Glycyrrhetinic Acid and Acute Irritant Dermatitis
Effects of Glycyrrhetinic Acid on Human Skin in an Acute Irritant Contact Dermatitis Model
Irritant dermatitis is one of the most common inflammatory skin disorders, caused by exposure to external substances that induce inflammation and immune activation. Standard management includes avoidance of irritants, restoration of the skin barrier using emollients, and the application of anti-inflammatory drugs such as topical corticosteroids. However, due to the risks associated with long-term corticosteroid use, there is an interest in developing emollient formulations enriched with bioactive compounds possessing anti-inflammatory properties. Among those promising compounds is glycyrrhetinic acid.
18β-Glycyrrhetinic acid, a bioactive component of licorice root extract, exhibits potent anti-inflammatory and antioxidant effects. Topical application has demonstrated beneficial outcomes in conditions such as atopic dermatitis, acne, pruritus, and UVB-induced skin damage. Its proposed mechanisms of action include inhibition of key inflammatory enzymes (COX, 5-LOX, iNOS) and promotion of skin regeneration through stimulation of aquaporin-3 expression and enhancement of epidermal turnover.
Topical application of formulations containing 18β-glycyrrhetinic acid will improve skin parameter disturbances caused by irritation induced with sodium lauryl sulfate.
This study aims to evaluate the effects of 18β-glycyrrhetinic acid on human skin parameters in an acute irritant dermatitis model induced by sodium lauryl sulfate, providing further insight into its potential role as an anti-inflammatory and barrier-restoring agent.
Funding:
Funded by the European Union - NextGenerationEU. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Commission. Neither the European Union nor the European Commission can be held responsible for them.
Study Overview
Status
Conditions
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Split, Croatia, 21000
- Recruiting
- University of Split School of Medicine
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Principal Investigator:
- Dario Leskur, asst. prof., MPharm, PhD
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Contact:
- Dario Leskur
- Phone Number: +38521557868
- Email: dleskur@mefst.hr
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Healthy adult participants aged 18 years or older, of any sex.
- Intact, healthy skin at the test sites.
- No use of systemic or topical corticosteroids, immunomodulators, or antihistamines within the previous three months.
- No use of topical emollients on the test sites within the previous seven days.
Exclusion Criteria:
- Pregnant women, women suspected of being pregnant, and breastfeeding women.
- Non-compliance with the study protocol.
- Voluntary withdrawal or personal decision not to continue participation.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Other: No Treatment and Intact skin
No topical product will be applied.
Intact skin.
|
Designated test area with no topical application after irritation (on the irritated forearm) and on corresponding intact skin (on the non-irritated forearm).
Serves as a baseline reference for spontaneous recovery and physiological skin variability.
|
|
Placebo Comparator: Placebo and Intact skin
Topical placebo formulation identical in appearance and vehicle composition to the active preparation but without glycyrrhetinic acid.
Used to control for vehicle effects on skin parameters.
Intact skin.
|
Topical formulation identical in composition to the active preparations but without glycyrrhetinic acid. Used to evaluate the effect of the formulation vehicle on skin parameters. Applied daily to designated test sites on both irritated and intact forearm areas for the duration of the study. |
|
Other: No Treatment and Irritation
No topical product will be applied.
SLS induced skin irritation.
|
Designated test area with no topical application after irritation (on the irritated forearm) and on corresponding intact skin (on the non-irritated forearm).
Serves as a baseline reference for spontaneous recovery and physiological skin variability.
Skin irritation will be induced on 4 defined test sites on one forearm (randomly selected forearm) using 60 uL of 1% w/v sodium lauryl sulfate (SLS) aqueous solution under occlusion for a defined period to create a controlled model of acute irritant dermatitis. The contralateral forearm will remain untreated and serve as intact skin for comparison. Following the induction phase, all test products (placebo and active formulations) will be applied to both irritated and intact sites according to the treatment allocation. |
|
Placebo Comparator: Placebo and Irritation
Topical placebo formulation identical in appearance and vehicle composition to the active preparation but without glycyrrhetinic acid.
Used to control for vehicle effects on skin parameters.
SLS induced skin irritation.
|
Topical formulation identical in composition to the active preparations but without glycyrrhetinic acid. Used to evaluate the effect of the formulation vehicle on skin parameters. Applied daily to designated test sites on both irritated and intact forearm areas for the duration of the study. Skin irritation will be induced on 4 defined test sites on one forearm (randomly selected forearm) using 60 uL of 1% w/v sodium lauryl sulfate (SLS) aqueous solution under occlusion for a defined period to create a controlled model of acute irritant dermatitis. The contralateral forearm will remain untreated and serve as intact skin for comparison. Following the induction phase, all test products (placebo and active formulations) will be applied to both irritated and intact sites according to the treatment allocation. |
|
Experimental: Glycyrrhetinic Acid (low-dose formulation) and Intact skin
Topical formulation containing a low concentration of 18β-glycyrrhetinic acid.
Designed to evaluate the effects of different doses of the active compound on intact skin parameters.
Applied to intact skin.
|
Topical formulation containing a low concentration of 18β-glycyrrhetinic acid.
Designed to assess the effects of the active compound at a low dose on skin barrier recovery and skin parameters following SLS-induced irritation.
The formulation is applied daily to designated test sites on both irritated and intact forearm areas for the duration of the study.
|
|
Experimental: Glycyrrhetinic Acid (high-dose formulation) and Intact skin
Topical formulation containing a high concentration of 18β-glycyrrhetinic acid.
Designed to evaluate the dose-dependent effects of the active compound on intact skin parameters.
Applied to intact skin.
|
Topical formulation containing a high concentration of 18β-glycyrrhetinic acid.
Designed to assess the effects of the active compound at a high dose on skin barrier recovery and skin parameters following SLS-induced irritation.
The formulation is applied daily to designated test sites on both irritated and intact forearm areas for the duration of the study.
|
|
Experimental: Glycyrrhetinic Acid (low-dose formulation) and Irritation
Topical formulation containing a low concentration of 18β-glycyrrhetinic acid.
Used to assess the effects of a low dose on anti-inflammatory and skin barrier-restoring outcomes following SLS-induced skin irritation, and to evaluate potential dose-dependent effects compared with the intermediate- and high-dose formulations and placebo.
Applied to SLS-irritated skin.
|
Skin irritation will be induced on 4 defined test sites on one forearm (randomly selected forearm) using 60 uL of 1% w/v sodium lauryl sulfate (SLS) aqueous solution under occlusion for a defined period to create a controlled model of acute irritant dermatitis. The contralateral forearm will remain untreated and serve as intact skin for comparison. Following the induction phase, all test products (placebo and active formulations) will be applied to both irritated and intact sites according to the treatment allocation.
Topical formulation containing a low concentration of 18β-glycyrrhetinic acid.
Designed to assess the effects of the active compound at a low dose on skin barrier recovery and skin parameters following SLS-induced irritation.
The formulation is applied daily to designated test sites on both irritated and intact forearm areas for the duration of the study.
|
|
Experimental: Glycyrrhetinic Acid (high-dose formulation) and Irritation
Topical formulation containing a high concentration of 18β-glycyrrhetinic acid.
Used to assess the effects of a high dose on anti-inflammatory and skin barrier-restoring outcomes following SLS-induced skin irritation, and to evaluate potential dose-dependent effects compared with the low- and intermediate-dose formulations and placebo.
Applied to SLS-irritated skin.
|
Skin irritation will be induced on 4 defined test sites on one forearm (randomly selected forearm) using 60 uL of 1% w/v sodium lauryl sulfate (SLS) aqueous solution under occlusion for a defined period to create a controlled model of acute irritant dermatitis. The contralateral forearm will remain untreated and serve as intact skin for comparison. Following the induction phase, all test products (placebo and active formulations) will be applied to both irritated and intact sites according to the treatment allocation.
Topical formulation containing a high concentration of 18β-glycyrrhetinic acid.
Designed to assess the effects of the active compound at a high dose on skin barrier recovery and skin parameters following SLS-induced irritation.
The formulation is applied daily to designated test sites on both irritated and intact forearm areas for the duration of the study.
|
|
Experimental: Glycyrrhetinic Acid (intermediate-dose formulation) and Intact skin
Topical formulation containing an intermediate concentration of 18β-glycyrrhetinic acid.
Designed to evaluate the effects of different doses of the active compound on intact skin parameters.
Applied to intact skin.
|
Topical formulation containing an intermediate concentration of 18β-glycyrrhetinic acid.
Designed to assess the effects of the active compound at an intermediate dose on skin barrier recovery and skin parameters following SLS-induced irritation.
The formulation is applied daily to designated test sites on both irritated and intact forearm areas for the duration of the study.
|
|
Experimental: Glycyrrhetinic Acid (intermediate-dose formulation) and Irritation
Topical formulation containing an intermediate concentration of 18β-glycyrrhetinic acid.
Used to assess the effects of an intermediate dose on anti-inflammatory and skin barrier-restoring outcomes following SLS-induced skin irritation, and to evaluate potential dose-dependent effects compared with the low- and high-dose formulations and placebo.
Applied to SLS-irritated skin.
|
Skin irritation will be induced on 4 defined test sites on one forearm (randomly selected forearm) using 60 uL of 1% w/v sodium lauryl sulfate (SLS) aqueous solution under occlusion for a defined period to create a controlled model of acute irritant dermatitis. The contralateral forearm will remain untreated and serve as intact skin for comparison. Following the induction phase, all test products (placebo and active formulations) will be applied to both irritated and intact sites according to the treatment allocation.
Topical formulation containing an intermediate concentration of 18β-glycyrrhetinic acid.
Designed to assess the effects of the active compound at an intermediate dose on skin barrier recovery and skin parameters following SLS-induced irritation.
The formulation is applied daily to designated test sites on both irritated and intact forearm areas for the duration of the study.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Transepidermal water loss
Time Frame: 1st, 2nd, 3rd, 4th, 5th, 8th and 10th day of the trial
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Tewameter will be used to assess skin barrier function as a measurement of the water loss (g/m2/h).
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1st, 2nd, 3rd, 4th, 5th, 8th and 10th day of the trial
|
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Hydration
Time Frame: 1st, 2nd, 3rd, 4th, 5th, 8th and 10th day of the trial
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Corneometer will be used to estimate skin dryness.
It is a relative measurement and uses arbitrary units (AU).
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1st, 2nd, 3rd, 4th, 5th, 8th and 10th day of the trial
|
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Erythema
Time Frame: 1st, 2nd, 3rd, 4th, 5th, 8th and 10th day of the trial
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Mexameter will be used to assess erythema.
It is a relative measurement and uses arbitrary units (AU).
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1st, 2nd, 3rd, 4th, 5th, 8th and 10th day of the trial
|
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Skin elasticity
Time Frame: 1st, 2nd, 3rd, 4th, 5th, 8th and 10th day of the trial
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Cutometer will be used to assess skin elasticity.
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1st, 2nd, 3rd, 4th, 5th, 8th and 10th day of the trial
|
Collaborators and Investigators
Collaborators
Publications and helpful links
General Publications
- Scheinman PL, Vocanson M, Thyssen JP, Johansen JD, Nixon RL, Dear K, Botto NC, Morot J, Goldminz AM. Contact dermatitis. Nat Rev Dis Primers. 2021 May 27;7(1):38. doi: 10.1038/s41572-021-00271-4.
- Johansen JD, Bonefeld CM, Schwensen JFB, Thyssen JP, Uter W. Novel insights into contact dermatitis. J Allergy Clin Immunol. 2022 Apr;149(4):1162-1171. doi: 10.1016/j.jaci.2022.02.002. Epub 2022 Feb 18.
- Kang SY, Um JY, Chung BY, Lee SY, Park JS, Kim JC, Park CW, Kim HO. Moisturizer in Patients with Inflammatory Skin Diseases. Medicina (Kaunas). 2022 Jul 1;58(7):888. doi: 10.3390/medicina58070888.
- Weisshaar E. Chronic Hand Eczema. Am J Clin Dermatol. 2024 Nov;25(6):909-926. doi: 10.1007/s40257-024-00890-z. Epub 2024 Sep 19.
- Kowalska A, Kalinowska-Lis U. 18beta-Glycyrrhetinic acid: its core biological properties and dermatological applications. Int J Cosmet Sci. 2019 Aug;41(4):325-331. doi: 10.1111/ics.12548. Epub 2019 Jun 28.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2181-198-03-04-25-0072
- IP-UNIST-35 (Other Grant/Funding Number: Funded by the European Union - NextGenerationEU)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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