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

• Main Authors: Prapaporn Jattujan (Author), Sirin Srisirirung (Author), Warisra Watcharaporn (Author), Kawita Chumphoochai (Author), Pichnaree Kraokaew (Author), Tanatcha Sanguanphun (Author), Prachayaporn Prasertsuksri (Author), Salinthip Thongdechsri (Author), Prasert Sobhon (Author), Krai Meemon (Author)
• Format: Book
• Published: MDPI AG, 2022-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Extracts from a sea cucumber, <i>Holothuria scabra</i>, have been shown to exhibit various pharmacological properties including anti-oxidation, anti-aging, anti-cancer, and anti-neurodegeneration. Furthermore, certain purified compounds from <i>H. scabra</i> displayed neuroprotective effects against Parkinson's and Alzheimer's diseases. Therefore, in the present study, we further examined the anti-aging activity of purified <i>H. scabra</i> compounds in a <i>Caenorhabditis elegans</i> model. Five compounds were isolated from ethyl acetate and butanol fractions of the body wall of <i>H. scabra</i> 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 <i>C. elegans</i>. 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 <i>daf-16</i>, <i>age-1</i>, <i>sir-2.1</i>, <i>jnk-1</i>, and <i>skn-1</i> mutant worms, indicating that these compounds exerted their actions through these genes in extending the lifespan of <i>C. elegans</i>. These compounds induced DAF-16::GFP nuclear translocation and upregulated the expressions of <i>daf-16</i>, <i>hsp-16.2</i>, <i>sod-3</i> 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 <i>H. scabra</i> were mediated via DAF-16/FOXO insulin/IGF and SKN-1/NRF2 signaling pathways.

Item Description

10.3390/ph15111374
1424-8247