Longchai Decoction Treated the Fibrosis of Liver Induced by CCl4 Regulates Nrf2/GPX4 Pathway to Suppress Ferroptosis.

The aim of the study is to evaluate the therapeutic efficacy of Longchai Decoction (LCD), an empirical traditional Chinese medicine formula for liver disorders, on liver fibrosis (LF) and to elucidate its molecular mechanisms. A mouse model of LF and an erastin-induced ferroptosis model was established in LX-2 cells, which were then treated with silybin and LCD. The therapeutic function of LCD on liver fibrosis was evaluated using biochemical assays, histopathological staining, transmission electron microscopy, transcriptome sequencing, and immunohistochemistry. The mechanisms by which LCD alleviated LF were investigated using western blotting and immunofluorescence. LCD treatment significantly decreased the serum concentrations of IL-1β, IL-6, and TNF-α. It also effectively suppressed lipid peroxidation, diminished iron accumulation, and preserved mitochondrial integrity within hepatic tissues. Transcriptome sequencing analysis revealed that LCD significantly increased the levels of genes including NRF2, GPX4, and HO-1, thereby modulating the Nrf2/GPX4 pathway both in vivo and in vitro, thereby inhibiting lipid peroxidation and ferroptosis. Our findings suggest that LCD plays a protective role against hepatocyte ferroptosis and mitigates CCl4-induced liver damage and fibrosis through the activation of the Nrf2/GPX4 pathway.