Prunus mongolica oil attenuates hepatic fibrosis via 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 Prunus mongolica 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 (P = 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 via the Gck/rno-miR-667-5p/Cyp8b1 axis, providing a theoretical foundation for developing multitarget phytopharmaceuticals against liver fibrosis.