Discovery of p-Coumaric Acid as a Candidate Cholesterol-Lowering Factor in Germinated Brown Rice via Untargeted Metabolomics Combined with a Cholesterol-Induced HepG2 Cell Model

Hypercholesterolemia is a major modifiable risk factor for cardiovascular disease. Although germinated brown rice (GBR) is rich in bioactive constituents and has shown preliminary lipid-regulating potential, the active compounds and underlying mechanisms remain unclear. Therefore, this study comparatively investigated extracts from four GBR cultivars and evaluated their cholesterol-regulating activity using untargeted metabolomics in combination with a cholesterol-induced HepG2 cell model. After 36 h of germination, the extracts showed significantly increased total phenolic content, total flavonoid content, and antioxidant activities (p < 0.05), with cultivar Q showing the strongest response. In the in vitro cholesterol-induced HepG2 cell model, GBR extract at 150 μg/mL significantly reduced intracellular total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels by approximately 69%, 73%, and 46%, respectively, while increasing high-density lipoprotein cholesterol (HDL-C) levels by approximately 125% (all p < 0.05). Untargeted metabolomics and subsequent validation suggested that p-coumaric acid is a candidate bioactive compound contributing to the cholesterol-lowering effect of GBR. Further analysis indicated that this effect may be associated with modulation of the mRNA expression levels of SREBP2, HMGCR, and LDLR. These findings indicate that germination enhances the bioactivity of brown rice in a cultivar-dependent manner and provides supporting evidence for the potential application of GBR as a functional food ingredient for lipid management.