Systems Pharmacology and GC-MS Metabolomics Reveal the Efficacy and Mechanisms of Zedoary Oil on Acute Liver Injury Induced by Oxidative Stress.

Background: Zedoray oil (ZO) is the main component of Curcuma zedoaria, one traditional herb used for dispersing stasis clinically in China. Previously, the potential of ZO was discovered against lethal and acute liver injury (ALI) mice with little impact on the immune, which deserved further study. Methods: An approach combined systems pharmacology with GC-MS metabolomics was applied for predicting pathways affected by ZO. Subsequently, H2O2 and tertbutyl hydroperoxide (t-BHP) were respectively applied to induce the ALI model in vitro for validation. Results: First, systems pharmacology and intracellular metabolites suggested that ZO might regulate oxidative stress via PI3K/Akt/FoxO1 pathway, TCA cycle, pantothenate, and CoA biosynthesis, beta-alanine metabolism, and propanoate metabolism. Further, levels of ALT, AST, ROS, T-AOC, MDA, GR, Delta psi m, and related proteins affected by ZO had been detected to validate the above mechanisms using dual cell models. Conclusion: ZO could protect the L02 cells against ALI by regulating the PI3K/Akt/FoxO1 pathway, as well as restore the function of mitochondria and redox imbalance damaged by toxicants. This work has uncovered the nonimmune mechanisms of ZO against ALI to provide the basis for relevant research and disease treatment.