Blackcurrant Extract Regulates Lipid Metabolism in <em>Caenorhabditis elegans via</em> 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 <em>vitro</em> and the high-glucose-fed <em>Caenorhabditis elegans</em> (<em>C. elegans</em>) in<em> vivo</em> by 46.06% and 56.68%. Additionally, the lifespan of <em>C. elegans</em> 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 (<em>sbp-1</em>,<em> fat-6</em>, and <em>fat-7</em>) were down-regulated by BCE, while genes in the NHR-49/PPARα pathway (<em>nhr-49</em>, <em>acs-2</em>, <em>ech-1.1</em>, and <em>cpt-2</em>) were up-regulated. Furthermore, Oil Red O staining and triglyceride (TG) content assays demonstrated that the hypolipidemic effect of BCE was absent in <em>nhr-49</em>, <em>fat-6</em>, and <em>fat-7</em> mutant strains of <em>C</em><em>. elegans</em>. The current findings were validated by molecular docking, indicating that abnormal fat accumulation in <em>C. elegans</em> 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.