Food Enrichment with Glycyrrhiza glabra Extract Suppresses ACE2 mRNA and Protein Expression in Rats—Possible Implications for COVID-19

Abstract

Angiotensin converting enzyme 2 (ACE2) is a key entry point of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus known to induce Coronavirus disease 2019 (COVID-19). We have recently outlined a concept to reduce ACE2 expression by the administration of glycyrrhizin, a component of Glycyrrhiza glabra extract, via its inhibitory activity on 11beta hydroxysteroid dehydrogenase type 2 (11betaHSD2) and resulting activation of mineralocorticoid receptor (MR). We hypothesized that in organs such as the ileum, which co-express 11betaHSD2, MR and ACE2, the expression of ACE2 would be suppressed. We studied organ tissues from an experiment originally designed to address the effects of Glycyrrhiza glabra extract on stress response. Male Sprague Dawley rats were left undisturbed or exposed to chronic mild stress for five weeks. For the last two weeks, animals continued with a placebo diet or received a diet containing extract of Glycyrrhiza glabra root at a dose of 150 mg/kg of body weight/day. Quantitative PCR measurements showed a significant decrease in gene expression of ACE2 in the small intestine of rats fed with diet containing Glycyrrhiza glabra extract. This effect was independent of the stress condition and failed to be observed in non-target tissues, namely the heart and the brain cortex. In the small intestine we also confirmed the reduction of ACE2 at the protein level. Present findings provide evidence to support the hypothesis that Glycyrrhiza glabra extract may reduce an entry point of SARS-CoV-2. Whether this phenomenon, when confirmed in additional studies, is linked to the susceptibility of cells to the virus requires further studies.

Glycyrrhizic Acid Inhibits SARS-CoV-2 Infection by Blocking Spike Protein-Mediated Cell Attachment

“…Cinatl and colleagues found that glycyrrhizin was among the most active compounds tested in inhibiting replication of the SARS-CoV [ 12 ]. Thus, licorice and GA could be an old weapon against emerging diseases [ 13 , 14 ].…”

The Role of Herbal and Nutritional Treatments in the Fight against COVID-19 and Other Respiratory Tract Infections

“…In rat models, diets supplemented with 150 mg/kg/day Glycyrrhizin compared to placebo showed a reduction in the expression of ACE2 protein and gene, therefore reducing the uptake of COVID-19 at the cellular level and its spread. A significant main effect was detected in the MRNA ACE2 coding at the level of the small intestine (p = 0.04) [12].…”

“…The top two herbs used were Radix astragali and Glycyrrhizae Radix Et Rhizoma [13]. Both are associated with having qi blood, a tonifying effect that replenishes the body when weak [12]. Individual case studies also tested the effectiveness of Shuanghuanglian oral liquid (SHL) (including honeysuckle, forsythia, and Scutellaria baicalensis).…”

Revisiting liquorice (Glycyrrhiza glabra L.) as anti-inflammatory, antivirals and immunomodulators: Potential pharmacological applications with mechanistic insight.

“…G. glabra and its active components have been shown promising results to combat SARS-CoV-2 infection and can be useful in treating patients with COVID-19 as on scientific evidences collected from some of the recently published reviews ( Bailly and Vergoten, 2020 ; Fatima et al, 2020 ; Huaccho-Rojas et al, 2020 ; Jezova et al, 2020 ; Murck, 2020 ; Srivastava et al, 2020 ; Adithya et al, 2021 ; Boozari and Hosseinzadeh, 2021 ; Jalali et al, 2021 ; Khan et al, 2021 ; Idrees et al, 2021 ; Brendler et al, 2021 ; Diomede et al, 2021 ; Liana and Phanumartwiwath, 2021 ; Malekmohammad et al, 2021 ; Merarchi et al, 2021 ). Several mechanisms have been identified and have been depicted in figure 4 .…”