Botaceuticals

Immunity x Ginseng

These articles are not intended to provide treatment recommendations for the ongoing COVID-19 pandemic.
INTRODUCTION

Korean ginseng (Panax ginseng) is one of the most prized medicinal plants in the world. As a true icon of Asian culture, its root has been used there for millennia. Ginseng’s medicinal properties are so revered that they played a big part in the border being drawn between China and Korea. The Chinese Emperor believed the people of Korea plundered ginseng from the Manchurian forests and therefore decided to establish a precise border to be able to apply its harvest ban [1]. Even today, much research is being carried out on the therapeutic effects of this “root of a thousand virtues”: metabolic disorders, oncology..., including in the field of immunity [2-5].

Yet in Europe, ginseng is too often considered as a "general tonic". This largely cultural difference is intensified by the poor quality of ginseng used in Europe compared to premium products from Korea and Japan.

In the best of cases, European laboratories will ensure that the product is not adulterated and that it contains a high level of ginsenosides. However, as we will see later, not all ginsenosides are equal in terms of their benefits.

Ginseng’s main molecules of interest are numerous and can be categorized into 2 groups. There are others but their impact on the immune sphere does not seem crucial.

1. ACTIVE MOLECULES

1.1. Ginsenosides 

Ginsenosides are the main active molecules in ginseng. There is a wide variety, but they do not all share the same activity. Most of the ginsenosides found in ginseng are precursors of bioactive ginsenosides. These precursors are poorly assimilated by the body, although the intestinal microbiota converts a small proportion into bioactive form. So the dose of active ginsenosides entering the bloodstream is less than the dose of ginsenosides ingested.
Fortunately, the conversion into active ginsenosides is also possible outside the body. It is achieved via various methods of preparing ginseng, which range from traditional cooking and steaming to the most modern techniques.  For example, red ginseng is actually steamed white ginseng. Heat treatment serves to convert ginsenosides into bioactive form – just as the intestinal microbiota does. Black ginseng is cooked nine times to ramp up the level of bioactive ginsenosides. 
In Asia, some laboratories have developed sophisticated fermentation methods to boost active ginsenosides level.
Another method is optimizing molecular profiles by modulating growth conditions via vertical farming in a controlled environment. The molecular profile of a plant is defined by the conditions is faces during its existence: temperature, humidity, light, stress, nutrients etc 
Ginsenosides are found in the totum (full spectrum molecular profile) but require a significant culture time before being present in significant quantities. That’s why, in general, the longer you cultivate ginseng, the more potent it becomes. For example, most Asian ginseng is cultivated for at least six years.
Ginsenosides are also present in alcoholic extracts, which are conventionally used to concentrate them.

1.2. Ginsan

Recent studies on echinacea suggests much of its immunostimulatory activity derives not from the plant itself but the endophyte organisms colonizing it [1-5].  This preliminary data raises questions about plant function in the absence of these organisms; about the importance of the totum and preparation methods with fresh/dry plants, drying and steaming methods etc. 

2. GINSENG & IMMUNITY 

2.1. Ginseng & macrophages

The influence of ginseng compounds on macrophages is complex. Scientific publications number in the hundreds and explore a whole series of scenarios ranging from bacterial infection to cancer. However, we can extract three main actions of interest:

2.1.1. Optimization of phagocytosis

Ginseng seems to have the ability to optimize the efficiency of phagocytosis. Ginsenoside Rg3 [6-7] and ginsan [8-9] have been identified as promotors of the phagocytosis process and therefore the effectiveness of active macrophages. Note that this is an ‘optimization’ of active macrophages and not an increase in recruitment or a stimulating effect on the differentiation of macrophages.

2.1.2. A regulating effect on inflammation

Many ginsenosides have been shown to limit the inflammatory response. Ginsenosides Rg5 [10-11], Rk1 [11-12] and Rg3 [13-14] have been identified as active at this level. Data also exist for other ginseng extracts [15-16].
This observation suggests ginseng limits the immune response via fewer macrophages on-site. As we have seen for echinacea, this effect has the advantage of limiting the symptoms linked to excessive inflammation, while "staying the course".
It will be noted that in the case of ginseng, this positive impact has been reported in vivo, in particular in septisemia models, demonstrating that more ‘efficient"’ but gradually recruited macrophages lead to a better prognosis [17-21].

2.1.3. A tendency to favor the M2 phenotype

We saw in the first article (read HERE), that macrophages can present themselves under two phenotypes: M1, which actively secretes many pro-inflammatory cytokines and phagocytes and M2, which promotes the repair of tissues damaged by infections and trauma. Rg3 has been identified in multiple studies as favoring the M2 phenotype [22-24].
This activity confirms the regulatory potential of a ginseng rich in Rg3 and ginsan on innate immunity. It suggests a double-action on macrophages: limiting any phenomenon of deleterious inflammation on the one hand and promoting the effectiveness of the macrophages on the other.

2.2. Ginseng & dendritic cells

Several studies report a 2-fold influence of ginseng compounds on dendritic cell activity. 

2.2.1. Stimulation of dendritic cell activity

Firstly, activation of dendritic cells – immune system stimulating antigens – has been observed with various ginseng molecules, in particular, ginsan [25-26]. Rg3 plays a role as well, although the model is more associated with immunity to cancer cells than to an infection [27]. This activation can have various consequences downstream where Rg3 has been shown to have influence.

2.2.2. Modulation of dendritic cell activity

If ginsan acts as the primary activator of dendritic cells, then bioactive ginsenosides and in particular, Rg3, have been shown to limit the activation of certain types of T lymphocytes by these same dendritic cells [28-29]. In other words, the dendritic cells are activated but perform specific ‘tasks’.

2.3. Ginseng & lymphocytes


So certain ginsenosides limit the activation of certain types of T lymphocytes: Th1 [29], Th2 [30] & Th17 [28] by modulating the activity of dendritic cells. Conversely, they will promote the activity of Treg lymphocytes [31-33]. 
Tregs are T lymphocytes that act to avoid autoimmune reactions. They prevent cytotoxic T lymphocytes from recognizing antigens specific to the body and do not attack ‘the self’. They are little diplomats of the immune system. 
One might wonder how Treg stimulation promotes natural defences. In reality, it has been shown that Tregs play a positive role in natural defences. By limiting the action of T lymphocytes, they allow them to focus on important antigens [34]. 
Beyond the direct effect on immunity, this type of influence suggests that ginsenosides should also limit the production of IgE (Immunoglobulin E) by B lymphocytes in favor of IgA, which is confirmed by the literature [35- 36]. It is interesting to note that this Treg & IgA activation cascade is reminiscent of the health-benefiting interactions between the immune system and the intestinal microbiota.

2.4. Ginseng & natural killer (NK) cells 

Ginseng also appears to have an activating effect on NK cells, through some of its constituents [37-40]. This aspect arouses the interest of researchers in an oncological context. The activation of NK cells is obviously interesting in the context of an intracellular infection: viruses, intracellular bacteria etc

2.5. Antiviral activity 

Beyond its direct effects on immunity, ginseng exhibits antiviral properties that indirectly strengthen immunostimulatory activity [41-44]. While this is not the most prominent property of ginseng, it remains of great interest.

3. TOMORROW'S TRACKS

3.1. What type of extract?

As we saw in the introduction, two aspects must be considered when selecting an effective ginseng.

    • The concentration of Rg3 and Rg5:

A ginseng rich in ginsenosides will obviously be more effective than a ginseng containing hardly containing any, but conventional ginsenosides remain little bioavailable and their exhibit limited bioactivity. is very limited.

Quality ginseng products will be able to give you define the rate ratio of each ginsenoside. This will allow you to compare the levels of Rg3, Rg5 and Rk1 and therefore identify a really active truly potent ginseng.

    • The presence of ginsan:

Although they appear secondary in certain areas, ginsan play a significant role in the immune potential of ginseng. These polysaccharides are conventionally more abundant in cooked ginseng (red or black ginseng) but are unfortunately only very slightly soluble in alcohol. The totum is therefore very important in the context of immune health.

Obviously, the ideal is ginseng that is both rich in rare ginsenosides and ginsan. Nevertheless, this type of product is scarce and its elevated price will only be suitable for formulas that aim for excellence. That said, we could also consider that it is better to integrate 100 mg of bioactive ginseng than 500 mg of non-assimilable ginseng.

3.2. For which product?


Based on the above data, the potential of ginseng to favorably influence immune function is more than significant and seems suitable for all types of products. However, its global action leans to its use in a preventive context. Some studies also show that while bioavailable ginsenosides can act quickly, the positive impact of ginsan evolves positively week after week [45].

While the data shows ginseng can be effective in prevention, we reiterate the evidence for direct treatment is much more speculative.

3.3. What to associate it with?


3.3.1. For a product in winter.

As we have seen, ginseng rich in bioactive ginsenosides has a global impact on natural defences. As part of the development of a ‘winter boost’ formula, we can thus reinforce the two additional pillars: anti-infectious activity and regulation of inflammation. The purely immunomodulating aspect being largely taken into consideration by ginseng itself.

In aromatherapy, we can associate an oil rich in 1,8-cineole for its inflammatory regulating properties and its antiviral activity.

We can also consider adding marjoram oil in capsule form (Origanum majorana) to reinforce the anti-infectious activity.

Finally, fans of more ‘complex’ formulas will consider adding essential turmeric oil (Curcuma longa) rich in aromatic turmerone. This essential oil with properties too often confused with turmeric extract (the essential oil does not contain curcumin), is of great interest in many health spheres. Noted for neuroprotective and anti-inflammatory skin benefits, this essential oil is also immunomodulating [46-49].

Provided that the two ingredients are of premium quality, the duo ginseng + skullcap (Scutellaria baicalensis) represents an almost ideal solution to boost the defences in winter when it comes to herbal medicine. Indeed, the skullcap of Lake Baikal has a very significant antiviral activity [50-55] and inflammation regulatory properties [56-60]. Combined, these two plants address almost all of the relevant aspects of immunity. Only a probiotic could complement this tandem even more.

3.3.2. For a global approach to daily immune health.

Science shows ginseng is an excellent global solution for daily immune health. Beyond its immunostimulatory and immunoregulatory properties, a ginseng rich in Rg3, Rg5, and Rk1 is also active in metabolic balance (glycemia, lipid metabolism, and cardiovascular health) or neuroprotection (neuroprotective and nootropic).

These actions can occur alone or in advanced formulas that may include other ingredients active in other spheres, like the intestinal microbiota.
In aromatherapy, we can consider combining it with an oil-rich in geraniol such as the palmarosa (Cymbopogon martinii) or the monard or wild bergamot (Monarda fistulosa) whose beneficial properties on the intestinal microbiota have been highlighted.

Essential oils rich in citral can also be considered in this context [61].

In phytotherapy, a source of chlorogenic acids such as green coffee (Coffea canephora), artichoke (Cynara scolymus), or blueberry leaf (Vaccinium myrtillus), should promote the balance of the microbiota.

Finally, it is worth noting that the positive impact on Tregs and the production of IgA suggests formulations with probiotics could prove to be particularly relevant.

CONCLUSION

Korean ginseng (Panax ginseng) is one of the most suitable herbal medicines for maintaining optimal immune health. Scientific backing is strong provided the root is rich in active molecules: ginsenosides Rg3, Rg5 and Rk1 and even acidic polysaccharides like Ginsan.

It is a shame quality issues mean the European market rarely benefits from formulas that take advantage of its countless virtues. This situation, thankfully, is changing as manufacturers step up in the pandemic climate we find ourselves in.

Want to know more about ginseng and their bioactive components? Check these two articles which dive deep into rare ginsenosides and the health areas where they have most impact:
  1. Ginsenosides Rg3 - HERE
  2. The duo Rg5: Rk1 - HERE
Do not hesitate to contact us if you have additional questions at info@botalys.com

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