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

• Published in: PloS one 2022-10, Vol.17 (10), p.e0275181-e0275181
• Main Authors: Buder, Felix, Selejan, Simina-Ramona, Hohl, Mathias, Kindermann, Michael, Herr, Christian, Lepper, Philipp M, Bals, Robert, Salzberger, Bernd, Mahfoud, Felix, Böhm, Michael
• Format: Article
• Language: English
• Subjects: ACE2; Acute respiratory distress syndrome; Angiotensin; Angiotensin converting enzyme; Angiotensin-converting enzyme 2; Antiviral activity; Biology and life sciences; Blood pressure; Care and treatment; Consent; Coronaviruses; COVID-19; Diagnosis; Enzyme-linked immunosorbent assay; Glycyrrhizin; Health aspects; Health services; HMGB1 protein; Immunomodulation; Immunoregulation; Inflammation; Laboratories; Liquorice; Medicine and Health Sciences; Obesity; Patients; Peptidyl-dipeptidase A; Proteins; Respiratory diseases; Respiratory distress syndrome; Severe acute respiratory syndrome coronavirus 2; Therapeutic applications; Viral diseases
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0275181

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