Glabridin

Glabridin at a Glance

Glabridin is a prenylated isoflavan — an isoflavonoid — and the signature lipophilic flavonoid of licorice root (Glycyrrhiza glabra). It is the principal component of the root’s hydrophobic “licorice flavonoid oil” and effectively marks the species: it is abundant in G. glabra but largely absent from Chinese licorice (G. uralensis), making it a chemotype fingerprint ^{18Reference 18Wahab S et al. · 2021ReviewGlycyrrhiza glabra (licorice): a comprehensive review on its phytochemistry, biological activities, clinical evidence and toxicologyView study →}.

Its headline role is cosmetic. Glabridin is a potent tyrosinase inhibitor, and this underlies its biggest commercial use by far — as a skin-lightening / anti-hyperpigmentation active in topical cosmeceuticals ^{1,2Reference 1Yokota T et al. · 1998The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammationView study →Reference 2Chen J et al. · 2016Inhibitory mechanisms of glabridin on tyrosinaseView study →}. Around that sit a cluster of mostly preclinical activities: anti-inflammatory (TLR4/NF-κB), antioxidant (protecting LDL from oxidation), phytoestrogenic (it binds the human estrogen receptor), metabolic (AMPK/GLUT4 glucose uptake) and serotonergic (in-vitro serotonin-reuptake inhibition) ^{4,5,7,9,11,21Reference 4Ofir R et al. · 2003Inhibition of serotonin re-uptake by licorice constituentsView study →Reference 5Tamir S et al. · 2000Estrogenic and antiproliferative properties of glabridin from licorice in human breast cancer cellsView study →Reference 7Chang J et al. · 2021Glabridin attenuates atopic dermatitis progression through downregulating the TLR4/MyD88/NF-κB signaling pathwayView study →Reference 9Sawada K et al. · 2014Glabridin induces glucose uptake via the AMP-activated protein kinase pathway in muscle cellsView study →Reference 11Kang MR et al. · 2015Cardiovascular protective effect of glabridin: implications in LDL oxidation and inflammationView study →Reference 21Zhang J et al. · 2023ReviewReview on the diverse biological effects of glabridinView study →}.

The honest posture is that almost none of this is human-tested as the isolate. The evidence is in-vitro and rodent, its systemic relevance is undercut by poor oral bioavailability, and it is important to separate glabridin from glycyrrhizin — glabridin is not the licorice component that raises blood pressure and lowers potassium. Its own cautions are different: estrogenic activity and cytochrome-P450 inhibition ^{16Reference 16Li G et al. · 2017Cytochrome P450 inhibition by three licorice species and fourteen licorice constituentsView study →}.

Skin Depigmentation — The Signature Activity

Glabridin’s defining, commercially load-bearing property is inhibition of tyrosinase, the rate-limiting enzyme of melanin synthesis. In the foundational study, glabridin inhibited tyrosinase activity in cultured B16 melanoma cells at 0.1–1.0 µg/mL without affecting DNA synthesis, and it suppressed UVB-induced pigmentation and erythema in guinea-pig skin — i.e. it lightened skin and calmed the inflammation that drives pigmentation, without being cytotoxic to the melanocytes ^{1Reference 1Yokota T et al. · 1998The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammationView study →}. Biophysical work has since mapped how it does this: glabridin binds tyrosinase directly, quenching its fluorescence and acting as a mixed-type inhibitor of the enzyme ^{2Reference 2Chen J et al. · 2016Inhibitory mechanisms of glabridin on tyrosinaseView study →}.

This is why glabridin — usually delivered as a purified fraction of licorice extract — is one of the standard “natural” alternatives to hydroquinone and kojic acid in skin-whitening and anti-melasma cosmetics. Newer mechanistic work extends the picture beyond the enzyme itself: a 2025 study identified glabridin among the active skin-whitening components of G. glabra extract and tied the effect to down-regulation of the CRTC1/MITF pathway — the transcriptional master-switch for melanogenesis — not just to direct tyrosinase blockade ^{3Reference 3Liu J et al. · 2025Glycyrrhiza glabra extract as a skin-whitening agent: identification of active components and CRTC1/MITF pathway-inhibition mechanismView study →}.

Two caveats keep this grounded. First, most of the depigmentation evidence is cell-culture and animal, plus the accumulated cosmetic-formulation record, rather than large controlled human trials of the isolate. Second, glabridin’s poor water solubility is a genuine delivery problem, which is why much recent work is on nano-encapsulation and solubility-enhanced forms to get it into skin at all ^{15Reference 15Hespeler D et al. · 2019Glabridin smartPearls — silica selection, production, amorphous stability and enhanced solubilityView study →}.

Anti-Inflammatory Activity in Skin

Glabridin’s second-best-developed story runs alongside the first and reinforces it: it is anti-inflammatory in inflammatory skin-disease models, acting largely through the TLR4 → MyD88 → NF-κB axis. In an atopic-dermatitis model it attenuated disease progression by down-regulating TLR4/MyD88/NF-κB signalling ^{7Reference 7Chang J et al. · 2021Glabridin attenuates atopic dermatitis progression through downregulating the TLR4/MyD88/NF-κB signaling pathwayView study →}, and in an imiquimod-induced psoriasis-like model it ameliorated the skin inflammation and lowered inflammatory cytokines ^{8Reference 8Li P et al. · 2018AnimalGlabridin, an isoflavan from licorice root, ameliorates imiquimod-induced psoriasis-like inflammation of BALB/c miceView study →}. Synthetic glabridin derivatives suppress LPS-induced inflammation via MAPK and NF-κB pathways, confirming the scaffold’s anti-inflammatory pharmacology ^{17Reference 17Kim HJ et al. · 2023Synthetic glabridin derivatives inhibit LPS-induced inflammation via MAPKs and NF-κB pathwaysView study →}. Because inflammation itself stimulates pigmentation, this anti-inflammatory action plausibly compounds the depigmenting effect in real skin.

What It's Used For

Beyond skin, glabridin has a genuinely broad activity list — but it is a preclinical list. The consistent theme is isolated molecule, in vitro or in rodents, with the systemic claims shadowed by low oral bioavailability.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Scores mix a mechanism-backed cosmetic use with a broad set of preclinical isolate findings, so read the per-row basis.

01Skin depigmentation (topical)Promising52%Defined tyrosinase-inhibition mechanism + CRTC1/MITF + cosmetic use ^{1,2,3Reference 1Yokota T et al. · 1998The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammationView study →Reference 2Chen J et al. · 2016Inhibitory mechanisms of glabridin on tyrosinaseView study →Reference 3Liu J et al. · 2025Glycyrrhiza glabra extract as a skin-whitening agent: identification of active components and CRTC1/MITF pathway-inhibition mechanismView study →}

02Anti-inflammatory (skin)Shaky38%Rodent isolate; TLR4/MyD88/NF-κB in atopic-dermatitis & psoriasis models ^{7,8,17Reference 7Chang J et al. · 2021Glabridin attenuates atopic dermatitis progression through downregulating the TLR4/MyD88/NF-κB signaling pathwayView study →Reference 8Li P et al. · 2018AnimalGlabridin, an isoflavan from licorice root, ameliorates imiquimod-induced psoriasis-like inflammation of BALB/c miceView study →Reference 17Kim HJ et al. · 2023Synthetic glabridin derivatives inhibit LPS-induced inflammation via MAPKs and NF-κB pathwaysView study →}

03Antioxidant / cardiovascularShaky33%Isolate protects LDL from oxidation; macrophage/atherosclerosis models ^{11,12Reference 11Kang MR et al. · 2015Cardiovascular protective effect of glabridin: implications in LDL oxidation and inflammationView study →Reference 12Carmeli E · 2008The effect of an endogenous antioxidant glabridin on oxidized LDLView study →}

04Metabolic / antidiabeticShaky30%Isolate AMPK/GLUT4 glucose uptake in myotubes; LFO-extract animal data ^{9,10Reference 9Sawada K et al. · 2014Glabridin induces glucose uptake via the AMP-activated protein kinase pathway in muscle cellsView study →Reference 10Yamashita Y et al. · 2019Liquorice flavonoid oil suppresses hyperglycaemia accompanied by skeletal muscle myocellular GLUT4 recruitmentView study →}

05Estrogenic / phytoestrogenShaky27%Binds human ER, stimulates estrogen-responsive readouts in vitro ^{5,6Reference 5Tamir S et al. · 2000Estrogenic and antiproliferative properties of glabridin from licorice in human breast cancer cellsView study →Reference 6Tamir S et al. · 2001Estrogen-like activity of glabrene and other constituents isolated from licorice rootView study →}

06Serotonergic / neuroShaky24%In-vitro SERT inhibition; recent rodent neuroinflammation model ^{4,20Reference 4Ofir R et al. · 2003Inhibition of serotonin re-uptake by licorice constituentsView study →Reference 20Shan M et al. · 2025AnimalGlabridin improves depression-like behaviors in mice by modulating neuroinflammationView study →}

Mechanisms

The load-bearing mechanism is tyrosinase inhibition — the only one tied to an established (cosmetic) use. The rest are real but preclinical, and the CYP row is a caution, not a benefit.

Pharmacokinetics

Glabridin’s pharmacokinetics are the reason to read its systemic claims cautiously. It is highly lipophilic and poorly water-soluble, which limits dissolution and absorption; in a Caco-2 intestinal model the absorbed species is the aglycone (not a conjugate), and oral dosing in rats confirms it reaches the circulation, establishing genuine but modest bioavailability ^{13Reference 13Ito C et al. · 2007AnimalAbsorption of dietary licorice isoflavan glabridin to blood circulation in ratsView study →}. The bigger constraint is first-pass metabolism: a detailed 2023 study characterised glabridin’s metabolic transformation and found the hepatic first-pass effect a major contributor to its low systemic exposure ^{14Reference 14Xie L et al. · 2023Comprehensive evaluation of metabolism and the contribution of the hepatic first-pass effect in the low bioavailability of glabridinView study →}. This is why so much formulation work — nano-encapsulation, amorphous “smartPearls,” lipid carriers — targets solubility and bioavailability rather than new pharmacology ^{15Reference 15Hespeler D et al. · 2019Glabridin smartPearls — silica selection, production, amorphous stability and enhanced solubilityView study →}. Distinctively, glabridin is also a cytochrome-P450 inhibitor (CYP3A4 and CYP2C isoforms among licorice constituents), which matters more for drug interactions than for its own clearance ^{16Reference 16Li G et al. · 2017Cytochrome P450 inhibition by three licorice species and fourteen licorice constituentsView study →}. A well-defined human half-life and oral-bioavailability figure for the isolate is not established.

Clinical Trials

There are no substantial controlled efficacy trials of isolated glabridin. Its real human footprint is cosmetic/topical (licorice-extract skin-lightening products), and the metabolic in-vivo evidence belongs to the licorice flavonoid oil extract, not the pure molecule ^{10Reference 10Yamashita Y et al. · 2019Liquorice flavonoid oil suppresses hyperglycaemia accompanied by skeletal muscle myocellular GLUT4 recruitmentView study →}. Everything else is in-vitro or rodent.

Last checked: July 2026.

Isolate vs. Plant Studies

Glabridin’s evidence base is overwhelmingly the isolated molecule — B16/melanocyte tyrosinase assays ^{1,2Reference 1Yokota T et al. · 1998The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammationView study →Reference 2Chen J et al. · 2016Inhibitory mechanisms of glabridin on tyrosinaseView study →}, the atopic-dermatitis and psoriasis mouse models ^{7,8Reference 7Chang J et al. · 2021Glabridin attenuates atopic dermatitis progression through downregulating the TLR4/MyD88/NF-κB signaling pathwayView study →Reference 8Li P et al. · 2018AnimalGlabridin, an isoflavan from licorice root, ameliorates imiquimod-induced psoriasis-like inflammation of BALB/c miceView study →}, LDL-oxidation and macrophage work ^{11,12Reference 11Kang MR et al. · 2015Cardiovascular protective effect of glabridin: implications in LDL oxidation and inflammationView study →Reference 12Carmeli E · 2008The effect of an endogenous antioxidant glabridin on oxidized LDLView study →}, the AMPK/GLUT4 myotube study ^{9Reference 9Sawada K et al. · 2014Glabridin induces glucose uptake via the AMP-activated protein kinase pathway in muscle cellsView study →}, the ER-binding assays ^{5Reference 5Tamir S et al. · 2000Estrogenic and antiproliferative properties of glabridin from licorice in human breast cancer cellsView study →} and the SERT work ^{4Reference 4Ofir R et al. · 2003Inhibition of serotonin re-uptake by licorice constituentsView study →} all test glabridin (or its derivatives) directly. As a mechanistic base for the isolate, that is a strength. The important exceptions are the whole-extract vehicles: the antidiabetic in-vivo data used licorice flavonoid oil (LFO/Glavonoid) — a glabridin-rich lipophilic extract, not the pure compound ^{10Reference 10Yamashita Y et al. · 2019Liquorice flavonoid oil suppresses hyperglycaemia accompanied by skeletal muscle myocellular GLUT4 recruitmentView study →} — and glabridin’s cosmetic use is almost always as a purified licorice-extract fraction. The transferability caveat runs the other way from most herbs here: there is plenty of isolate mechanism but almost no human isolate outcome data, and the systemic findings must be discounted for glabridin’s poor oral bioavailability. Whole-root licorice tea or tincture is a different exposure again — dominated by glycyrrhizin and the flavonoid glycosides liquiritin and isoliquiritin, not the lipophilic glabridin.

Prevalence in Nature

Glabridin is a chemotaxonomic marker of Glycyrrhiza glabra (European/Middle-Eastern licorice). It is concentrated in the root, at roughly 0.08–0.35% of dried root, as the principal isoflavan of the lipophilic licorice flavonoid oil ^{18Reference 18Wahab S et al. · 2021ReviewGlycyrrhiza glabra (licorice): a comprehensive review on its phytochemistry, biological activities, clinical evidence and toxicologyView study →}. Crucially it is largely absent from Chinese licorice (G. uralensis), whose defining lipophilic marker is instead glycyrrhizol A — so the presence of glabridin effectively distinguishes G. glabra material from G. uralensis ^{18Reference 18Wahab S et al. · 2021ReviewGlycyrrhiza glabra (licorice): a comprehensive review on its phytochemistry, biological activities, clinical evidence and toxicologyView study →}. This species discipline matters: much published “licorice” research uses G. uralensis or G. inflata, and glabridin-based findings should not be generalised across the genus.

Within G. glabra, glabridin sits in the same prenylated-isoflavonoid fraction as its relatives glabrene, glabrone and formononetin, next to the anti-inflammatory chalcone licochalcone A, the MAO-active glycyrrhisoflavone, and the root’s flavanone/chalcone glycosides liquiritin and isoliquiritin. Total root flavonoids run around 1–1.5% of dry weight, of which glabridin is a lipophilic minority component but the most pharmacologically studied ^{18,19Reference 18Wahab S et al. · 2021ReviewGlycyrrhiza glabra (licorice): a comprehensive review on its phytochemistry, biological activities, clinical evidence and toxicologyView study →Reference 19Asl MN · 2008ReviewReview of pharmacological effects of Glycyrrhiza sp. and its bioactive compoundsView study →}.

Discovery & Synthesis

Glabridin was first isolated from the root of Glycyrrhiza glabra as the major isoflavan of the root’s hydrophobic (“licorice flavonoid oil”) fraction, characterised by 20th-century Japanese natural-product chemists working on licorice isoflavonoids. Structurally it is a prenylated pterocarpan-adjacent isoflavan — a 2,3-dihydro isoflavone core bearing a fused dimethylpyran (prenyl-derived) ring and a resorcinol B-ring — and it occurs naturally as the single (R)-enantiomer.

Total synthesis of glabridin has been reported, and the scaffold is tractable enough that synthetic glabridin derivatives have been made and tested for anti-inflammatory activity ^{17Reference 17Kim HJ et al. · 2023Synthetic glabridin derivatives inhibit LPS-induced inflammation via MAPKs and NF-κB pathwaysView study →}. Manufacture today is predominantly extraction: commercial glabridin is purified from G. glabra root — typically as a standardised licorice-flavonoid concentrate (the Kaneka “Glavonoid”/licorice-flavonoid-oil line) for cosmetic and nutraceutical use — because the plant is a cheap, reliable source of the (R)-isomer. Its poor solubility drives ongoing carrier/encapsulation development rather than any change in source ^{15Reference 15Hespeler D et al. · 2019Glabridin smartPearls — silica selection, production, amorphous stability and enhanced solubilityView study →}.

Patents: not yet researched.

Toxicity & Safety

Glabridin carries a low flag. At the levels encountered in food (whole licorice) and in topical cosmetics it is well tolerated, and — importantly — it is not the licorice component responsible for the blood-pressure and potassium effects (that is glycyrrhizin and its aglycone glycyrrhetinic acid, chemically unrelated saponins). Its low oral bioavailability further limits systemic exposure from ingestion. Two real, mechanism-based cautions keep it from being negligible.

Safety at a Glance

✅ Low / no toxicityPhytoestrogenic

• Well tolerated at cosmetic/dietary exposure. Long topical use as a skin-lightening active and dietary presence in licorice, with low systemic exposure from poor oral bioavailability.
• Not the pseudoaldosteronism component. Glabridin is distinct from glycyrrhizin and does not drive licorice’s blood-pressure/potassium effects.
• Estrogenic (phytoestrogen). It binds the human estrogen receptor and is estrogenic at low concentrations (antiproliferative at high) — a reason for caution in hormone-sensitive conditions; reproductive/hormonal safety is decided on the herb or product page, not here ^{5,6Reference 5Tamir S et al. · 2000Estrogenic and antiproliferative properties of glabridin from licorice in human breast cancer cellsView study →Reference 6Tamir S et al. · 2001Estrogen-like activity of glabrene and other constituents isolated from licorice rootView study →}.
• CYP inhibition → drug-interaction potential. Glabridin (with other licorice constituents) inhibits CYP3A4 and CYP2C enzymes in vitro, so concentrated licorice-flavonoid extracts could in principle affect the metabolism of CYP-substrate drugs ^{16Reference 16Li G et al. · 2017Cytochrome P450 inhibition by three licorice species and fourteen licorice constituentsView study →}.
• Isolate human-safety data are limited. Dedicated high-dose human toxicology of pure glabridin is not established; most safety inference is from in-vitro/animal work and the whole-plant record.

Dosage

There is no established or recommended human oral dose for isolated glabridin. Its real-world use is topical and cosmetic, where licorice-extract skin-lightening products typically supply glabridin at roughly 0.1–0.5% of the formulation. Systemic figures in the literature are preclinical rodent research doses (e.g. the AMPK/glucose-uptake and LDL-oxidation studies) and the antidiabetic in-vivo work used the licorice flavonoid oil extract, not the pure molecule ^{9,10,12Reference 9Sawada K et al. · 2014Glabridin induces glucose uptake via the AMP-activated protein kinase pathway in muscle cellsView study →Reference 10Yamashita Y et al. · 2019Liquorice flavonoid oil suppresses hyperglycaemia accompanied by skeletal muscle myocellular GLUT4 recruitmentView study →Reference 12Carmeli E · 2008The effect of an endogenous antioxidant glabridin on oxidized LDLView study →}. Oral exposure is in any case constrained by glabridin’s poor water solubility and heavy first-pass metabolism ^{13,15Reference 13Ito C et al. · 2007AnimalAbsorption of dietary licorice isoflavan glabridin to blood circulation in ratsView study →Reference 15Hespeler D et al. · 2019Glabridin smartPearls — silica selection, production, amorphous stability and enhanced solubilityView study →}. These are research and formulation figures, not a personal recommendation.

References

1. Yokota T, Nishio H, Kubota Y, Mizoguchi M (1998). The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammation. Pigment Cell Research. https://pubmed.ncbi.nlm.nih.gov/9870547/
2. Chen J, et al. (2016). Inhibitory mechanisms of glabridin on tyrosinase. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. https://pubmed.ncbi.nlm.nih.gov/27288962/
3. Liu J, et al. (2025). Glycyrrhiza glabra extract as a skin-whitening agent: identification of active components and CRTC1/MITF pathway-inhibition mechanism. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/40350048/
4. Ofir R, Tamir S, Khatib S, Vaya J (2003). Inhibition of serotonin re-uptake by licorice constituents. Journal of Molecular Neuroscience. https://pubmed.ncbi.nlm.nih.gov/12794307/
5. Tamir S, et al. (2000). Estrogenic and antiproliferative properties of glabridin from licorice in human breast cancer cells. Cancer Research. https://pubmed.ncbi.nlm.nih.gov/11059763/
6. Tamir S, et al. (2001). Estrogen-like activity of glabrene and other constituents isolated from licorice root. Journal of Steroid Biochemistry and Molecular Biology. https://pubmed.ncbi.nlm.nih.gov/11595510/
7. Chang J, et al. (2021). Glabridin attenuates atopic dermatitis progression through downregulating the TLR4/MyD88/NF-κB signaling pathway. Genes & Genomics. https://pubmed.ncbi.nlm.nih.gov/34021857/
8. Li P, et al. (2018). Glabridin, an isoflavan from licorice root, ameliorates imiquimod-induced psoriasis-like inflammation of BALB/c mice. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/29665498/
9. Sawada K, Yamashita Y, Zhang T, et al. (2014). Glabridin induces glucose uptake via the AMP-activated protein kinase pathway in muscle cells. Molecular and Cellular Endocrinology. https://pubmed.ncbi.nlm.nih.gov/24953974/
10. Yamashita Y, et al. (2019). Liquorice flavonoid oil suppresses hyperglycaemia accompanied by skeletal muscle myocellular GLUT4 recruitment. International Journal of Food Sciences and Nutrition. https://pubmed.ncbi.nlm.nih.gov/30304967/
11. Kang MR, et al. (2015). Cardiovascular protective effect of glabridin: implications in LDL oxidation and inflammation. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/26526087/
12. Carmeli E, Fogelman Y (2008). The effect of an endogenous antioxidant glabridin on oxidized LDL. Journal of Basic and Clinical Physiology and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/19024795/
13. Ito C, et al. (2007). Absorption of dietary licorice isoflavan glabridin to blood circulation in rats. Journal of Nutritional Science and Vitaminology. https://pubmed.ncbi.nlm.nih.gov/17934243/
14. Xie L, et al. (2023). Comprehensive evaluation of metabolism and the contribution of the hepatic first-pass effect in the low bioavailability of glabridin. Journal of Agricultural and Food Chemistry. https://pubmed.ncbi.nlm.nih.gov/36649475/
15. Hespeler D, et al. (2019). Glabridin smartPearls — silica selection, production, amorphous stability and enhanced solubility. International Journal of Pharmaceutics. https://pubmed.ncbi.nlm.nih.gov/30836152/
16. Li G, et al. (2017). Cytochrome P450 inhibition by three licorice species and fourteen licorice constituents. European Journal of Pharmaceutical Sciences. https://pubmed.ncbi.nlm.nih.gov/28774812/
17. Kim HJ, et al. (2023). Synthetic glabridin derivatives inhibit LPS-induced inflammation via MAPKs and NF-κB pathways. Molecules. https://pubmed.ncbi.nlm.nih.gov/36903379/
18. Wahab S, et al. (2021). Glycyrrhiza glabra (licorice): a comprehensive review on its phytochemistry, biological activities, clinical evidence and toxicology. Plants (Basel). https://pubmed.ncbi.nlm.nih.gov/34961221/
19. Asl MN, Hosseinzadeh H (2008). Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytotherapy Research. https://pubmed.ncbi.nlm.nih.gov/18446848/
20. Shan M, et al. (2025). Glabridin improves depression-like behaviors in mice by modulating neuroinflammation. Neurochemical Research. https://pubmed.ncbi.nlm.nih.gov/41165967/
21. Zhang J, et al. (2023). Review on the diverse biological effects of glabridin. Drug Design, Development and Therapy. https://pubmed.ncbi.nlm.nih.gov/36647530/

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