The protective effect of xanthenone against LPS-induced COVID-19 acute respiratory distress syndrome (ARDS) by modulating the ACE2/Ang-1-7 signaling pathway

Abstract

OBJECTIVE: Acute respiratory distress syndrome (ARDS) is an inflammatory lung disease that has a high rate of morbidity and mortality. It’s an acute diffusive lung injury caused by the release of pro-inflammatory cytokines into the lungs. Specific microRNAs have been identified to play a crucial role in the renin-angiotensin system signaling pathways the main pathophysiological pathway responsible for ARDS. Since the ARDS life-threatening complication associated with COVID-19 is an ongoing challenge, this current study aimed to investigate the potential efficacy of xanthenone in the treatment of ARDS induced with LPS in mice through ACE2 activation and modulation of miR-200 and ACE2/Ang 1-7 pathways.

MATERIALS AND METHODS: Mice were categorized into three groups randomly. The first set of mice served as the normal control group. The ARDS group was injected with LPS (15 mg/kg; i.p.). The last group was treated with xanthenone (2 mg/kg/day; p.o.) for one week before the LPS injection.

RESULTS: Xanthenone treatment resulted in a significant down-regulation of miRNA-200 expression, leading to the activation of ACE2 accompanied with marked inhibition of Angiotensin II as well as increases the levels of Ang 1-7 and SP-A.

CONCLUSIONS: Xanthenone has the potential to be a promising therapeutic drug for the treatment of ARDS COVID-19 complication through activation of ACE2/Ang 1-7 pathways.