Objective: To explore the mechanism of liver injury induced by Dictamni Cortex water extract through interference with lipid metabolism in the liver.Methods: Thirty - two SPF - grade male SD rats were randomly divided into four groups: control group, high - dose Dictamni Cortex group (8.1 g/kg), medium - dose group (2.7 g/kg), and low - dose group (0.9 g/kg), with 8 rats in each group. The rats were administered by gavage for 8 weeks. Liver weight, liver - to - body weight ratio, and liver toxicity - related indicators were measured to observe changes in the rats' liver. Hematoxylin - eosin (HE) staining and Oil Red O staining were used to assess the pathological changes and lipid droplet accumulation in liver tissues. The mRNA levels of AMPK, PPAR - α, IL - 1β, and TNF - α were detected in liver tissues. Lipid levels in the liver were analyzed by LC - MS/MS, and multivariate statistical analysis was used to identify differentially expressed lipid metabolites.Results: Compared with the control group, the liver - to - body weight ratio was increased in all Dictamni Cortex dose groups(P < 0.01, P < 0.001). In the high - dose group, AST、ALT、ALB levels were significantly increased (P < 0.05, P < 0.001). HE and Oil Red O staining showed that the high - dose group significantly induced fatty liver lesions in rats. The mRNA levels of inflammatory factors IL - 1β and TNF- α were significantly increased (P < 0.01), while the mRNA levels of PPAR - α, were significantly reduced (P <0.01). Lipidomics analysis showed that, compared to the control group, 156 lipid species were significantly altered in the high - dose group, including glycerolipids, phosphatidylcholine, sphingolipids, etc. Specific lipids such as PC(16∶0/18∶2), PC(16∶0/18∶1)、PC(14∶0/18∶2)、PC(15∶0/18∶2)、TG(16∶0/16∶0/16∶0), TG(18∶0/16∶0/16∶0)、SM(d42∶1), SM (d42∶2), SM (d42∶3) showed significantly variation levels after treatment. These results suggest that the high - dose Dictamni Cortex water extract disturbed lipid metabolism in the liver of rats.Conclusion: The water extract of Dictamni Cortex induces liver injury in rats by interfering with lipid metabolism, particularly sphingolipids (SM), ceramides (Cer), triglycerides (TG), and phosphatidylcholine (PC).

Dictamni Cortex  /  Lipidomics  /  Liver injury