Metabolomics uncovers Rubus idaeus-mediated recovery of energy and arginine metabolism in liver injury

The global incidence of acute liver injury continues to rise, posing a significant threat to public health. While both raw and processed Rubus idaeus Linnaeus (RI) demonstrate hepatoprotective properties, their mechanisms require further elucidation. This study employed UPLC-Q-TOF/MS-based serum metabolomics to delineate the distinct liver-protective mechanisms of raw and processed RI in a murine model of acute liver injury. Following ten days of intragastric administration with low, medium, and high doses of raw and processed RI extracts, mice received intraperitoneal injection of 50 % carbon tetrachloride in olive oil. Serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), as well as liver levels of superoxide dismutase (SOD), malondialdehyde (MDA), and hydroxyproline (Hyp), were measured via ELISA. Liver histopathology was examined using Hematoxylin and Eosin (HE), Masson, and Sirius Red staining. Treatment with both raw and processed RI significantly reduced serum AST, ALT, and ALP levels while decreasing hepatic MDA and Hyp content compared to the model group. Conversely, SOD activity showed marked elevation. Metabolomic profiling identified 39 significantly altered endogenous metabolites in the model group, with subsequent characterization of 22, 23, and 7 distinctive biomarkers in the raw, salt-processed, and wine-processed RI treatment groups, respectively. These biomarkers predominantly associated with energy metabolism and arginine metabolism. Furthermore, the phenolic and flavonoid compounds in RI, known for their anti-inflammatory and antioxidant properties, played a key role in mitigating liver damage induced by CCl₄. These findings provide strong evidence supporting the potential use of both raw and processed RI in the development of hepatoprotective health products.