Mechanism of ligustrazine in alleviating biliary atresia-associated liver fibrosis by regulating the TGF-/Smad pathway and inhibiting hepatocyte pyroptosis

Key Points

• This research investigates the role of ligustrazine in alleviating liver fibrosis linked to biliary atresia by modulating the TGF-beta/Smad pathway and inhibiting hepatocyte pyroptosis.
• Conducted animal experiments with C57BL/6 mice divided into treatment groups over 14 days.
• Performed histological assessments and biochemical analyses including serum AST, ALT, and Western blot for various proteins associated with fibrosis and inflammation.
• Developed an in vitro model with HSC-T6 cells treated with TGF-beta1, followed by ligustrazine administration to assess cellular changes and signal pathways.
• The model group exhibited significant liver fibrosis, cell necrosis, and increased collagen deposition, along with elevated AST and ALT levels (P<0.001).
• Key proteins related to pyroptosis and inflammation, such as ASC and NLRP3, showed a marked increase (P<0.001; P<0.0001), while TGF-beta signaling proteins displayed significant alterations after treatment.
• Ligustrazine treatment effectively reversed fibrosis and corrected the dysregulated TGF-beta/Smad pathway, with consistent results in both animal and cellular models.