Physicochemical characterization, lipid-modulating effects, and proteomic insights of Malaysian Sacha Inchi (Plukenetia volubilis L.) seed oil in HepG2 cells

Abstract

Sacha Inchi (SI) (Plukenetia volubilis L.) is recognized for its health benefits, especially in lipid modulation. However, its effects on lipid-metabolizing pathways at the proteomic level, particularly in hepatic models like HepG2 cells, remain underexplored. This study investigated the lipid-modulating effects of Malaysian SI seed oil on oleic acid (OA)-induced HepG2 cells, utilizing physicochemical characterization, lipid accumulation assays, proteomics, and pathway analysis. The physicochemical analysis confirmed its oxidative stability and a favorable omega-3/omega-6 ratio, supporting its nutritional potential. Oil Red O staining demonstrated concentration-dependent reductions in OA-induced lipid accumulation, with 20 μL/mL SI oil achieving efficacy comparable to atorvastatin. Proteomic and pathway analyses revealed significant modulation of key proteins (VDAC3, ALDH9A1, SOD2, GSTK1, and ACAT1) associated with lipid-related pathways. Fatty acid degradation exhibited the highest fold enrichment (48-fold, p < 0.001), while peroxisome, ferroptosis, and fat digestion/absorption pathways were also significantly enriched. These findings suggested that SI oil modulated lipid metabolism through several key lipid-related pathways, highlighting its potential as a therapeutic agent for regulating metabolism and promoting liver health. Further in vivo and clinical studies are needed to validate its therapeutic potential.