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Principal indication: very reactive, irritated skin, redness
A43 and A46

Bibliographical summary
  • Molecule more than 98% pure, extracted from Liquorice root
    (Glycyrrhiza glabra L.)

One of the major actives in liquorice is glycyrrhizin, which is hydrolyzed into two glucuronic acids and the corresponding aglycone, glycyrrhetinic acid. Glycyrrhetinic acid is formed by an oleanane skeleton carrying a carboxylic function at C30 and an cetone, established at C11. This molecule is not naturally present in the body. Only the 18 isomer of glycyrrhetinic acid, also called enoxolone, is active and known for its anti-inflammatory properties. Locally applied, glycyrrhetinic acid is used principally in the symptomatic treatment of moderate and not superinfected inflammatory incidents such as atopic eczema, solar erythema, seborrhaeic dermatitis, pruritis vulvae or insect stings.

The history of liquorice dates back several centuries. It was already mentioned in Chinese treatises on traditional herbalism and in the papyrus scrolls of ancient Egypt. In traditional Chinese medicine, liquorice root, called “Gan Cao”, is commonly used as an energy tonic to treat problems caused by "Qi" or energy deficiency. Its aroma improves the taste of all preparations. Moreover, liquorice slows down and extends the effects of strong tonic potions. It is often prescribed in Chinese medicine for its fortifying, high-calorie virtues. Indeed, it is capable of cancelling out the effect of certain poisons (poisonous mushrooms, belladonna…). It is also known for its soothing properties.

Theophrastus, a disciple of Aristotle and the "father" of botany, wrote in his Historia plantarum that the "Scythian root" (liquorice) has the ability to quench the thirst of anyone who keeps it in his mouth. We can note, for example, that the armies of Alexander the Great are thought to have overcome periods of water shortage during their long campaigns thanks to this plant.


Glycyrrhetinic acid has anti-inflammatory properties. It is involved in the oxidation of cortisol (hydrocortisone) into cortisone, in the synthesis and release of histamine and in the increase in the intracellular calcium concentration induced by an antigen.

The skin has the ability to oxidize cortisol (glucocorticoid inhibitor in the various stages of the inflammatory response) into cortisone, which is its inactive form. The enzymes that catalyze this reaction are: 11 hydroxysteroid dehydrogenase type 2 (11HSD), 5-reductase and 3 hydroxysteroid dehydrogenase (3 α HSD).

• Enoxolone prevents the cortisol-cortisone conversion
18 glycyrrhetinic acid has corticoid-mimetic properties in preventing the cortisol-cortisone conversion.
Indeed, this acid inhibits 11 HSD, 3 HSD and 5-reductase [1]. The inhibition of 5-reductase brings about a slow down in the elimination of steroids and an extension of their plasma half-life [1].
The increase of the cortisol/cortisone ratio stops the synthesis and release of cytokines involved in the inflammatory reaction process and, in particular, in the vasodilation or contraction of non-vascular smooth muscles.

• Enoxolone blocks histamine synthesis
Glycyrrhetinic acid is also involved in the synthesis and release of histamine. When skin cells are attacked by ultra-violet rays, the immune system takes over to repel them. The mastocytes and polynuclear basophils are alerted and trigger the release of histamine. This chemical mediator diffuses until it reaches the blood vessels. A powerful vasodilator, histamine is responsible for the red colour of the skin and the sensation of heat. 18 glycyrrhetinic acid blocks histamine synthesis by inhibiting the histidine decarboxylase [2,3] and its release by inhibiting the increase in the intracellular calcium concentration [2, 3].

• Enoxolone soothes the skin
These different elements explain the anti-inflammatory properties of glycyrrhetinic acid. In vivo, its effectiveness has been demonstrated on patients suffering from atopic dermatitis. Indeed, application of a 2% liquorice gel for two weeks brings about a significant reduction in erythema, oedema and itching. Moreover, PO12 cream composed of 2% glycyrrhetinic acid is proposed as a skin protector and indicated in self-medication for the local treatment of moderate skin irritations [4]. Finally, glycyrrhetinic acid has shown its effectiveness (in combination with hyaluronic acid, a vitis vinifera and telmesteine extract) in preventing and limiting skin reactions caused by radiotherapy with an alleviation of burning sensations, erythemas and dermatitis [5, 6].

A major, and particularly interesting, natural active, with a corticoid "mimetic" structure, it has a well established profile and activity level. Skin inflammations do not respond, or respond badly, to the anti-inflammatories used in other fields (acting essentially on the lipoxygenase pathway). Glycyrrhetinic acid, using a specific mechanism, has an activity related and a level comparable to hydrocortisone (when topically applied), a first-generation corticoid, well defined in its harmlessness dermally (no systemic repercussions) whose activity, although modest compared with modern glucocorticoids, is significant and useful wherever one fears the lack of control of repeated applications and the concomitant risks.
At 2%, we can consider that the activity of 18G is comparable to 1% hydrocortisone, insofar as the formula uses pro-penetrants and will show itself to be effective on irritations, redness, itching caused by skin inflammations (slight eczema, insect stings, solar erythema, razor burn, slight allergic sensitivity…). It will be beneficial to combine it with 1% hydrocortisone, which it can synergize, or other soothing agents with a different mechanism or activity (overall symptomatic weaker) like bisabolol, allantoin or oat extracts. There is no reason to believe that higher concentrations may yield better results. Although the safety profile is satisfactory, concentration at 2% may, out of prudence, be limited in its use over time (acute, a few days to a few weeks).
At 0.7%, the dose recommended by cosmetics regulations, activity is very limited and often barely demonstrable on acute inflammations. Pro-penetrants and a suitable formulation (particularly in combinations) may confer an interest on effects limiting cutaneous sensitivity (sun with vitamin E, reactive skin with good skin conditioners, etc.).
At this concentration, the safety margin on long-term use seems more satisfactory to toxicological experts.
Exposure to UVs induces chemical and biological reactions. Sunburn, also called UV-induced or solar erythema, is characterized by painful blistering and sometimes second degree burns. Sunburn causes the release of inflammation mediators into the tissues. The first stage of the inflammation manifests as a more, or less, painful redness, which disappears on pressure, demonstrating that it is related to the dilation of the superficial blood vessels in the skin.
These elements show the interest of glycyrrhetinic acid as an anti-inflammatory agent. It is useful in treating UV-induced erythemas, burning sensations and sensations of heat. Moreover, the final report on the safety assessment of glycyrrhetinic acid shows that its use in cosmetics compositions presents no danger at a concentration of 2% [7].


The body of publications and scientific studies, customary usages of this active and our expert's opinion concur in using Enoxolone pure Active at the dose of 280 mg per bottle (for the face) and 930 mg per bottle (for the body).



[1] Actifs et additifs en cosmétologie. Martini MC et Seiller M. 3ème édition. p 633-634. 2006
[2] Effects of glycyrrhizin and glycyrrhetinic acid on dexamethasone-induced changes in histamine synthesis of mouse mastocytoma P-815 cells and in histamine release from rat peritoneal mast cells. Imanishi N et al., Biochem Pharmacol. 38(15):2521-6. 1989.
[3] Inhibition of histamine synthesis by glycyrrhetinic acid in mast cells cocultured with Swiss 3T3 fibroblasts. Lee YM et al., Int Arch Allergy Immunol. 110(3):272-7. 1996.
[4] VIDAL p.1640
[5] A double-blind, randomised, vehicle-controlled clinical study to evaluate the efficacy of MAS065D in limiting the effects of radiation on the skin: interim analysis. Leonardi MC et al., Eur J Dermatol. 18(3):317-21. 2008
[6] A double-blind, vehicle-controlled clinical study to evaluate the efficacy of MAS065D (XClair), a hyaluronic acid-based formulation, in the management of radiation-induced dermatitis. Primavera G et al., Cutan Ocul Toxicol. 25(3):165-71. 2006.
[7] Final Report on the Safety Assessment of Glycyrrhetinic Acid, Potassium Glycyrrhetinate, Disodium Succinoyl Glycyrrhetinate, Glyceryl Glycyrrhetinate, Glycyrrhetinyl Stearate, Stearyl Glycyrrhetinate, Glycyrrhizic Acid, Ammonium Glycyrrhizate, Dipotassium Glycyrrhizate, Disodium Glycyrrhizate, Trisodium Glycyrrhizate, Methyl Glycyrrhizate, and Potassium Glycyrrhizinate. F.A. Andersen. International Journal of Toxicology. 26(2): 79-112. 2007

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