Verbascoside from Callicarpa nudiflora Hook extends lifespan in Caenorhabditis elegans via SKN-1 pathway activation

Aging involves a progressive decline in physiological function, leading to organ damage and age-related chronic diseases. Natural products derived from traditional herbs represent a valuable resource for identifying anti-aging compounds and potential lead candidates. In this study, a screen of an herbal library using Caenorhabditis elegans (C. elegans) identified the 75% ethanol extract of Callicarpa nudiflora Hook (LWLY01) as a potent lifespan-extending agent. Further fractionation revealed that its ethyl acetate extract (LWLY03) exhibited significant anti-aging activity, albeit with complex composition. Through systematic isolation and identification, verbascoside was determined to be a key active constituent. Verbascoside extended the lifespan of C. elegans and improved healthspan parameters, including motility and resistance to osmotic and thermal stress. Mutant lifespan assays demonstrated that verbascoside acts through activation of the SKN-1 signaling pathway, thereby strengthening resistance to aging-associated oxidative stress. Additionally, verbascoside was found to regulate multiple aging-related processes, such as stress response, oxidative damage, and cellular homeostasis. These findings highlight verbascoside as a promising natural compound for mitigating aging phenotypes and preventing age-related diseases.