Botaceuticals

Immunity x Echinacea

These articles are not intended to provide treatment recommendations for the ongoing epidemic.
INTRODUCTION

Panax Ginseng is the “ultimate” reference immunostimulant in the Orient, whereas Western cultures have focused on Echinacea (Echinacea purpurea or Echinacea Angustifolia).

This pearl of Western phytotherapy is a plant of the Asteraceae family with flowers that resemble the daisy and whose heart is remarkable prominent. Moreover, it looks like a sea urchin, which gave the name to the plant: the name Echinacea comes from "echinos", meaning sea urchin in ancient Greek.
The root of the plant is particularly appreciated in a medical context, although sometimes they use the whole plant in the production of alcoholic extracts (mother tinctures). A choice that may have consequences on the molecular profile of the extract and thus on its properties.

1. ECHINACEA’S MAIN MOLECULES OF INTEREST  

1.1. Alkylamides

  • considered to be the key molecules of Echinacea
  • lipophilic molecules with good bioavailability and many properties
  • present in all parts of the plant but more abundant in the root
  • present in alcoholic extracts

1.2. Polysaccharides

  • large sugar assemblies 
  • often identified as having an impact on the intestinal microbiota and immunostimulatory
  • mainly present in the roots
  • not very soluble in ethanol, therefore mother tinctures and other extracts of the same type are rarely rich in polysaccharides 
  • present in the powdered plant or certain aqueous extracts

1.3. Phenolic compounds

  • Echinacea contains numerous phenolic compounds as do other medicinal plants
  • the most interesting are caffeic acid derivatives such as echinacoside or chicoric acid
  • present in the roots and aerial parts of the plant
  • could potentially be interesting under certain conditions, for example: potentially superior antiviral activity

2. BEYOND THE MOLECULES OF THE PLANT 

Some recent data seem to support an original theory explaining that a good part of the immunostimulatory activity of Echinacea is not due to the plant itself but to the endophyte organisms which colonize it [1-5].

It seems too early to determine how crucial the role of these organisms is. However, the results raise the question of the effectiveness of the plant in the absence of these organisms. If this hypothesis were to be confirmed, it would give crucial importance to the "totum" but also to the methods of preparation: fresh/dry plant, drying methods, ...

3. ECHINACEA & IMMUNITY 

The traditional allegation of strengthening natural defenses are no longer a subject of discussion since the European Medicines Agency recognizes the scientific credibility of this application [6]. However, the mechanisms underlying this property are a real Gordian knot. Indeed, a complete review of the bibliography on the properties of Echinacea and its active substances inevitably leads to contradictions that can be explained by the nature of the extracts tested. 

3.1. Echinacea & Macrophages

The available data on the immunomodulatory properties of Echinacea are numerous [7]. Most of them refer to the influence on innate immunity, on macrophages in particular. Nevertheless, these data may appear contradictory, depending on the type of extract used.  Extracts rich in polysaccharide fraction generally tend to stimulate the activation of macrophages [8-11], while extracts rich in alkylamides tend to limit the inflammatory response [12-19].  

A limitation of inflammation can seem contrary to immune defenses: less recruitment on the site of infection. Nevertheless, it allows limiting the extent of the symptoms linked to this response and "maintain the defenses" over time. An example is nasal congestion.

When it comes to phenolic compounds, we observe variations according to their nature. However, we mainly find anti-inflammatory properties, especially with cynarine. They are not necessarily linked to macrophages but they reinforce the overall effect [20-22]. Note that the direct antiviral effect of Echinacea is probably linked to these molecules. Therefore, the "richness" in phenolic acids should not be overlooked.

Does this mean that using a totum could lead to "properties that cancel each other out"? Not necessarily. Polysaccharides can play a positive role at various levels and in particular, with the intestinal microbiota like many polysaccharides. While alkylamides, by their bioavailability, play on inflammatory sites.

Whole plant extracts are not necessarily less efficient. Their diversity in phenolic compounds could well have a positive impact on antibacterial/antiviral activity and/or on the intestinal microbiota in the long term. On the other hand, it is difficult to have an extract that is simultaneously rich in alkylamides, in phenolic compounds and in polysaccharides. To choose is to give up.

3.2. Echinacea & other immune actors

Some studies report a positive activity on the activation of other cell types, in particular via chicoric acid, which has been identified as an activator of dendritic cells [23] and T-lymphocytes [24].

The data relating to Echinacea properties focus mainly on inflammation or its consequences. In particular, the anti-inflammatory dimension of alkylamide-rich extracts and the immunostimulatory properties of polysaccharides-rich extracts [25-27]. Therefore, the activity of Echinacea seems to focus on the first line of defense: innate immunity. This happens by stimulating immunity with certain active ingredients or by limiting inflammatory mechanisms with others.

3.3. And at molecular level?

At the molecular level, we find this duality between polysaccharides, which stimulate the production of molecules activating immunity and alkylamides, which promote the control of inflammation. Alkylamides do that in particular by stimulating IL-10 and inhibiting pro-inflammatory molecules [28-29]. Observations at the molecular level seem to validate the effects identified at the cellular level.

Note that certain alkylamides have been identified as agonists of the CB2 receptors responsible for the stimulation of the endocannabinoid pathways particularly present in the immune cells [30-32]. This activity is anything but trivial because it could, next to its effect on the macrophage, intervene with certain categories of lymphocytes and especially stimulate Tregs.

Treg stimulation is often associated with a form of immune system tolerance. However, there is some evidence to suggest that when T cells are more tolerant, they also tend to be more effective because they focus on high-level antigens affinity [33]. It may not be impossible that this aspect is linked to the relationships between the body and its microbiota.

Finally, the impact on PPARs is a track that might be worth further investigation [34]. Note that the connections between CB2 and PPAR are highlighted for other plant extracts that are considered to be immunomodulatory (Ginseng, Beta-caryophyllene...). This double action is explained by the fact that endocannabinoids (molecules of the body) have this double activity too.

For the record, cannabidiol (CBD) from cannabis (Cannabis sativa) is an antagonist of CB2 receptors and can therefore reduce the effects of Echinacea.

4. TOMORROW'S TRACKS

4.1. What type of extract?

oot or whole plant? Totum or alcoholic extract? It is difficult to decide because each type of extract has advantages in terms of active molecules. Some preparations are likely to be more abundant in molecular type than others.

For the richness in alkylamides:

An alcoholic extract of the roots contains more alkylamides than an alcoholic extract of the whole plant. However, the diversity of alkylamides is greater with the whole plant.

For the richness in polysaccharides:

An enriched aqueous extract contains more polysaccharides because they are poorly soluble in alcohol. Polysaccharides are mainly present in the roots.

For phenolic compounds:

Phenolic compounds are present in the root as well as in the aerial parts but in different proportions depending on the molecules. The exclusive intake of the root brings less "phenolic variety".

It is essential to understand that these are generalities. We can have a root extract very poor in alkylamides and an extract of the whole plant that contains much more. In the end, the molecular specifications of the ingredient will decide.

4.2. For which product?

The data described above tend to highlight an advantage of Echinacea. On one hand, it stimulates the defenses by stimulating the immune system and on the other hand it limits the impact of an infection by acting anti-inflammatory and anti-infective.

Therefore, we have an ingredient that has its place in a product intended for the "treatment" of winter ailments. In other words, when the person presents the first symptoms of a cold or when he/she suffers from recurrent infections in midwinter period.

Echinacea is slightly less suitable as a preventive product for daily "immune" health since global support requires a more integrative approach.

4.3. What to associate it with?

Echinacea is intended for a formula that supports a person with a cold.  It would preferably be associated with ingredients that control of inflammatory symptoms and indirect support the immune system by antibacterial and/or antiviral action. 

In Aromatherapy, we use essential oils rich in 1,8-cineole to limit the symptoms, possibly accompanied by oils rich in carvacrol/thymol for their powerful anti-infectious properties. 

In phytotherapy, we can turn to the great classics that are Cape Geranium (Pelargonium sidoides) or Elderberry (Sambucus nigra).

For a formula intended for prevention over a limited period:

In Aromatherapy, an essential oil rich in 1,8-cineole is always justified in delicate periods. However, we should limit the dose of essential oils rich in carvacrol/thymol to prevent the disturbance of intestinal microbiota.

Also, we should consider essential oil of Clove (Eugenia caryophyllus / Syzygium aromaticum) that is rich in eugenol. The stimulating properties of eugenol on humoral immunity, namely the production of antibodies, have been demonstrated in various studies [35-37].

We can consider providing antiviral and immunostimulatory activity too. Purists would probably think of the Tea tree (Melaleuca alternifolia), but we could easily prefer marjoram (Origanum majorana).

In herbal medicine, we can opt for Lake Baikal skullcap (Scutellaria baicalensis) with powerful antiviral properties when it is rich in baicalin [38-43]. This active compound is a regulator of inflammation [44-48] and has positive effects on the microbiota intestinal [49].

If we do not have a quality supply (extremely rare), we can replace it with an extract rich in ursolic/oleanolic acids [50-53], like certain extracts of trilobed sage (Salvia triloba) or marjoram (Origanum majorana).

Finally, a ginseng (Panax ginseng) rich in bioactive ginsenosides (Rg3, Rg5, Rk1) as well as ginsan (polysaccharides present in the total but not in the alcoholic extracts) provides an excellent formula. This type of ginseng presents a myriad of properties regarding the immune sphere (see the following article).

CONCLUSION

Behind its appearance as "grandmother's remedy", Echinacea is a medicinal plant in all its splendor, showing off its many properties as well as its great molecular complexity.

It is possible to express a favorable opinion to this plant in the context of "winter ailments". It can be considered single or combined with other active ingredients for the development of more specialized products.

Nevertheless, in the case of a preventive formula intended to ensure optimal "immune health" and not to counter the beginnings of a little "winter disorder", we prefer its oriental alter ego whose regulatory effect on the immunity seems more suitable (see next article).

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