Gandouling protects against hepatic fibrosis in Wilson disease through the lncRNA-SNHG7/miR-29b/DNMT3A pathway.

The therapeutic efficacy of Gandouling (GDL) against hepatic fibrosis, along with its underlying mechanisms, was evaluated in a model of Wilson disease (WD). Using a copper-loaded rat model and in vitro LX-2 cell assays, we comprehensively evaluated the effects of GDL by employing transmission electron microscopy (TEM), histopathology, ultrasound elastography, confocal microscopy (mCherry-GFP-LC3 assay), qRT-PCR, and Western blotting. GDL treatment significantly improved liver function, indicated by reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), laminin (LN), type III pre-collagen (PC-III), and collagen IV (C-IV). GDL also reduced the hepatic copper content and ameliorated histopathological and ultrasonographic signs of fibrosis. At the molecular level, GDL downregulated the expression of lncRNA SNHG7, DNMT3A, α-smooth muscle actin (α-SMA), and collagen I, while upregulating the expression of miR-29b. Furthermore, GDL inhibited autophagy, as shown by reduced levels of Beclin-1 and LC3-II/LC3-I and decreased autophagosome formation. These results demonstrate that GDL alleviates copper overload-induced hepatic fibrosis through modulation of the SNHG7/miR-29b/DNMT3A axis and inhibition of excessive autophagy.