Abstract
Objectives:Alpinia japonica (A. japonica) is traditionally used for digestive disorders, but its hypolipidemic mechanisms remain unclear. This study investigated the lipid-lowering effects of its fruit (SJGS), rhizome (SJGJ), and leaf (SJY) extracts, exploring their bioactive constituents and organ-specific mechanisms. Methods: Sprague Dawley rats (n = 8/group) fed a high-fat diet received SJGS, SJGJ, or SJY (200 mg/kg/day) for 4 weeks. Serum lipids (TC, TG), liver enzymes (AST, ALT), and intestinal barrier markers (DAO) were measured. Gut microbiota (16S rDNA sequencing), hepatic histopathology, and ileal tight junction proteins were analyzed. Transcriptomics and qPCR assessed ileal gene expression. LC-MS identified chemical constituents, while network pharmacology predicted compound-target interactions. Results: All extracts significantly reduced serum TC (↓ 27-33%), TG (↓ 29-38%), AST/ALT (↓ 22-30%), and DAO (↓ 35-42%) versus controls (p < 0.05). They improved hepatic steatosis, enhanced intestinal barrier function, and modulated gut microbiota (↑ α-diversity, ↓ Firmicutes/Bacteroidetes ratio). Transcriptomics revealed PPAR signaling as the core pathway: SJGS/SJGJ downregulated fatty acid oxidation genes (ACSL1, ACOX1, ACADM), while SJY upregulated APOA1 (2.3-fold). LC-MS identified 33-48 compounds/part, with seven shared constituents. Network analysis prioritized three flavonoids (pinocembrin, luteolin, galangin) targeting TNF, AKT1, and PPAR pathways. Conclusions: The findings suggest A. japonica extracts ameliorate hyperlipidemia through distinct mechanisms-SJGS/SJGJ may inhibit fatty acid oxidation, while SJY potentially enhances APOA1-mediated clearance. Shared flavonoids likely contribute to these effects via PPAR signaling, supporting its traditional use. This study provides a scientific basis for the sustainable utilization of A. japonica resources.