Ursolic acid and SARS-CoV-2 infection: a new horizon and perspective

Abstract

SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) has been identified as the source of a world coronavirus pandemic in 2019. Covid-19 is considered a main respiratory disease-causing viral pneumonia and, in severe cases, leads to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Although, extrapulmonary manifestations of Covid-19 like neurological, cardiovascular, and gastrointestinal have been confirmed. Exaggerated immune response and release of a high amount of pro-inflammatory cytokines may progress, causing a cytokine storm. Consequently, direct and indirect effects of SARS-CoV-2 infection can evolve into systemic complications due to the progression of hyper inflammation, oxidative stress and dysregulation of the renin-angiotensin system (RAS). Therefore, anti-inflammatory and antioxidant agents could be efficient in alleviating these disorders. Ursolic acid has anti-inflammatory, antioxidant, and antiviral effects; it reduces the release of pro-inflammatory cytokines, improves anti-inflammatory cytokines, and inhibits the production of reactive oxygen species (ROS). In virtue of its anti-inflammatory and antioxidant effects, ursolic acid may minimize SARS-CoV-2 infection-induced complications. Also, by regulating RAS and inflammatory signaling pathways, ursolic acid might effectively reduce the development of ALI in ARDS in Covid-19. In this state, this perspective discusses how ursolic acid can mitigate hyper inflammation and oxidative stress in Covid-19.

Keywords: Acute lung injury; Antiviral; Covid-19; Immunity; Oxidative stress; Pandemics.

Fig. 1

Ursolic acid Chemical Structure

Fig. 2

The probable role of ursolic acid in Covid-19: Ursolic acid inhibits release of pro-inflammatory cytokines as well as SARS-CoV-2 proliferation. Ursolic acid augments antioxidants and release of anti-inflammatory cytokines, which reduce oxidative stress and inflammatory disorders leading suppression development of ALI and ARDS

Fig. 3

The potential effects of ursolic acid on RAS in Covid-19. Angiotensin I (AngI) is converted by ACE to AngII which activates AT1R leading to the induction of oxidative stress and inflammation. Covid-19 down-regulates ACE2 causing the elevation in AngII with reduction of Ang1-7 and Ang1-9. Ursolic acid inhibits ACE with increasing expression of ACE2. These changes by ursolic acid decrease the risk of development of ALI and ARDS

Fig. 4

The potential effects of ursolic acid on inflammatory signaling pathways in Covid-19. SARS-CoV-2 infection activates nod-like receptor pyrin 3 (NLRP3) inflammasome, mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 3(STAT3), phosphatidylinositol 3 kinase/Akt (PI3K/Akt), nuclear factor kappa B (NF-κB), advanced glycation end-products (AGEs) and its receptors (RAGE), high mobility group box protein 1(HMGB1) and mechanistic target of rapamycin (mTOR) pathway with inhibition of autophagy. ursolic acid inhibits these inflammatory signaling pathways and activates autophagy