Eupatorium lindleyanum DC Ameliorates Carbon Tetrachloride-Induced Hepatic Inflammation and Fibrotic Response in Mice

<b>Background/Objectives:</b><i>Eupatorium lindleyanum</i> DC (Eup), a traditional Chinese medicinal herb, is widely used for treating inflammation-mediated diseases, including pneumonia. However, its potential therapeutic effects on inflammation-driven liver fibrosis remain to be elucidated. This study aimed to investigate the effects of Eup on carbon tetrachloride (CCl₄)-induced liver fibrosis and elucidate its underlying mechanisms. <b>Methods:</b> The chemical constituents of Eup were analyzed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-LC/MS). A CCl₄-induced liver fibrosis murine model and LX-2 cells were used in study. Serum biochemical assays, histological analysis, qRT-PCR, ELISA, and Western blot were used to assess Eup's anti-inflammatory and anti-fibrotic properties. RNA sequencing (RNA-seq) was employed to identify potential mechanisms, with validation by Western blot. <b>Results:</b> 89 and 49 compounds were identified in Eup under positive and negative ion modes, respectively. <i>In vivo</i>, Eup treatment decreased collagen deposition and expression levels of fibrosis-related genes, including collagen I and α-smooth muscle actin. Additionally, Eup alleviated hepatic inflammation. <i>In vitro</i>, Eup inhibited FBS-induced hepatic stellate cell (HSCs) activation. Gene set enrichment analysis (GSEA) indicated that Eup significantly downregulated the platelet-derived growth factor (PDGF)/platelet-derived growth factor receptor-beta (PDGFR-β) signaling pathway, which was further validated in both CCl₄-induced fibrotic livers and PDGF-BB-activated HSCs using western blot. <b>Conclusions:</b> Eup attenuated liver fibrosis by inhibiting inflammation and suppressing HSCs activation via downregulating PDGF/PDGFR-β signaling pathway.