Table 3.

Protective  effect  of glycyrrhizin and licorice extract against  acute lung injury that  may occur due to COVID-19 or others in articles published from 2011 to 2020.

Active substance used	Method of research	Major finding	Mechanism of actions	References
Glycyrrhizin Isoliquiritigenin (ISL), a flavonoid isolated from licorice. Isoliquiritigenin ILG Glycyrrhizin intraperitoneally administered Glycyrrhizin Glycyrrhizin Glycyrrhizic acid (GA) Ethanolic extract of Licorice( G. glabra ) Glycyrrhizic acid (GL), aqueous extract . Glycyrrhetinic acid (GA) is a major bioactive hydrolysis product of GL. Glycyrrhizin(GL) Glycyrrhizic acid (GA), and tilianin (TN). Approved SKBHT, berbal combination contain licorice.	Lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. LPS in RAW 264.7 cells. & mice. Animal model of LPS-induced ALI. LPS-induced ALI in a mouse model. Mice + LPS LPS induce ALI in a mouse model. LPS-induced ALI in mice. ALI murine models were established by intratracheal instillation of bacterial LPS. Murine hepatitis virus (MHV) infection model. Human alveolar epithelial cell line A549 and normal human bronchial epithelial cell line BEAS-2B Mouse model of Chronic obstructive pulmonary disease COPD. Mouse model of ALI	GL potently protected against LPS-induced ALI. ISL  significantly alleviated ALI  in mice, inhibited reactive oxygen species (ROS) generation and cytotoxicity induced by t-BHP and pro-inflammatory enzymes production. ILG significantly inhibited LPS-induced lung histopathological changes. ILG inhibited the inflammatory of LPS-induced lung injury. GL can be used as a novel therapeutic strategy for pulmonary inflammation. Against  ALI and acute respiratory distress syndrome (ARDS). GL reduce lipopolysaccharide-induced acute lung injury. Significantly alleviated lung injury in LPS-induced ALI mice. GA significantly attenuated lung injury and decreased the production of inflammatory factors TNF-α, IL-1β, and high-mobility group box 1 HMGB1. Has protective effect on ALI in mice, inhibited  pro-inflammatory mRNA expression levels, and the tissue injury. GA has strong  hepatoprotective activity agent in hepatic infectious disease. GL suppress Epithelial-mesenchymal transition (EMT) that plays an important role in fibrosis, chronic inflammation of lung. The histolopathological lung injury was alleviated by combinational  more effectively inhibited neutrophilic airway inflammation . SKBHT suppresses inflammation in the lung.	The protective effects of GL may attribute partly to the suppression of COX-2 and iNOS expression. ISL activated AMPK/Nrf2/ARE signaling (survival pathway that alleviates oxidative injury) and inhibited LPS-induced NLRP3 and NF-κB activation in the lung(pro-inflammatory pathways that cause damage to cells). By activating PPAR-γ and inhibiting NF-κB activation. GL inhibited proinflammatory cytokines playing a key role in the initial phase of inflammatory response, through inhibition of the TLR-4/NF-κB signal pathway Glycyrrhizin inactivates toll-like receptor (TLR) signaling pathway and NF-κB pathway-related or it inhibiting TLR2 which essential for TLR activation. GL inhibited proinflammatory cytokines playing a key role in the initial phase of inflammatory response, through  inhibition of the TLR-4/NF-κB signal pathway GA inhibited the production of inflammatory factors and  regulates the PI3K/AKT/mTOR pathway related autophagy. Antiinflammatory and antioxidative stress. Not only by suppressing HMGB1 release and blocking HMGB1 cytokine activity, but also via  block an underlying viral-induced HMGB1-TLR4 immunological regulation axis that occurs during the cytokine storm. Gl  act by block Smad2/3 signaling pathway through inhibiting high-mobility group box1 (HMGB1). By regulating the expression of inflammatory cytokines and CXCL-2 by blocking the IL-17/STAT3 pathway. SKBHT suppressed NF-κB activity  and activating Nrf2 and TNFAIP3.	Ni et al., 2011 Liu et al., 2017 Zhang et al., 2018a Lee et al., 2019 Kong et al., 2019 Lee et al., 2019 Qu et al., 2019 Shen et al., 2020 Shi et al., 2020 Gui et al., 2020. Kim et al., 2020a Kim et al., 2020a