<i>Prunus mongolica</i> oil attenuates hepatic fibrosis <i>via</i> a lncRNA-mediated ceRNA network targeting dual PGC-1α/PPARγ and TGF-β/Smad3 pathways

Hepatic fibrosis (HF), a reversible yet critical pathological stage in chronic liver disease progression, represents a major global public health challenge. This study systematically investigated the antifibrotic mechanism of <i>Prunus mongolica</i> oil (OIL), an active component derived from traditional medicinal plants, through an integrated approach combining pharmacodynamics, transcriptomics, and molecular biology in carbon tetrachloride (CCl₄)-induced Sprague-Dawley rat models. Dose-response evaluation revealed optimal antifibrotic efficacy at the medium dosage (5 g kg^-1) compared with other concentrations (2.5 and 7.5 g kg^-1). Transcriptomic profiling identified 1734 differentially expressed mRNAs, 121 lncRNAs, and 82 miRNAs among model (MOD), control (CON), and OIL-treated groups. Construction of competing endogenous RNA (ceRNA) networks and functional enrichment analysis highlighted the potential association of the PPAR signaling pathway (<i>P</i> = 0.012, FDR = 0.27). Topological assessment using Cytoscape (v3.9.1) and the STRING database identified the Gck/rno-miR-667-5p/Cyp8b1 axis as the central regulatory node. Mechanistically, OIL exerted dual therapeutic effects: (1) upregulating PGC-1α/PPARγ expression to enhance metabolic reprogramming, and (2) suppressing TGF-β/Smad3 phosphorylation activation, thereby inhibiting hepatic stellate cell (HSC) activation and extracellular matrix (ECM) deposition. Immunohistochemical and western blot analyses validated these protein-level modulations. Our findings revealed a novel ceRNA-network-mediated mechanism wherein OIL attenuates hepatic fibrosis through coordinated regulation of PPAR and TGF-β/Smad3 pathways <i>via</i> the Gck/rno-miR-667-5p/Cyp8b1 axis, providing a theoretical foundation for developing multitarget phytopharmaceuticals against liver fibrosis.