Genistein combined with aerobic exercise protects against alcoholic liver injury through PI3K/AKT/GSK3β signaling.

Alcoholic liver injury is a common liver disease worldwide. Currently, there is a lack of safe and effective comprehensive intervention methods. In this study, the intervention effect and mechanism of aerobic exercise combined with genistein on alcoholic liver injury were explored. By establishing the rat model of alcoholic liver injury, we found that the combined intervention could significantly improve liver function, regulate blood lipids and enhance ethanol metabolism. Meanwhile, aerobic exercise combined with genistein can effectively alleviate oxidative stress and inhibit inflammatory responses. Liver histopathological examination confirmed that the combined treatment could significantly alleviate liver injury, inflammatory infiltration and fibrosis. Network pharmacology and molecular docking suggested that the PI3K/AKT/GSK3b pathway was the core target. Western blot experiments further confirmed that the combined intervention could effectively regulate the PI3K/AKT pathway, inhibit GSK3b activity, and down-regulate the key lipid synthesis factor SREBF1. In conclusion, aerobic exercise combined with genistein had a synergistic effect in alleviating alcoholic liver injury. The mechanism may be closely related to the regulation of the PI3K/AKT/GSK3b signaling pathway, which in turn improves lipid metabolism, oxidative stress and inflammation.