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.
Highlights
Introduction iationsThe coronavirus pandemic 2019 (COVID-19) has clearly revealed the need to search for new therapeutic options including natural products as food supplements [1,2]
The angiotensin converting enzyme 2 (ACE2) serves as an entry point for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which leads to COVID-19
Two-way ANOVA revealed a signifiexpression of ACE2 was significantly lower in rats fed the diet with Glycyrrhiza glabra cant main effect of treatment (F(1,44) = 4.41; p = 0.0415) on concentrations of mRNA coding extract compared to rats fed the placebo diet (Figure 1A)
Summary
The coronavirus pandemic 2019 (COVID-19) has clearly revealed the need to search for new therapeutic options including natural products as food supplements [1,2]. The angiotensin converting enzyme 2 (ACE2) serves as an entry point for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which leads to COVID-19. Reducing ACE2 expression would reduce the number of access points of the virus to the body during primary infection, and potentially the spread inside the body. Cells which are susceptible to infection with SARS-CoV-2 appear to be primarily type II pneumocytes, intestinal absorptive enterocytes, and nasal goblet secretory cells [3]. The identification of mechanisms to reduce membrane ACE2 expression at these cells may be valuable. We have recently proposed that glycyrrhizin, a key component of an extract from
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