Oridonin inhibits SGIV infection by regulating glycolipid metabolism and inflammatory response

Singapore grouper iridovirus (SGIV) is a significant infectious disease in the grouper aquaculture industry. Currently, there is no effective drug available to prevent or treat SGIV. Oridonin (Ori) is a naturally occurring compound derived from Rabdosia rubescens, exhibiting various biological activities, including anti-tumor, anti-inflammatory, and antioxidant properties. In this study, we examined the anti-SGIV activity of Ori and its potential mechanism of action in vitro. The study results indicate that Ori effectively inhibits SGIV infection at various concentrations. Further studies reveal that Ori inhibits the formation of lipid droplets induced by SGIV infection. Additionally, Ori suppresses the SGIV-induced up-regulation of fatty acid synthesis-related genes (SREBP1, ACC1, SCD1, FASN) and glycolysis-related genes (GLUT1, GLUT2, HK2, PDHX). The mTOR pathway plays a crucial role in regulating glycolipid metabolism. Our findings indicate that Ori suppresses the phosphorylation of AKT and mTOR proteins. Further research revealed that the activation or inhibition of mTOR significantly impacts SGIV protein production and the expression of genes related to glycolipid metabolism. In addition, Ori effectively inhibits the up-regulation of NLRP3, ASC, Caspase-1, and pro-inflammatory cytokines induced by SGIV infection. In conclusion, our experimental findings indicate that Ori effectively inhibits SGIV infection by regulating glycolipid metabolism through the AKT/mTOR pathway and by suppressing the inflammatory responses triggered by SGIV infection.