Mechanistic insights into the therapeutic effects on liver fibrosis in Wilson's disease: a transcriptomic and network pharmacology-based approach.

BACKGROUND: The mechanism of the Bushen Huoxue Huazhuo Formula (BSHXHZF) in treating Wilson's disease (WD) liver fibrosis was investigated in this study using transcriptomics, network pharmacology, and molecular docking approaches. METHODS: Differentially expressed long non-coding RNAs (DELncRNAs) and messenger RNAs in the liver tissues of different groups were identified using high-throughput chip sequencing. Furthermore, the target genes of DELncRNAs were identified, followed by GO functional enrichment and KEGG pathway analyses. DELncRNAs were validated using quantitative reverse transcription-polymerase chain reaction. Active compounds of BSHXHZF and their associated pathways relevant to liver fibrosis treatment in WD, with initial validation via molecular docking. RESULTS: Transcriptomic analysis identified 63 DELncRNAs by comparing the control with the model and treatment groups. Key DELncRNAs included NONMMUT060008.2, NONMMUT096375.1, and ENSMUST00000153523. Target genes such as Pik3cd, Pld1, Oprd1, Ppp2r2b, and Cers5 were implicated in sphingolipid signaling, metabolism, and AMPK pathways. The "BSHXHZF-Component-Target" network highlighted active ingredients, including tanshinone IIA, quercetin, and luteolin, which play key roles in treating liver fibrosis. Main signaling pathways included IL-17, HIF-1, prolactin, and NF-κB. CONCLUSION: The therapeutic effects of BSHXHZF in liver fibrosis associated with WD are likely linked to its modulation of sphingolipid and IL-17 signaling pathways.