Abstract Background Liver injury represents a major global health concern, and effective hepatoprotective agents remain urgently needed. This study investigated the hepatoprotective effects of Amygdalus mongolica oil in a carbon tetrachloride (CCl₄)-induced liver injury model, focusing on two complementary aspects: regulation of the PI3K/AKT/mTOR signaling pathway and modulation of the gut microbiota. Results A. mongolica oil exerted hepatoprotective effects at all doses tested, with the medium-dose group (OIL-M) showing the greatest overall efficacy. OIL-M attenuated hepatocyte necrosis, inflammatory cell infiltration, and collagen deposition, and improved serum liver function indices, fibrosis-related markers, and inflammatory cytokines. Western blot analysis showed that OIL-M inhibited aberrant activation of the hepatic PI3K/AKT/mTOR pathway, as reflected by reduced p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR ratios. OIL-M also restored gut microbial alpha and beta diversity, shifting the overall community structure toward that of the control group (CON). Linear discriminant analysis effect size (LEfSe) identified ten discriminatory taxa enriched in the OIL-M group, including Dorea , Psychrobacter , Tuzzerella , Oscillibacter , Oligella , HT002, Colidextribacter , Roseburia , Anaerostipes , and Dubosiella . Genus-level analysis showed that OIL-M increased the relative abundances of Roseburia , Anaerostipes , Dubosiella , and Oscillibacter , while reducing Desulfovibrio . Spearman correlation analysis linked microbiota remodeling to improved hepatic phenotypes. PICRUSt2-based functional prediction indicated that OIL-M altered microbial metabolic potential, particularly in pathways related to nicotinate and nicotinamide metabolism and xenobiotic degradation. Conclusions These findings suggest that A. mongolica oil alleviates CCl 4 -induced liver injury through gut microbiota remodeling and inhibition of hepatic PI3K/AKT/mTOR signaling, providing evidence for the involvement of the gut-liver axis. Graphical Abstract Proposed schematic illustrating the mechanisms potentially involved in the protective effects of Amygdalus mongolica oil against CCl 4 -induced liver injury. A. mongolica oil may exert hepatoprotective effects by modulating the gut microbiota, characterized by increased relative abundances of Dubosiella , Anaerostipes , Roseburia , and Oscillibacter and a decreased abundance of Desulfovibrio , and by suppressing hepatic PI3K/AKT/mTOR signaling, as reflected by reduced p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR ratios. These coordinated changes were associated with the amelioration of liver injury.
Yan et al. (Thu,) studied this question.