Potential Role of Nrf2 Activators with Dual Antiviral and Anti-Inflammatory Properties in the Management of Viral Pneumonia

Figures & data

Table 1 Summary of the Effects of Nrf2 Activators and Macrolides on the Pathophysiology of Viral Pneumonia/ARDS Based on Current Evidence

	Curcumin		Sulforaphane		Macrolides
Positive effect on the pathophysiology of viral pneumonia/ARDS	Influenza virus	Other disease models	Influenza virus	Other disease models	Influenza virus	Other disease models
Antiviral effect	In vitro^Citation5,Citation10,Citation11 and in vivo^Citation11	In vitro and in vivo studies showed board spectrum antiviral effect.^Citation6,Citation7	In vitro: antiviral effect against influenza virus^Citation23 In vivo: antiviral effect against RSV^Citation22		In vitro and in vivo: antiviral effect against rhinovirus, RSV, and influenza virus^Citation35
Decreased infiltration of inflammatory cells	In vivo^Citation9,Citation10	In vivo: mouse model of reovirus infection^Citation8	–	In vivo: oleic acid induced ARDS rabbit model^Citation42	In vivo^Citation43	Various inflammatory disease models^Citation36
Decreased production of proinflammatory cytokines	In vitro and in vivo^Citation9^–^Citation11	In vivo: mouse model of reovirus infection^Citation8	–	In vivo: LPS-induced acute lung injury mouse model^Citation44	In vitro, in vivo, and human studies^Citation35
Increased production of granzyme b by NK cells	–	–	Human study^Citation24	–	–	–
Decreased levels of MMPs	In vitro and in vivo^Citation10	In vivo: LPS and ovalbumin challenged mouse model^Citation45	–	In vivo: LPS-induced acute lung injury mouse model^Citation44	In vivo^Citation43	Various inflammatory disease models^Citation36
Inhibition of fibrosis	–	In vivo: mouse model of reovirus infection^Citation8	–	–	–	–
Inhibition of mucin secretion	–	In vitro: LPS stimulated human bronchial epithelial cells (NCI-H292)^Citation13 In vivo: LPS intratracheal instillation mouse model^Citation13	–	In vitro: neutrophil elastase challenged human airway epithelial cells (NCI-H292)^Citation46	–	In vitro: rhinovirus infected human tracheal epithelial cells^Citation47
Positive effects against bacterial infection and modulation of scavenger receptor expression	–	In vitro and in vivo studies showed board spectrum antibacterial effect.^Citation6,Citation7 In vitro: enhanced phagocytosis of inactivated Staphylococcus aureus bioparticles through up-regulation of CD36 surface expression on macrophages^Citation48	In vitro: improved bacterial phagocytosis in INFγ treated macrophages through MARCO upregulation^Citation27 In vivo: improved bacterial clearance in a postinfluenza bacterial pneumonia mouse model^Citation27	In vitro: improved phagocytosis of bacteria by alveolar macrophages from patients with COPD^Citation28,Citation49 In vivo: increased MARCO expression and enhanced phagocytic ability of macrophages in a mouse model^Citation49 Human study: increased MARCO expression in peripheral blood mononuclear cells^Citation49	Antibacterial effect by inhibiting bacterial ribosome 50S subunit. In vivo: mitigated influenza-induced decline in MARCO expression in a mouse model of COPD with postinfluenza bacterial pneumonia^Citation50	–
Increased survival	In vivo^Citation10,Citation11	In vivo: CLP murine model of sepsis^Citation31,Citation33	In vivo: postinfluenza bacterial pneumonia mouse model^Citation27	In vivo: HMGB1-induced mouse sepsis model^Citation32	In vivo^Citation35	Human study: decreased mortality in patients with ARDS^Citation51

Abbreviations: MMP, matrix metalloproteinase; CLP, cecal ligation and puncture; COPD, chronic obstructive pulmonary disease.

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