Yixingensin Extends Lifespan and Modulates Stress-Response and Lipid-Metabolism Programs in Caenorhabditis elegans

Yixingensin (ombuin-3-O-glucoside) is a flavonoid glycoside previously reported to activate peroxisome proliferator-activated receptors in mammalian cells. Whether it affects lifespan in vivo remains unclear. In the present study, the effects of yixingensin were evaluated in wild-type Caenorhabditis elegans using bacterial growth assays, lifespan and healthspan phenotyping, a high-glucose-induced lipid accumulation model, transcriptome sequencing, and qRT-PCR validation. Yixingensin (25~100 μM) did not inhibit the growth of Escherichia coli OP50. Treatment with yixingensin significantly extended the mean lifespan of C. elegans without adversely affecting general physiological parameters and, at selected concentrations, improved pharyngeal pumping and body-bending activity. Yixingensin also reduced high-glucose-induced triglyceride accumulation. Consistently, imaging analyses revealed decreased lipofuscin autofluorescence and Oil Red O staining following yixingensin treatment. RNA sequencing identified 4677 differentially expressed genes, including 1313 upregulated and 3364 downregulated genes. These genes were significantly enriched in pathways related to xenobiotic metabolism, fatty acid metabolism, glutathione metabolism, and longevity regulation in C. elegans. qRT-PCR validation further showed that the stress-responsive genes hsp-12.3, hsp-16.2, and mtl-1 were upregulated, whereas sod-3 expression was downregulated. Overall, yixingensin treatment was associated with lifespan extension and remodeling of metabolic and stress-response gene programs.