Natural compound puerarin may protect against cholestatic liver fibrosis

A recent study published in Current Molecular Pharmacology demonstrates that puerarin-a bioactive isoflavone derived from Kudzu root and widely used in traditional Chinese medicine-may offer significant therapeutic benefits against cholestatic liver fibrosis, a progressive pathological condition arising from impaired bile formation and flow that currently lacks effective pharmacotherapies.

Researchers from Zhejiang University School of Medicine and collaborating institutions established a bile duct ligation-induced cholestatic liver fibrosis rat model and administered puerarin at 100 mg/kg/day for three weeks. The treatment significantly ameliorated serum biochemical abnormalities, including reductions in ALT, AST, ALP, γ-GT, total bilirubin, and direct bilirubin, while histological analysis revealed attenuated bile duct proliferation, diminished inflammatory cell infiltration, and decreased collagen deposition as confirmed by picrosirius red and Masson's trichrome staining.

Through integrative transcriptomic and metabolomic analyses, the team uncovered that puerarin modulates hepatic mRNA expression profiles with significant enrichment in extracellular matrix organization, focal adhesion, ECM-receptor interaction, and the PI3K-Akt signaling pathway-a central regulator of hepatic stellate cell activation and fibrogenesis. Metabolomic profiling further indicated that puerarin promotes the conjugation of hydrophobic bile acids into more hydrophilic forms, including GCDCA, TDCA, GDCA, and GCA, suggesting enhanced hepatic detoxification capacity. "Puerarin does not merely alleviate symptoms of liver damage but enhances the liver's intrinsic metabolic capacity to neutralize and eliminate cytotoxic substances," noted corresponding author Dr. Kunkai Su. In vitro experiments using HepaRG hepatocytes exposed to a bile acid mixture confirmed that puerarin attenuated hepatotoxicity and preserved cell proliferative capacity.

The findings position puerarin as a promising candidate therapeutic agent for cholestatic liver fibrosis, targeting both fibrotic pathways and bile acid homeostasis. However, the authors acknowledge that further studies are needed to fully elucidate its net protective effect on bile acid metabolism, with future research employing more clinically relevant models and comprehensive dose-response profiling.