Protective effect and mechanism of Perilla frutescens (L.) Britton on acute liver injury via an integrated strategy of pharmacodynamics, liver metabonomics and lipidomics, and network pharmacology

This study first compared the protective effects of different parts of Perilla frutescens (L.) Britton leaves (PFo), stems (PCa), and seeds (PFr) on LPS/ D-GalN-induced acute liver injury (ALI) in rats, to screen the most effective parts. The results indicated that PFo can effectively improve the histopathological changes of the liver, significantly reduce ALT, AST, LDH, TBil, TNF-α, and IL-1β levels, and increase GSH levels in ALI rats. Moreover, PFo inhibited apoptosis and ROS production in D-GalN-stimulated HepG 2 cells, and suppressed TNF-α and IL-6 production in LPS-elicited RAW 264.7 cells. Subsequently, based on the optimal results of PFo's anti-ALI effects, comprehensive analyses of liver metabonomics and lipidomics, and network pharmacology indicated that TNF, AKT1, ALB, STAT3, ESR1, EGFR, and PTGS2 might be the major targets for the anti-ALI of PFo, demonstrating that PFo exerts therapeutic properties against ALI might be related to suppressing oxidative stress, inflammation, and apoptosis.