Pharmacodynamic effects and mechanism of Pueraria lobata-Schisandra chinensis combination in the treatment of alcoholic liver disease

With the increasing consumption of alcohol and alcoholic beverages, liver injury may occur. This has become an important cause endangering human health. As edible herbal medicines, Pueraria lobata (PL) and Schisandra chinensis (SC) are often used in combination to treat alcohol-related diseases and have a long-standing history in China. In this study, we demonstrated that the PL-SC drug pair (PS) could mitigate ethanol-induced liver injury through the construction of both in – vivo and in - vitro models. Pharmacodynamic results showed that PS attenuated liver injury by lowering aspartate aminotransferase (AST) and alanine aminotransferase (ALT). It increases alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) levels and relieves alcohol-suppressed nervous system excitability. PS is more effective compared to PL or SC alone. The chemical components of the PS combination were identified using UPLC-Q-TOF-MS. By integrating transcriptome sequencing, network pharmacology, and molecular docking techniques, it was discovered that Puerarin, Daidzein, Schisandrol A, and Schisandrin A in PS could act on key targets in the PI3K/AKT pathway, thus treating ALD. Metabolomic analysis revealed that dysregulation of Arachidonic acid (AA) metabolic pathways exacerbated inflammatory responses and oxidative stress, subsequently mediating pathological changes in ALD and exacerbating liver damage.