Background
Excess alcohol exposure leads to alcoholic liver disease (ALD). Pueraria lobata (PUE) and Silybum marianum (SIL) are two well-known hepatoprotective herbal remedies with various activities. The possible effect of combination of PUE and SIL on ALD has not been elucidated yet.

Purpose
We aimed to demonstrate that the combination of PUE and SIL prevents against alcoholic liver injury in mice using a model of chronic-plus-single-binge ethanol feeding.

Study design
Male C57BL/6 mice were randomly divided into five groups (n = 8–10), namely the control group (CON), ethanol-induced liver injury group (ETH), 150 mg/kg PUE treated group (PUE), 60 mg/kg SIL treated group (SIL), 210 mg/kg PUE+SIL treatment group (PUE+SIL). Except control group, all animals were fed a modified Lieber-DeCarli ethanol liquid diet for 10 days. While, control group received Lieber-DeCarli control diet containing isocaloric maltose dextrin substituted for ethanol. On day 11, the mice orally received a single dose of 31.5% (v/v) ethanol (5 g/kg BW) or an isocaloric maltose solution.

Results
Ethanol exposure caused liver injury, as demonstrated by remarkably increased plasma parameters, histopathological changes, the increased lipid accumulation, oxidative stress and inflammation in liver. These alterations were ameliorated by the treatments of PUE, SIL and PUE+SIL. While, the PUE+SIL treatment showed the most effective protection, which was associated with reducing alcohol-induced hepatic steatosis via upregulating LKB1/AMPK/ACC signaling, and inhibiting hepatic inflammation via LPS-triggered TLR4-mediated NF-κB signaling pathway. Our results also indicated that the hepatoprotective effects of SIL+PUE might mainly attribute to the protection of SIL and PUE alone in alcohol-induced hepatic steatosis and hepatic inflammation, respectively.

Conclusion
These findings also suggest that the combination of PUE and SIL has a potential to be developed as a functional food for the management of ALD.