2-Butoxytetrahydrofuran and Palmitic Acid from Holothuria scabra Enhance C. elegans Lifespan and Healthspan via DAF-16/FOXO and SKN-1/NRF2 Signaling Pathways

Extracts from a sea cucumber, Holothuria scabra, have been shown to exhibit various pharmacological properties including anti-oxidation, anti-aging, anti-cancer, and anti-neurodegeneration. Furthermore, certain purified compounds from H. scabra displayed neuroprotective effects against Parkinson's and Alzheimer's diseases. Therefore, in the present study, we further examined the anti-aging activity of purified H. scabra compounds in a Caenorhabditis elegans model. Five compounds were isolated from ethyl acetate and butanol fractions of the body wall of H. scabra and characterized as diterpene glycosides (holothuria A and B), palmitic acid, bis (2-ethylhexyl) phthalate (DEHP), and 2-butoxytetrahydrofuran (2-BTHF). Longevity assays revealed that 2-BTHF and palmitic acid could significantly extend lifespan of wild type C. elegans. Moreover, 2-BTHF and palmitic acid were able to enhance resistance to paraquat-induced oxidative stress and thermal stress. By testing the compounds' effects on longevity pathways, it was shown that 2-BTHF and palmitic acid could not extend lifespans of daf-16, age-1, sir-2.1, jnk-1, and skn-1 mutant worms, indicating that these compounds exerted their actions through these genes in extending the lifespan of C. elegans. These compounds induced DAF-16::GFP nuclear translocation and upregulated the expressions of daf-16, hsp-16.2, sod-3 mRNA and SOD-3::GFP. Moreover, they also elevated protein and mRNA expressions of GST-4, which is a downstream target of the SKN-1 transcription factor. Taken together, the study demonstrated the anti-aging activities of 2-BTHF and palmitic acid from H. scabra were mediated via DAF-16/FOXO insulin/IGF and SKN-1/NRF2 signaling pathways.

Automated summary

The present study investigated the anti-aging activity of purified compounds from the sea cucumber, Holothuria scabra, in a Caenorhabditis elegans model. It was found that 2-BTHF and palmitic acid could extend the lifespan of the worms and enhance their resistance to oxidative and thermal stress. The study also revealed that these compounds exerted their actions through the DAF-16/FOXO insulin/IGF and SKN-1/NRF2 signaling pathways.