Blackcurrant Extract Regulates Lipid Metabolism in Caenorhabditis elegans via SBP-1 and NHR-49

Blackcurrant extract (BCE), rich in anthocyanins, has demonstrated significant potential in lipid level reduction. In this study, network pharmacology was applied to predict the lipid-lowering metabolic mechanism of BCE. Upon treatment with BCE (100 μg/mL), lipid accumulation was significantly reduced in both the HepG2 cells in vitro and the high-glucose-fed Caenorhabditis elegans (C. elegans) in vivo by 46.06% and 56.68%. Additionally, the lifespan of C. elegans was significantly prolonged by BCE treatment, its stress tolerance and antioxidant capacity were enhanced, and aging-related markers (e.g., lipofuscin accumulation) were altered. Subsequent qPCR analysis revealed that genes associated with the SBP-1/SREBP pathway (sbp-1, fat-6, and fat-7) were down-regulated by BCE, while genes in the NHR-49/PPARα pathway (nhr-49, acs-2, ech-1.1, and cpt-2) were up-regulated. Furthermore, Oil Red O staining and triglyceride (TG) content assays demonstrated that the hypolipidemic effect of BCE was absent in nhr-49, fat-6, and fat-7 mutant strains of C. elegans. The current findings were validated by molecular docking, indicating that abnormal fat accumulation in C. elegans was alleviated by BCE treatment via the SBP-1 and NHR-49 pathways. In summary, these findings indicated that BCE exerted a lipid-lowering effect and provided novel insights and research materials for the development of natural lipid-lowering medications and health products.