Phelligrin B, a flavonoid compound from Sanghuangporus vaninii, improves CCl4-induced acute liver injury associated with the PI3K-AKT1-mTOR pathway.

Acute liver injury (ALI) is a severe condition with high risk of progression to liver failure. Traditional Chinese Medicine plays an important role in liver protection. This study aimed to investigate the protective effects and mechanism of Sanghuangporus vaninii against ALI. Network pharmacology identified active components and their potential targets. Molecular docking and dynamics simulations validated the binding interactions between active components and key targets. In vivo CCl4-induced ALI mice were pretreated with Phelligrin B to assess liver pathology, function, oxidative stress, inflammation, and PI3K-AKT1-mTOR pathway expression. In vitro CCl4-injured hepatocytes were treated with Phelligrin B to evaluate viability, LDH release, oxidative stress, inflammation, and the PI3K-AKT1-mTOR pathway activation. Results showed that 15 active flavonoids were identified from Sanghuangporus vaninii, sharing 137 common targets with ALI, among which AKT1 was the most significant. Molecular docking analysis of the main active components with AKT1 revealed Phelligrin B as the compound with the highest binding affinity. Further molecular dynamics simulations confirmed a stable binding mode. In vivo studies demonstrated that Phelligrin B significantly alleviated liver injury, oxidative stress, and inflammation in the ALI mouse model. And Phelligrin B notably suppressed AKT1 protein expression and inhibited the activation of the PI3K-AKT1-mTOR pathway. Similarly, in vitro, Phelligrin B counteracted CCl4-induced reductions in cell viability and increases in LDH release, mitigated oxidative stress and inflammatory responses, and suppressed the activation of the PI3K-AKT1-mTOR pathway in the cellular model. In conclusion, Phelligrin B, the flavonoid (specifically, a dihydroflavone derivative) from Sanghuangporus vaninii alleviates CCl4-induced ALI, an effect associated with inhibition of the PI3K-AKT1-mTOR pathway.