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Volume 15
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Article

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

by
Prapaporn Jattujan
1,2,
Sirin Srisirirung
1,
Warisra Watcharaporn
1,
Kawita Chumphoochai
3,
Pichnaree Kraokaew
3,
Tanatcha Sanguanphun
3,
Prachayaporn Prasertsuksri
3,
Salinthip Thongdechsri
3,
Prasert Sobhon
3 and
Krai Meemon
3,4,*
1
Chulabhorn International College of Medicine, Rangsit Campus, Thammasat University, Pathum Thani 12120, Thailand
2
Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
3
Department of Anatomy, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand
4
Center for Neuroscience, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2022, 15(11), 1374; https://doi.org/10.3390/ph15111374
Submission received: 20 October 2022 / Revised: 4 November 2022 / Accepted: 7 November 2022 / Published: 9 November 2022
(This article belongs to the Special Issue Discovery, Metabolism and Potential Bio-Activities of Natural Products in Traditional Medicine)
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Abstract

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.
Keywords: lifespan; oxidative stress; Holothuria scabra; Caenorhabditis elegans; DAF-16; SKN-1 lifespan; oxidative stress; Holothuria scabra; Caenorhabditis elegans; DAF-16; SKN-1

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MDPI and ACS Style

Jattujan, P.; Srisirirung, S.; Watcharaporn, W.; Chumphoochai, K.; Kraokaew, P.; Sanguanphun, T.; Prasertsuksri, P.; Thongdechsri, S.; Sobhon, P.; Meemon, K. 2-Butoxytetrahydrofuran and Palmitic Acid from Holothuria scabra Enhance C. elegans Lifespan and Healthspan via DAF-16/FOXO and SKN-1/NRF2 Signaling Pathways. Pharmaceuticals 2022, 15, 1374. https://doi.org/10.3390/ph15111374

AMA Style

Jattujan P, Srisirirung S, Watcharaporn W, Chumphoochai K, Kraokaew P, Sanguanphun T, Prasertsuksri P, Thongdechsri S, Sobhon P, Meemon K. 2-Butoxytetrahydrofuran and Palmitic Acid from Holothuria scabra Enhance C. elegans Lifespan and Healthspan via DAF-16/FOXO and SKN-1/NRF2 Signaling Pathways. Pharmaceuticals. 2022; 15(11):1374. https://doi.org/10.3390/ph15111374

Chicago/Turabian Style

Jattujan, Prapaporn, Sirin Srisirirung, Warisra Watcharaporn, Kawita Chumphoochai, Pichnaree Kraokaew, Tanatcha Sanguanphun, Prachayaporn Prasertsuksri, Salinthip Thongdechsri, Prasert Sobhon, and Krai Meemon. 2022. "2-Butoxytetrahydrofuran and Palmitic Acid from Holothuria scabra Enhance C. elegans Lifespan and Healthspan via DAF-16/FOXO and SKN-1/NRF2 Signaling Pathways" Pharmaceuticals 15, no. 11: 1374. https://doi.org/10.3390/ph15111374

APA Style

Jattujan, P., Srisirirung, S., Watcharaporn, W., Chumphoochai, K., Kraokaew, P., Sanguanphun, T., Prasertsuksri, P., Thongdechsri, S., Sobhon, P., & Meemon, K. (2022). 2-Butoxytetrahydrofuran and Palmitic Acid from Holothuria scabra Enhance C. elegans Lifespan and Healthspan via DAF-16/FOXO and SKN-1/NRF2 Signaling Pathways. Pharmaceuticals, 15(11), 1374. https://doi.org/10.3390/ph15111374

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