Flavonoids from Radix Puerariae Alleviated Alcoholic Liver Disease via PI3K/AKT Signaling Pathway

Alcoholic Liver Disease (ALD) represents a spectrum of hepatic disorders resulting from chronic excessive alcohol consumption. Radix Puerariae, the dried root of Pueraria Lobata (Willd.) Ohwi has been traditionally used to both counteract alcohol toxicity and protect the liver. Flavonoids, including puerarin, daidzein, and genistein, are the main bioactive components of Radix Puerariae. However, their specific mechanisms of action against ALD remain unclear. In this study, we therefore evaluated the hepatoprotective effects of the flavonoid from Radix Puerariae (FRP) using both in vitro and in vivo ALD models, and assessed the extent of pathological damage using Hematoxylin-Eosin (HE) staining. The relevant assay kits were used to measure inflammatory responses and oxidative stress-related indicators. In addition, a combination of metabolomics and network pharmacology was used to elucidate the PI3K/AKT signaling pathway as a potential mechanism of FRP-based ALD treatment. Western blotting experiments were conducted to measure the expression levels of key proteins, and the pharmacodynamic results showed that FRP reduced liver injury. Metabolomics revealed that FRP significantly regulated the levels of 73 metabolites involving the glycerophospholipid metabolism, arachidonic acid metabolism, and alpha-linolenic acid metabolism pathways. Network pharmacology results suggested that INS, AKT1, and TNF may be potential targets, and Western blot experiments showed that FRP could alleviate ALD by activating the PI3K/AKT pathway. These results indicated that FRP could exert its therapeutic effect against ALD by regulating the PI3K/AKT signaling pathway, and establish a robust application foundation for further research.