Soyasaponin Ba Alleviates Lipid Accumulation via Mitochondrial Remodeling: Multiomics Insights

Lipid accumulation is caused by obesity and related metabolic syndrome. This study aimed to explore how soyasaponin Ba improves lipid accumulation and reveals its molecular mechanism through multiomics and multi-in vitro and in vivo models. THLE-2 cells, HepG2 cells, and <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) were utilized to simulate lipid accumulation and study the effects and mechanisms of soyasaponin Ba from multiple perspectives including network pharmacology, transcriptomics, bioinformatics, and spatial metabolomics. Further experiments found that soyasaponin Ba improved phenotypes including lipid accumulation, reactive oxygen species generation, decreased mitochondrial membrane potential and morphological abnormality, and apoptosis in HepG2 and THLE-2 cell lines, which is achieved through targeting Akt and the Akt/GSK3β/β-catenin signaling pathway. The improving effect of soyasaponin Ba on lipid accumulation was also validated in the <i>C. elegans</i> model. Our findings provide a comprehensive viewpoint about the mechanisms of soyasaponin Ba in improving lipid accumulation, providing valuable guidance for further clinical application.