As a natural active substance,
dihydromyricetin (DHM) has been proven to have good hepatoprotective activity. However, the
therapeutic effect of DHM on
liver fibrosis, which has become a
liver disease threatening the health of people around the world, has not been studied to date. The purpose of this study was to investigate the effect of DHM as a new nutritional supplement on
thioacetamide (TAA)-induced
liver fibrosis. The
liver fibrosis model was established by
intraperitoneal injection of TAA (200 mg/kg, every 3 days) for 8 weeks, and
oral administration of DHM (20 mg/kg and 40 mg/kg, daily) after 4 weeks of TAA-induced
liver fibrosis. The results showed that DHM treatment significantly inhibited the activities of
alanine aminotransferase (ALT) (37.81 ± 7.62 U/L) and
aspartate aminotransferase (AST) (55.18 ± 10.94 U/L) in serum of
liver fibrosis mice, and increased the levels of
superoxide dismutase (SOD) and
glutathione (GSH) while reversed the level of
malondialdehyde (MDA). In addition, histopathological examination illustrated that TAA induced the inflammatory infiltration, apoptosis and fibroatherosclerotic deposition in liver, which was further confirmed by western-blot and immunofluorescence staining. Moreover, DHM inhibited hepatocyte apoptosis by regulating the phosphorylation level of
phosphatidylinositol 3-kinase (PI3K),
protein kinase-B (AKT) and its downstream apoptotic
protein family. Interestingly, immunofluorescence staining showed that DHM treatment significantly inhibited alpha smooth muscle actin (α-SMA), which was a marker of hepatic stellate cell activation, and regulated the expression of
transforming growth factor (TGF-β1). Importantly, supplementation with DHM significantly inhibited the release of
nuclear factor kappa-B (NF-κB) signaling pathway and pro-inflammatory factors in liver tissue induced by TAA, and improved liver fiber diseases, such as
tumor necrosis factor alpha (TNF-α) and recombinant rat IL-1β (IL-1β). In conclusion, the evidence of this study revealed that DHM is a potential hepatoprotective and health factor, and which also provides the possibility for the treatment of
liver fibrosis.