What is ginseng?
Ginseng is a traditional herb that has been used for centuries in Chinese medicinal practices as an all-healing tonic. There are several types of ginseng belonging to the genus Panax, Panax ginseng and American ginseng (Panax quinquefolius) are the major forms. Ginseng plants are grown in mountainous regions in cool climates and their roots are used for medicinal purposes.
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Ginseng root can be used fresh or in dried form and can be prepared by steaming. Traditionally ginseng is used in combinations with other herbs to supplement the body.
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The active constituents of ginseng are thought to be chemicals known as saponins or triterpenoid glycosides. These saponins have been named ginsenosides and it is thought there are more than 30 different ginsenosides present in ginseng root. Other compounds are also present in ginseng root such as polysaccharides and gintonin.
What are the health benefits of ginseng?
Ginseng is traditionally reported to supplement the five viscera and is thought to prolong life and sharpen the wits. These statements likely relate to the opinion of ginseng as an adaptogen and a stimulant to boost energy levels. Many ginseng-containing traditional remedies use decoctions (brewed teas) containing additional herbal extracts. It is therefore not clear whether ginseng is the key herb having the major effect or whether these combinations are essential for activity.
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Currently many companies market products containing ginseng and suggest that consumption of ginseng is linked to health benefits such as increased energy and mood, anti-stress, support for the immune system. The World Health Organisation (WHO) monographs on medicinal herbs [1] list traditional uses of ginseng for coughs, fever, tuberculosis, nervous disorders and liver disease. It is suggested to be a restorative agent for boosting mental capacities and to be beneficial for people with weakness and fatigue.
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Many pharmacological studies have been performed in laboratories and clinical trials have been performed on humans to investigate the effects of ginseng to substantiate these claims. However, many articles suggest that there is still no solid convincing evidence for ginseng having a significant beneficial effect [3].
Standardisation of ginseng extracts is now moving towards making products with a consistent amount of the reported active ingredients (ginsenosides). G115 is one such standardised form of ginseng with a total of 4% ginsenosides. The dosage of ginseng required for the reported health benefits is another source of confusion. Traditional practices typically use grams of ginseng in the decoctions whereas in western countries where ginseng is sold as a supplement, the dose of ginseng extract is much lower (milligrams).
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Chemicals in ginseng
Ginsenosides are thought to be the active constituents of ginseng extract. Some examples are shown in the box below:
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ginsenoside Rb1
ginsenoside Rd
ginsenoside Rg3
ginsenoside Re
ginsenoside Rg1
ginsenoside CK
ginsenoside Rh2
protopanaxadiol
What have we found?
Our research investigates these ginsenosides as purified chemicals to determine what their actions are on cells of the immune system. We have recently identified a P2X receptor on immune cells that some of the ginsenosides can interact with. This action seems to be restricted to ginsenosides belonging to the protopanaxadiol series and includes Rb1, Rd, Rg3, Rh2 and the major metabolite generated inside the body, ginsenoside CK.
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We recently published two articles (Dhuna et al, 2019 and Bidula et al, 2019) describing more of our findings about the action of ginsenosides on P2X receptors.
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First, we show that ginsenosides can also enhance the activity of P2X4 receptors which means that they are not selective for P2X7. Therefore, this might be something that is common to all P2X receptors and we are currently investigating this.
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Secondly, we have located the position of the binding pocket for the ginsenoside chemicals on the 3D P2X7 receptor structure. We used the most active compound (CK) and computer based modelling to identify a pocket which we have confirmed by mutating key amino acids within the P2X7 protein. The video shows the predicted binding location for CK on P2X7. As the structure rotates, it shows the trimeric nature of the P2X receptor. The 3 subunits are differently coloured. The molecules of ATP that activate the receptor are shown in red. As the blob-like structure transitions to a ribbon-like structure, the novel binding pocket which is inside the central part of the receptor, is revealed. We believe that the ginsenoside molecule travels into the centre of the receptor through the lateral portals (the three windows around the side) to dock into its pocket and help the channel to open.
Information sources
1. WHO Monographs on medicinal herbs volume 1 (http://apps.who.int/medicinedocs/en/d/Js2200e/19.html)
2. The Nature of ginseng by S Dharmananda (www.itmonline.org/arts/ginsengnature.htm)
3. Ginseng for cognition (review) Cochrane library (doi 10.1002/14651858.CD007769.pub2)
4. Pharmacology of ginsenosides; a literature review by Leung & Wong 2010 (doi: 10.1186/1749-8546-5-20)
5. The standardised G115 Panax ginseng C.A. Meyer extract A Review of its Properties and Usage by Scaglione et al
2005 (https://link.springer.com/article/10.2165/01197065-200502040-00003).
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