Hepatoprotective Effect of Morchella Mycelia Polysaccharides on Alcoholic Liver Injury and Its Mechanism Involving the Modulation of NOD ‐Like Receptor Signaling Pathway

ABSTRACT Alcoholic liver disease (ALD) is one of the leading causes of preventable liver‐related morbidity and mortality globally. Bioactive polysaccharides exhibit substantial potential as functional foods and therapeutic agents for the prevention and treatment of alcoholic liver injury (ALI). Morchella , an edible and medicinal fungus, contains polysaccharides with diverse biological activities. This study aimed to evaluate the protective effects of Morchella mycelium polysaccharides (MP) against alcohol‐induced liver injury and elucidate the underlying mechanisms. The MP was isolated from the Morchella mycelium using water extraction–ethanol precipitation. Its primary component was glucose (96.555%), with a weight‐average molecular weight of 5.7 kDa and an α‐glycosidic configuration. These characteristics indicated a highly homogeneous polysaccharide structure. Research findings demonstrated that the MP significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, improved lipid metabolism (evidenced by decreased triglyceride and cholesterol levels), and restored the histopathological structure of the mouse liver. Mechanistically, the MP alleviated oxidative stress by enhancing the activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione) and inhibiting lipid peroxidation (indicated by reduced malondialdehyde levels). Transcriptomic analysis further revealed the anti‐inflammatory mechanism of MP. It downregulated the expression of Ifi16 , Pycard , and Nlrp3 by suppressing the Nlrp3 inflammasome in the NOD‐like receptor signaling pathway. This suppression subsequently inhibited pro‐Casp1 activation and the pyroptosis of hepatocytes. Additionally, the MP upregulated the antimicrobial peptide Camp , highlighting its dual functions in anti‐inflammation and intestinal barrier protection. Collectively, these results suggest that Morchella mycelia polysaccharide, as a potent natural compound, holds significant promise for combating alcohol‐induced liver injury.