Glabridin

Glabridin is one of the main lipid-soluble plant constituents of licorice root. It belongs to the isoflavan chemical family and was identified in 1976 [1]. Glycyrrhizin, the water-soluble and sweet constituent of the root, is a different substance. Both come from the same plant, but they do not occur in the same product. Cosmetic manufacturers buy glabridin for skin brightening products [2]. In supplements, the same lipophilic flavonoid fraction is sold as a solution in oil [3]. Glabridin is also reported as a species-specific constituent of Glycyrrhiza glabra. It is not expected in the other two commercial species [4].

How much is present in licorice root?

Which licorice first? Three Glycyrrhiza species circulate in commerce. In 117 licorice samples verified with four genetic markers, species-specific constituents were identified. Glabridin was specific to G. glabra, licochalcone A to G. inflata, and glycycoumarin to G. uralensis. Only 6% of the samples and hybrids fell outside this rule [4]. The name "licorice root extract" alone does not guarantee glabridin. A marker means a constituent that distinguishes the species.

In roots and underground shoots, in small amounts. In an extraction using an ethanol-water mixture, a Chinese licorice sample yielded 0.92 g glabridin and 2.4 g glycyrrhizin per kilogram. The study did not report the species [5]. Another study obtained 16 mg of glabridin with over 95% purity from 10 g of licorice root [6].

The proportion in the extract depends on the method. In the same study, the glabridin content of the crude extract was 0.2%. It rose to 35.2% after solid-phase separation [6]. Glabridin was measured at 3.9% in one licorice extract [7]. In a crude extract, glabridin was the most abundant constituent at 11.6% [8]. The amount is understood from analytical measurement, not from the plant name.

What comes along with it. The same lipophilic fraction also yields hispaglabridin A, hispaglabridin B, 4'-O-methylglabridin, isoliquiritigenin, and formononetin [8]. Glabrene also belongs to the same root [9].

Glabridin, glycyrrhizin, glabrene: what is the difference?

Values are taken from PubChem. Glycyrrhizin also appears on the market as glycyrrhizic acid; both are the same substance. XLogP shows whether a substance prefers oil or water. Higher values indicate higher lipophilicity. Glabridin is on the lipid side at 3.9. Kojic acid is on the water side at -0.9. The XLogP value of glycyrrhizin also appears high. However, the molecule carries two sugars and dissolves in water. A single number is not always sufficient.

Glabrene is a desirable line item on a certificate. It is a close relative from the same root as glabridin. The inhibitory potency on tyrosinase was measured at 3.5 µmol/L for glabrene and 8.1 µmol/L for isoliquiritigenin [9]. In the same study, the extract effect was higher than expected from its glabridin content alone [9]. Extract performance cannot be predicted from a single constituent ratio.

The sweet one is not glabridin. Glycyrrhizin provides the sweet taste of licorice root and its known blood pressure effect. In sensitive individuals, 100 mg/day of glycyrrhizin is sufficient to trigger this effect. Authors consider 10 mg/day a safe intake for most healthy adults [10]. For this reason, the origin fraction of the product is verified on the certificate.

What is it used for?

Skin brightening, cosmetics. Glabridin reduced tyrosinase activity in murine melanoma cells between 0.1 and 1.0 µg/mL. In the same study, applying 0.5% glabridin to guinea pig skin suppressed UVB-induced pigmentation and erythema [2]. The measured inhibitory potency on the enzyme was 0.25 µg/mL, approximately 0.77 µmol/L [11].

Tyrosinase measurements vary by the enzyme used. In a screening of 50,000 compounds against human tyrosinase, kojic acid remained above 500 µmol/L. Arbutin and hydroquinone remained at millimolar levels [12]. When comparing an inhibition value with another substance, the enzyme source must be checked.

In humans. A gel containing glabridin, andrographolide, and apolactoferrin was applied twice daily for six months in 40 women. Melasma severity scores improved significantly compared to baseline [13]. Melasma refers to symmetrical dark patches on the face. A 2.1% cream containing resorcinol, arbutin, and licorice root extract was compared with hydroquinone cream in 20 women each over 12 weeks. Skin brightness was reported at 93% and 89%, respectively [14].

Soothing and UV. Glabridin reduced inflammatory markers at the cellular level [2]. Liposomal glabridin reduced erythema and skin thickening in UVB-exposed skin. It also decreased the expression of pro-inflammatory signaling molecules [15].

Oral care. Glabridin and licoricidin reduced the growth, adherence, and acid production of Streptococcus mutans, a bacterium linked to dental caries. Toxicity to oral cells was low or absent at tested concentrations [16]. Minimum inhibitory concentrations of pure licorice markers were measured at 12.5 to 25 µg/mL [17].

Supplements form a separate product category. Licorice flavonoids dissolved in triglyceride oil were tested in healthy volunteers at doses of 300, 600, and 1,200 mg per day. The single-dose study was conducted with five men. Glabridin reached peak plasma concentration in about 4 hours, with an elimination half-life of about 10 hours. No noteworthy changes appeared in blood counts or clinical chemistry after four weeks of use [3]. In mice fed a high-fat diet, a glabridin-rich supercritical CO₂ extract reduced weight gain in a dose-dependent manner [18]. In 10 subjects taking 100 mg of licorice daily for two weeks, isolated plasma LDL particles were more resistant to oxidation compared to baseline [19].

Safety data. In a 90-day rat study with an oil solution containing 2.9% glabridin, the no-observed-adverse-effect level was 800 mg/kg/day in females and about 400 mg/kg/day in males. The same study noted an anticoagulant effect in both sexes [20]. Genotoxicity assays of the same solution yielded negative results in bacterial and rat tests. Damage was observed only above 0.6 mg/mL in a cellular assay with an added liver enzyme mix [21].

Oral absorption of glabridin is low. Bioavailability is the fraction of an oral dose reaching systemic circulation. It was reported as 7.5% [22] and 6.6% [23] in rats. The second study measured the hepatic first-pass loss at 62% [23]. Glabridin is a substrate for an intestinal efflux transporter, which limits its absorption [22].

4% or 35%: which form?

The choice depends on five questions.

• Which species? Glabridin is a species-specific marker for G. glabra [4]. If the species is unknown, the content is also unknown.
• Which fraction? Solvents of intermediate polarity, such as ethanol-water mixtures, extract both constituents [5]. Separation requires an additional purification step [6]. In a study extracting glycyrrhizin with supercritical CO₂, a binary modifier was used [25].
• Extract or diluted solution? Is the percentage based on the neat extract or the total carrier solution? In dietary supplements, an example of this format is a solution in triglyceride oil, containing 2.9% glabridin in the concentrate [20].
• How much is needed? The effective topical application on guinea pig skin was 0.5% glabridin [2]. For a 100 kg batch of serum targeting this level, 500 g of glabridin is required. That corresponds to 12.8 kg of a 3.9% extract or 1.4 kg of a 35.2% extract. These figures are examples. In clinical trials, total active levels are much lower; one benchmark cream contained 2.1% total actives [14]. Target levels depend on the product type.
• Price. Compare the price per kilogram of glabridin, not per kilogram of extract. The 9-fold difference in usage rate between the two extracts above appears in this calculation.

Why licorice when hydroquinone, arbutin, and kojic acid exist? Hydroquinone was the reference substance in this field for a long time. When regulators in Japan, Europe, and the United States questioned its safety, the search for alternatives began. Retinoids, azelaic acid, arbutin, kojic acid, ascorbic acid, and licorice root extract are options named in this search [26]. Licorice offers two differences.

First is the companion compounds. The inhibitory effect of licorice extract on tyrosinase exceeded the expected level from its glabridin content alone. The same study reported that glabrene and isoliquiritigenin also inhibit the enzyme, with potencies of 3.5 and 8.1 µmol/L [9]. A research group working on G. uralensis found that glyasperin C was more potent than glabridin [11]. An extract provides these constituents together. A single synthesized substance lacks this co-occurrence.

Second is the label. The botanical name is recognized by consumers and appears accordingly on the label.

How to read the Certificate of Analysis?

Method. Glabridin is measured by liquid chromatography (HPLC, a method separating a mixture into components and quantifying each). When the same extract was measured by two separate methods, results were 3.9% and 3.8%. The difference was not significant [7]. The certificate should state the analytical method.

Glabridin, glycyrrhizin, and total flavonoids are separate lines. Validated methods exist to quantify all three simultaneously [27]. The "total flavonoids" value is not the glabridin value. A high total flavonoid content can coexist with low glabridin.

Species questions are resolved by analysis. A mass spectrometry method quantifying 14 licorice constituents simultaneously identifies glabridin alongside markers for the other two species (glycycoumarin, licochalcone A, licoricidin). The method differentiated root powder, extracts, and complex supplements [24]. If a product reports both high glabridin and high licochalcone A, an explanation is required.

The glycyrrhizin line. It shows which fraction the product originates from. For oral products, the exact quantity is especially relevant [10].

Specification and result are different things. A specification is the manufacturer commitment. The measured value is the result for that specific lot. The technical data sheet (TDS) is a general document. The certificate of analysis (CoA) belongs to the lot.

What indicates quality?

Species identity. The marker compound and botanical species are verified together [4] [24]. A document stating only the plant name does not resolve this question.

Identity of the fraction. Intermediate polarity solvents extract both glycyrrhizin and glabridin together [5]. Separation requires an additional purification step [6]. For this reason, both lines on the certificate should be read together.

Solvent residue. Residual levels depend on the extraction solvent. Licorice root extractions in the literature use ethanol, ethyl acetate, and supercritical CO₂ [5] [6] [18]. The solvent used and its residual limits should be confirmed.

Raw material testing. Botanical raw materials must also be tested for pesticides, mycotoxins, and heavy metals.

How does it behave in formulations?

Insoluble in water. The XLogP value of glabridin is 3.9. The main challenge in practical use is poor water solubility. Loading glabridin onto porous silica particles increased its aqueous solubility more than 4-fold [28]. It does not disperse directly into aqueous systems and requires a carrier.

Skin penetration varies with the carrier. In a nanoemulsion based on a menthol and camphor mixture, skin permeation of glabridin was measured at 28.3 µg/cm². The same study found 9.9 µg/cm² with an isopropyl myristate phase and 3.8 µg/cm² with a simple solution [29]. Nanosuspensions also improved penetration compared to coarse suspensions [30]. Published formulations rely on carriers such as liposomes [15], nanoemulsions [29], nanosuspensions [30], and porous silica [28].

Storage. A nanosuspension showed 5.5% active ingredient loss over three months at room temperature [30]. The longest stable storage for silica-loaded samples was measured at 7 months [28]. Storage conditions are defined in the manufacturer documentation.

Use levels. Published studies apply a wide range of concentrations to the skin. An animal study used 0.5% pure glabridin [2]. A benchmark cream tested in humans contained 2.1% total active ingredients across three compounds [14].

Safety and labeling. Follow the safety data sheet (SDS) when handling the extract. In cosmetics, the label name is the INCI name. Whether a single constituent percentage may be declared on an extract label depends on product classification and current regulations. Confirm product compliance using manufacturer documentation.