Dataset Information

Glycyrrhizin through liquorice intake modulates ACE2 and HMGB1 levels-A pilot study in healthy individuals with implications for COVID-19 and ARDS.

ABSTRACT:

Background

Glycyrrhizin, an active component of liquorice root extract, exhibits antiviral and immunomodulatory properties by direct inhibition of the pro-inflammatory alarmin HMGB1 (High-mobility group box 1).

Objective

The aim of this study was to explore the role of liquorice intake on the viral entry receptor ACE2 (angiotensin-converting enzyme 2) and the immunoregulatory HMGB1 in healthy individuals and to explore HMGB1 expression in coronavirus disease 2019 (COVID-19) or non-COVID-19 in ARDS (acute respiratory distress syndrome patients).

Material and methods

This study enrolled 43 individuals, including hospitalised patients with i) acute respiratory distress syndrome (ARDS) due to COVID-19 (n = 7) or other underlying causes (n = 12), ii) mild COVID-19 (n = 4) and iii) healthy volunteers (n = 20). Healthy individuals took 50 g of liquorice (containing 3% liquorice root extract) daily for 7 days, while blood samples were collected at baseline and on day 3 and 7. Changes in ACE2 and HMGB1 levels were determined by Western blot analysis and enzyme-linked immunosorbent assay, respectively. Additionally, HMGB1 levels were measured in hospitalised COVID-19 patients with mild disease or COVID-19 associated acute respiratory distress syndrome (ARDS) and compared with a non-COVID-19-ARDS group.

Results

Liquorice intake significantly reduced after 7 days both cellular membranous ACE2 expression (-51% compared to baseline levels, p = 0.008) and plasma HMGB1 levels (-17% compared to baseline levels, p<0.001) in healthy individuals. Half of the individuals had a reduction in ACE2 levels of at least 30%. HMGB1 levels in patients with mild COVID-19 and ARDS patients with and without COVID-19 were significantly higher compared with those of healthy individuals (+317%, p = 0.002), but they were not different between COVID-19 and non-COVID-19 ARDS.

Conclusions

Liquorice intake modulates ACE2 and HMGB1 levels in healthy individuals. HMGB1 is enhanced in mild COVID-19 and in ARDS with and without COVID-19, warranting evaluation of HMGB1 as a potential treatment target and glycyrrhizin, which is an active component of liquorice root extract, as a potential treatment in COVID-19 and non-COVID-19 respiratory disease.

SUBMITTER: Buder F

PROVIDER: S-EPMC9576069 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Glycyrrhizin through liquorice intake modulates ACE2 and HMGB1 levels-A pilot study in healthy individuals with implications for COVID-19 and ARDS.

Buder Felix F Selejan Simina-Ramona SR Hohl Mathias M Kindermann Michael M Herr Christian C Lepper Philipp M PM Bals Robert R Salzberger Bernd B Mahfoud Felix F Böhm Michael M

PloS one 20221017 10

<h4>Background</h4>Glycyrrhizin, an active component of liquorice root extract, exhibits antiviral and immunomodulatory properties by direct inhibition of the pro-inflammatory alarmin HMGB1 (High-mobility group box 1).<h4>Objective</h4>The aim of this study was to explore the role of liquorice intake on the viral entry receptor ACE2 (angiotensin-converting enzyme 2) and the immunoregulatory HMGB1 in healthy individuals and to explore HMGB1 expression in coronavirus disease 2019 (COVID-19) or non ...[more]

PMID: 36251689

Similar Datasets

Project description:BackgroundTo unravel true links between diet and health, it is important that dietary exposure is accurately measured. Currently, mainly self-reporting methods (e.g. food frequency questionnaires and 24-h recalls) are used to assess food intake in epidemiological studies. However, these traditional instruments are subjective measures and contain well-known biases. Especially, estimating the intake of the group of confectionary products, such as products containing cocoa and liquorice, remains a challenge. The use biomarkers of food intake (BFIs) may provide a more objective measurement. However, an overview of current candidate biomarkers and their validity is missing for both cocoa- and liquorice-containing foods.ObjectiveThe purpose of the current study was to (1) identify currently described candidate BFIs for cocoa (products) and liquorice, (2) to evaluate the validity of these identified candidate BFIs and (3) to address further validation and/or identification work to be done.MethodsThis systematic review was based on a comprehensive literature search of three databases (PubMed, Scopus and ISI web of Science), to identify candidate BFIs. Via a second search step in the Human Metabolome Database (HMDB), the Food Database (FooDB) and Phenol-Explorer, the specificity of the candidate BFIs was evaluated, followed by an evaluation of the validity of the specific candidate BFIs, via pre-defined criteria.ResultsIn total, 37 papers were included for cocoa and 8 papers for liquorice. For cocoa, 164 unique candidate BFIs were obtained, and for liquorice, four were identified in total. Despite the high number of identified BFIs for cocoa, none of the metabolites was specific. Therefore, the validity of these compounds was not further examined. For liquorice intake, 18-glycyrrhetinic acid (18-GA) was found to have the highest assumed validity.ConclusionsFor cocoa, specific BFIs were missing, mainly because the individual BFIs were also found in foods having a similar composition, such as tea (polyphenols) or coffee (caffeine). However, a combination of individual BFIs might lead to discriminating profiles between cocoa (products) and foods with a similar composition. Therefore, studies directly comparing the consumption of cocoa to these similar products are needed, enabling efforts to find a unique profile per product. For liquorice, we identified 18-GA as a promising BFI; however, important information on its validity is missing; thus, more research is necessary. Our findings indicate a need for more studies to determine acceptable BFIs for both cocoa and liquorice.

Project description:Liquorice is usually used as crude drug in traditional Japanese Kampo medicine and traditional Chinese medicine. Liquorice-containing glycyrrhizin (GL) can cause pseudohyperaldosteronism as a side effect. Previously, we identified 18β-glycyrrhetyl-3-O-sulfate (3) as a GL metabolite in Eisai hyperbilirubinuria rats (EHBRs) with the dysfunction of multidrug resistance-related protein (Mrp2). We speculated that 3 was associated with the onset of liquorice-induced pseudohyperaldosteronism, because it was mainly detected in serum of patients with suspected to have this condition. However, it is predicted that other metabolites might exist in the urine of EHBRs orally treated with glycyrrhetinic acid (GA). We explored other metabolites in the urine of EHBRs, and investigated the pharmacokinetic profiles of the new metabolite in EHBRs and normal Sprague-Dawley rats. We further analyzed the serum concentrations of the new metabolite in the patients of pseudohyperaldosteronism. Finally, we developed the analyzing method of these metabolites as a preventive biomarker for the onset of pseudohyperaldosteronism using an enzyme-linked immunosorbent assay (ELISA). We isolated a new GL metabolite, 18β-glycyrrhetyl-3-O-sulfate-30-O-glucuronide (4). Compound 4 significantly inhibited rat type-2 11β-hydroxysteroid dehydrogenase (11β-HSD2) and was a substrate of both organic anion transporter (OAT) 1 and OAT3. Compound 4 was also detected in the serum of patients with suspected pseudohyperaldosteronism at an approximately 10-fold lower concentrations than 3, and these concentrations were positively correlated. Compound 4 showed a lower serum concentration and weaker inhibitory titer on 11β-HSD2 than 3. We developed an enzyme-linked immunosorbent assay system using an anti-18β-glycyrrhetyl-3-O-glucuronide (3MGA) monoclonal antibody to measure the serum concentration of 3 to facilitate the measurement of biomarkers to predict the onset of pseudohyperaldosteronism. Although we found 4 as the secondary candidate causative agent, 3 could be the main potent preventive biomarker of liquorice-induced pseudohyperaldosteronism. Compound 3 was detected in serum at a higher concentration than GA and 4, implying that 3 may be a pharmacologically active ingredient mediating not only the development of pseudohyperaldosteronism but anti-inflammatory effects in humans administered GL or other liquorice-containing preparations.

Dataset Information

Glycyrrhizin through liquorice intake modulates ACE2 and HMGB1 levels-A pilot study in healthy individuals with implications for COVID-19 and ARDS.

Background

Objective

Material and methods

Results

Conclusions

Publications

Glycyrrhizin through liquorice intake modulates ACE2 and HMGB1 levels-A pilot study in healthy individuals with implications for COVID-19 and ARDS.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets