Role of Ginseng in Atherosclerosis, Inflammation, and Cancer
Ginseng root has been used in Chinese and Korean cultures since ancient times. The plant belongs to the genus Panax, which has been in use in traditional medicine over centuries. The name ginseng comes from the Chinese words “Jen Sheng”, meaning “man-herb”, because of the humanoid shape of the root of the plant, which is the part most commonly consumed (1).
There are varieties of ginseng based upon the origin of plant from Korea, China and America. Traditionally, wild ginseng that grows naturally in mountains was handpicked and was used for medicinal purposes, but today with rising trends of its usage, cultivated varieties have also been introduced. These days, not only the fresh varieties but processed varieties (white and red ginseng) with improved shelf life are also available in the market. It is available as powders as well as extracts. Ginseng is predominantly produced in Canada, South Korea, and the U.S. Some of the top exporters of ginseng are Canada, South Korea, China, Hong Kong, and the United States. China is one of the leading ginseng consumers (2). According to an estimate, in terms of value, the global ginseng market is projected to experience a healthy compound annual growth rate of 4.8% between years 2018 and 2027. This may be due to globalization, increased consumer acceptance for oriental and Asian flavors and demand for Chinese herbal medicine (3).
With rising trends of functional foods, there have been recent advances in studying the health and pharmacological properties of ginseng root. It has been found to have following health benefits
* Antidiabetic properties
* Aids in weight loss
* Protects against cardiovascular problems
* Anti-inflammatory actions
* Protects against cancer
Active components of ginseng
Two basic functional compounds, Ginsenoside and Gintonin, have been identified in ginseng roots. Ginsenosides are steroid glycosides belonging to dammarane family of molecules. Many studies suggest that ginsenosides have antioxidant properties. They have been observed to increase internal antioxidant enzymes and act as a free-radical scavenger. In addition, they have been suggested to haveneuroprotective properties and could be useful against neurodegenerative diseases such as Alzeimer’s and Parkinson’s. These effects have been explained by the fact that these compounds are similar to steroid hormones and may act as partial agonists of steroid hormone receptors. Gintonin is a glycolipoprotein fraction derived from ginseng which is also known to be protective against neurodegenerative diseases and cancer (1, 4).
Atherosclerosis is a complex disease characterized by buildup of plaque insidethe walls of arteries which may be a base for cardiovascular and stroke related events. Exposure of arteries to certain environmental toxins including high LDL-C (low Density Lipoprotein- Cholesterol), high blood glucose levels, high blood pressure and tobacco can result in endothelial dysfunction leading to atherosclerosis. Inflammation of vascular walls is regarded as an important event in atherosclerosis. Local inflammation of vascular wall mainly triggered by dyslipidemia (specifically high LDL-C and remnant lipoprotein levels) is often a trigger for starting an atherosclerotic lesion. This vascular injury expresses adhesion molecules which results in release of chemokines and cytokines. These chemicals attract circulating monocytes to injured part of vessel and monocytes attach to endothelium in interaction with adhesion molecules. Monocytes eventually mature to form macrocytes. In case of high LDL-C, macrophages uptake the LDL-C which gets oxidized leading to foam cell formation. This complex proliferates because of release of several growth factors by endothelium. The vascular smooth muscle cells also get involved which slowly enhances the thickness of intima (inner most layer of wall) of vessel. This thickening of vascular wall is called atherosclerosis (10). It not only leads to thickening of wall, rather decreases the size of lumen for blood flow. In severe cases, large plaques may result in complete blockage of vessel which cuts off the blood supply to its target organ. Plaques may even rupture, triggering a cascade of blood clotting factors which lead to blood clot formation (thrombosis) at site of injury, thus further narrowing the artery for supplying oxygen rich blood to other cells (11).
Ginseng is effective in preventing atherosclerosis because of its role in following two mechanisms: 1) chronic inflammation (which is discussed in next section), 2) preventing oxidation of LDL-C
Protection of LDL-C against oxidative modification
Peroxisome proliferator-activated receptor γ (PPARγ), modulated by ginseng, have been studied to enhance PON1 (Serum paraoxonase-1) gene expression. As a result of this gene expression, the protein (PON 1) formed is a serum enzyme involved protecting lipids against oxidation through breakdown of lipid peroxides. Therefore, it saves the damage to vascular wall caused by oxidation of LDL-C, thus decreasing the chances of plaque formation and atherosclerosis (12, 13, 14).
Chronic inflammation is a complex pathological condition which is baseline for several diseases including atherosclerosis, rheumatoid arthritis, inflammatory bowel syndrome, multiple sclerosis, asthma and psoriasis (15). Role of ginseng in decreasing the blood levels of inflammatory cytokines has been studied. In a Korean research, feeding 60mg/kg/day to cancer patients resulted in decrease in proinflammatory cytokines in blood (16). Ginseng plays a role in preventing inflammatory diseases by modulating the expression of PPAR-γ.These PPARγ agonists have been shown to have systemic anti-inflammatory effects through decreased secretion of proinflammatory cytokines, Interleukin-6, interleukin-1b and Tumor Necrosis Factor- α (TNF-α) (15).
Ginseng plays a role in mitigating cancer through anti-inflammatory and anti-oxidant properties and its role in apoptotic mechanisms (17). Cancer is an alteration in cell cycle resulting from higher rates of proliferation and poor differentiation. By acting as PPARγ agonist, ginseng may have antiproliferative effect on malignant cells. PPARγalso promotes the terminal differentiation of malignant cells (5).
Ginseng has a potential role in treating several chronic conditions. At cellular levels, majority of these roles are a result of modulation of PPARγ by the active components of ginseng. Increasing the use of ginseng as herb or as extract is likely to control the rising rates of non-communication diseases.