The potential mechanism of Isodon suzhouensisagainst COVID-19 via EGFR/TLR4 pathways

Abstract

Corona Virus Disease 2019 has brought the new challenges to scientific research. Isodon suzhouensis has good anti-inflammatory and antioxidant stress effects, which is considered as a potential treatment for COVID-19. The possibility for the treatment of COVID-19 with suzhouensis and its potential mechanism of action were explored by employing molecular docking and network pharmacology. Network pharmacology and molecular docking were used to screen drug targets, and Lipopolysaccharide (LPS) induced RAW264.7 and NR8383 cells inflammation model was used for experimental verification. Collectively a total of 209 possible linkages against 18 chemical components from suzhouensis and 1194 COVID-19 related targets were selected. Among these, 164 common targets were obtained from the intersection of suzhouensis and COVID-19. GO and KEGG enriched 582 function targets and 87 target proteins pathways, respectively. The results from molecular docking studies revealed that rutin, vitexin, isoquercitrin and quercetin had significant binding ability with SARS-CoV-23CLpro and ACE2. In vitro studies showed that Isodon suzhouensis extract (ISE) may inhibit the activation of PI3K/Akt pathway and the expression level of downstream pro-inflammatory factors by inhibiting the activation of EGFR in RAW264.7 cells induced by LPS. In addition, ISE was able to inhibit the activation of TLR4/NF-κB signaling pathway in NR8383 cells exposed to LPS. Overall, the network pharmacology and in vitro studies conclude that active components from suzhouensis have strong therapeutic potential against COVID-19 through multi-target, multi-pathway dimensions and can be a promising candidate against COVID-19.