Alcohol-associated liver disease (ALD) is a prevalent chronic liver disease worldwide, with unclear pathogenesis and limited effective treatments. Mori Fructus polysaccharide (MFP-1) exhibits good therapeutic potential for ALD, but its mechanism remains unclear. This study aims to elucidate how MFP-1 mitigates ALD. An integrated multi-omics approach, encompassing quantitative proteomics, metabolomics, and lipidomics, was employed to systematically characterize the hepatic response to MFP-1 in ALD. MFP-1 coordinates metabolic reprogramming by regulating fatty acid synthesis and β-oxidation. It also enhances branched-chain amino acid catabolism via the 2-oxocarboxylic acid pathway, optimizing energy generation and amino acid utilization. MFP-1 protects against ALD by simultaneously targeting multiple metabolic vulnerabilities. These findings elucidate the mechanistic basis of MFP-1’s hepatoprotective effects and highlight its potential for improving ALD.

Alcoholic liver disease (ALD) has emerged as a critical global health concern. Dendrobium officinale polysaccharide (DOP) shows therapeutic potential against ALD. However, despite its promising effects, the protective mechanism of DOP on the ALD is unclear. To investigate the protective mechanisms of DOP, we successfully established an ethanol-induced liver injury model in mice and treated ALD mice with DOP. The results demonstrate that DOP treatment significantly reduced hepatic TG, TC, AST, ALT and MDA levels, while enhancing antioxidant capacity through elevated SOD, GST and GPx, reduced GSH and CAT activities. Mechanistically, DOP activates the KEAP1-Nrf2 signalling pathway, reduces the expression of Keap1, and simultaneously upregulates the expression of Nrf2 and its downstream target NQO1. Furthermore, DOP restored lipid homeostasis in ALD mice. In summary, these findings provide strong scientific evidence for the therapeutic potential of DOP in the treatment of ALD and establish a foundation for developing DOP based natural hepatoprotective agents.