Mulberry Leaf Alkaloids and Their Main Component 1-Deoxynojirimycin Mitigate CDAHFD-Induced Metabolic Dysfunction-Associated Steatohepatitis by Promoting Autophagy through the PI3K/AKT/mTOR Pathway.

Chen Yang,Feng Xiang,Zhiqiang He,Yan Lin,Yuexin Liu,Yingyan Liao,Li-mei Lin,Qiuxian Peng

Published 2026 in Journal of Agricultural and Food Chemistry

ABSTRACT

Alkaloid components derived from mulberry leaves exhibit regulatory potential for liver lipid metabolism abnormalities, oxidative stress, and inflammatory responses. Among these components, 1-Deoxynojirimycin (DNJ), the primary alkaloid compound, has various biological activities. This study focuses on exploring the hepatoprotective effects and potential mechanisms of mulberry leaf alkaloids (MLA) and DNJ on MASH. The results showed that MLA and DNJ can significantly improve the pathological changes in liver tissue induced by a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD), alleviating liver injury, steatosis, inflammation, and fibrosis in MASH mice. Subsequent research has indicated that this protective effect is associated with the inhibition of the PI3K/AKT/mTOR pathway and the activation of the expression of liver autophagy-related proteins. Additionally, molecular docking analysis and molecular dynamics simulation demonstrated that DNJ exhibited a good binding affinity with PI3K, AKT, and mTOR. In conclusion, DNJ promotes autophagy through the PI3K/AKT/mTOR pathway, thereby alleviating MASH symptoms and fibrosis in mice.

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