enzyme cytochrome P450 inhibitory effects.

Clinical Studies

Increasing Longevity. Historically, ginseng has been thought to prolong lifespan. Recently, several studies have shown that the components of ginseng can prolong the life span of experimental models such as Drosophila and C.elegans. While ginseng does not significantly prolong the lifespan of aging mice, it has been shown to stabilize mice’s behavior by antagonizing stress.
Increase in oxygen-derived free radicals is closely related to the aging process. Reactive oxygen species are produced by intracellular molecular pathways located mainly in the cytoplasm and mitochondria. Asian ginseng has been shown to decreases lipid peroxidation and restore antioxidant potential by reducing oxidative stress in rats. Ramesh T et. al. showed that aged rats fed with a Korean red ginseng water extract diet exhibited much less oxidative damage. Ginseng’s antioxidant effects have also been clinically proven. Kim HG et. al. demonstrated in a double-blind randomized controlled clinical trial, that administration of Korean ginseng led to a significant decrease in the levels of serum reactive oxygen species (ROS) and methane dicarboxylic aldehyde (MDA), while potentiating the total glutathione content and glutathione reductase (GSH-Rd) activity.
Cardiovascular Health. Aging is also associated with various, complicated and changes in cardiovascular structure and function. The heart becomes slightly hypertrophic and has a dampened response to sympathetic stimuli, including increase in heart rate and myocardial contractility. The aorta and central elastic arteries become dilated and stiff, exhibiting enhanced pulse wave velocity, endothelial dysfunction and biochemical transformation that resembles early atherosclerosis. To compensate for the decrease in arterial compliance and increase in peripheral resistance, the heart must pump with greater force. The myocardium responds in much the same way as other muscles do after exposure to increased load - enlargement and hypertrophy that result in a gradual increase in cardiac weight There is a gradual decrease in cardiac myocytes, while remaining myocytes become hypertrophic, and the myocardium shows increased levels of collagen. Yuan SM et. al. has shown that Asian ginseng to be cardioprotective through its anti-oxidative, anti-arrhythmic, calcium channel-antagonistic, anti-inflammatory, and anti-apoptotic properties.
Another major cardiovascular effect of ginseng is endothelial regulation, which plays an important in role in the alteration of blood vessels with age. The endothelium is the innermost layer of blood vessels that comes into direct contact with the blood. It is composed of a single layer of squamous epithelial cells, which are regular and smooth in children and young adults, offering minimal resistance to blood flow. With age, the endothelial layer starts to have atypically shaped cells and becomes thickened due to smooth muscle fibers that migrate from the tunica media. This thickening not only contributes to a reduction in arterial elasticity and compliance, but also the lumen size, further increasing resistance to blood flow. A clinical trial by Jovanovski E et. all demonstrates that Korean red ginseng and its ginsenosides significantly improved flow mediated vasodilatation post treatment.
Nervous System and motor function. There is a progressive loss of neural tissue with age, usually reflected by a gradual decline in cognitive function. With age, cerebral blood flow decreases by around 20%. There is also an age-related decline in the synthesis of many neurotransmitters and their receptors. These include the catecholamines (adrenaline and noradrenalin), dopamine and serotonin. These reductions can slow reaction time, impair information processing and, sometimes, increase the risk of depression. Neurodegenerative disorders occur when cells fail to react to age-related increases in oxidative, metabolic, and ionic stress, consequently resulting in the accumulation of damaged proteins, deoxyribonucleic acid (DNA) and cell membranes. Ginseng has been commonly applied and studied for its enhancement of cognition enhancing and stress reduction. The underlying molecular mechanisms of ginseng’s effects on the brain have been widely studied. Ong WY. et. al. found Asian ginseng beneficial effects on cognition to involve monoamine transmission, glutamatergic transmission, estrogen signaling, nitric oxide production, the Keap1/Nrf2 adaptive cellular stress pathway, neuronal survival, apoptosis, neural stem cells and neuroregeneration, microglia, astrocytes, oligodendrocytes and cerebral microvessels.
Immunity. As the adaptability of the immune system declines accordingly with age, it is less able to respond properly to invasion of foreign agent. Such changes in defenses result in immune vulnerability. Both Korean and American ginseng have been reported to have immune-regulatory properties. Several studies suggest Asian ginseng may enhance immune functioning in various populations. Cho YJ et. al. in a clinical trial showed Y-75 (Ginsan), an acidic polysaccharide extracted from Korean Panax ginseng, to be an immunomodulator that significantly increased NK cell cytotoxic activity and enhanced phagocytic activity of peripheral blood cells as well as serum TNF-α levels.
Anti-Cancer properties. Ginseng has also been investigated for potential anticancer properties. Ginsenosides exhibit antiproliferative effects in vitro. Epidemiological data in breast cancer patients show improved survival and quality of life with ginseng use, and reduced risk of endometrial cancer in breast cancer survivors. In addition, two case-controlled studies indicate a positive association between consumption and reduction in the incidence of all cancers. Small, randomized studies suggest safety and effectiveness of ginseng for reducing genotoxicity and improving quality of life in patients with epithelial ovarian cancer.

Biomechanical Mechanism

Ginseng and its components, especially ginsenosides, is not only effective in antiaging, but also beneficial in aging-related neurological disorders, including Alzheimer's disease. In senescence-accelerated mouse prone 8 (SAMP8) mice model, 3 months administration with ginsenoside Rg1 significantly reduced the contents of soluble Aβ1-40 in the hippocampus and decreased hippocampal PKA RIIα (isoform IIα of the regulatory subunit of PKA) levels. Consequently, learning and memory improvement was evident, suggesting long-term application of ginsenoside Rg1 may postpone cognitive decline via increasing Aβ generation, PKA/CREB activity, as well as brain derived neurotrophic factor (BDNF) content in the brain.
Animal studies suggest ginsenosides prolong drug-induced sleeping time in mice and exhibit additional depressant effects on the CNS. In addition, the ginsenoside Rb1 improves acetylcholine release and enhances postsynaptic uptake of choline. In other animal studies, ginseng saponins lowered total plasma cholesterol and triglyceride levels. Ginseng may improve nitric oxide synthesis in endothelium of the heart, lung, kidneys, and in the corpus cavernosum.
In humans, oral intake of ginseng reduced post-exercise muscle injury and inflammation marked by reduced creatine kinase, beta-glucuronidase, and glucose-6-phosphate dehydrogenase.
Anticancer activity has been observed in vitro with several ginsenosides. Differentiation of HL-60 promyelocytic cells was induced in ginsenosides Rh2- and Rh3-treated cells. Rg3 exerted effects in part by blocking the nuclear translocation of the protein ß-catenin in colon cancer cells, most of which turned cancerous via activation of the Wnt/ß-catenin signaling pathway. Rp1 reduced breast cancer cell proliferation by decreasing stability of the insulin like growth factor 1 receptor protein in breast cancer cells.

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