2-Butoxytetrahydrofuran and Palmitic Acid from Holothuria scabra Enhance C. elegans Lifespan and Healthspan via DAF-16/FOXO and SKN-1/NRF2 Signaling Pathways
Abstract
:1. Introduction
2. Results
2.1. Effects of Purified of H. scabra Extracts on the Lifespan of C. elegans
2.2. Effects of Purified H. scabra Compounds on C. elegans’ Resistance to Thermal Stress
2.3. Effects of Purified H. scabra Compounds on C. elegans’ Resistance to Oxidative Stress
2.4. Effects of Purified H. scabra Compounds on the Pathways That Control Lifespans of C. elegans
2.5. DAF-16 Translocation
2.6. SOD-3 Expression
2.7. HSP-16.2 Expression
2.8. GST-4 Expression
2.9. Expression of mRNA Transcripts
3. Discussion
4. Materials and Methods
4.1. H. scabra Extraction and Purification
4.2. C. elegans Strains and Growth Conditions
4.3. Lifespan Assays
4.4. Stress Resistance Assays
4.5. Lifespan Assays of Mutant Worms
4.6. DAF-16 Translocation and SOD-3, HSP-16.2, and GST-4 Expression in Transgenic Strains of C. elegans
4.7. Gene Expression Analysis by Quantitative RT-PCR
4.8. Data Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Compounds | Lifespan (Mean ± SD) | (Number of Worms, Censored) | % Increase Lifespan | p Value (Log-Rank Test) |
---|---|---|---|---|
1% DMSO | 12.28 ± 1.76 | (145, 8) | - | - |
1 μg/mL DEHP | 12.18 ± 1.97 | (137, 2) | −0.81 | 0.9737 |
5 μg/mL DEHP | 12.36 ± 2.10 | (145, 4) | 0.65 | 0.2603 |
10 μg/mL DEHP | 12.29 ± 2.49 | (129, 2) | 0.08 | 0.2695 |
1% DMSO | 12.04 ± 1.91 | (126, 2) | - | - |
1 μg/mL 2-BTHF | 12.35 ± 1.86 | (127, 9) | 2.57 | 0.1694 |
5 μg/mL 2-BTHF | 12.72 ± 1.90 | (151, 2) | 5.65 | 0.0012 ** |
10 μg/mL 2-BTHF | 12.37 ± 2.36 | (142, 3) | 2.74 | 0.0192 * |
1% DMSO | 11.10 ± 1.70 | (118, 2) | - | - |
1 μg/mL holothuria A | 11.13 ± 1.88 | (121, 2) | 0.27 | 0.5654 |
5 μg/mL holothuria A | 11.45 ± 1.79 | (118, 1) | 3.15 | 0.0895 |
10 μg/mL holothuria A | 11.44 ± 1.77 | (123, 3) | 3.06 | 0.0703 |
1% DMSO | 12.12 ± 2.14 | (123, 0) | - | - |
1 μg/mL holothuria B | 12.07 ± 1.91 | (134, 0) | −0.41 | 0.5685 |
5 μg/mL holothuria B | 12.17 ± 2.00 | (134, 2) | 0.41 | 0.8980 |
10 μg/mL holothuria B | 12.30 ± 1.85 | (112, 1) | 1.49 | 0.8498 |
1% DMSO | 11.45 ± 1.87 | (132, 4) | - | - |
1 μg/mL palmitic acid | 11.99 ± 1.86 | (148, 2) | 4.72 | 0.0207 * |
5 μg/mL palmitic acid | 11.46 ± 1.92 | (127, 0) | 0.09 | 0.8550 |
10 μg/mL palmitic acid | 11.48 ± 1.96 | (145, 0) | 0.26 | 0.8037 |
Strains of Worm | Compounds | Lifespan (Mean ± SD) | (Number of Worms, Censored) | % Increase Lifespan | p Value (Log-Rank Test) |
---|---|---|---|---|---|
N2 | 1% DMSO | 13.79 ± 2.40 | (118, 0) | - | - |
5 μg/mL 2-BTHF | 15.20 ± 2.34 | (190, 0) | 10.22 | <0.0001 **** | |
10 μg/mL 2-BTHF | 14.50 ± 2.60 | (126, 0) | 5.15 | 0.0174 * | |
1 μg/mL palmitic acid | 14.49 ± 2.11 | (163, 0) | 5.08 | 0.0422 * | |
CF1038 (daf-16(mu86)) | 1% DMSO | 11.42 ± 1.30 | (90, 0) | - | - |
5 μg/mL 2-BTHF | 11.33 ± 1.47 | (86, 0) | −0.79 | 0.9129 | |
10 μg/mL 2-BTHF | 11.16 ± 1.49 | (86, 0) | −2.28 | 0.3820 | |
1 μg/mL palmitic acid | 11.73 ± 1.48 | (85, 0) | 2.71 | 0.1169 | |
VC199 (sir-2.1(ok434)) | 1% DMSO | 10.51 ± 2.86 | (215, 0) | - | - |
5 μg/mL 2-BTHF | 11.08 ± 3.26 | (203, 0) | 5.42 | 0.0416 * | |
10 μg/mL 2-BTHF | 10.13 ± 2.36 | (178, 0) | −3.62 | 0.0799 | |
1 μg/mL palmitic acid | 10.81 ± 2.86 | (266, 1) | 2.85 | 0.2841 | |
VC8 (jnk-1(gk7)) | 1% DMSO | 15.51 ± 2.46 | (176, 2) | - | - |
5 μg/mL 2-BTHF | 15.32 ± 2.44 | (92, 0) | −1.23 | 0.5789 | |
10 μg/mL 2-BTHF | 15.91 ± 2.43 | (139, 1) | 2.58 | 0.1965 | |
1 μg/mL palmitic acid | 15.52 ± 2.49 | (133, 0) | 0.06 | 0.8594 | |
TJ1052 (age-1(hx546)) | 1% DMSO | 22.16 ± 3.60 | (100, 0) | - | - |
5 μg/mL 2-BTHF | 20.87 ± 3.06 | (111, 0) | −5.82 | 0.0002 *** | |
10 μg/mL 2-BTHF | 21.96 ± 2.57 | (119, 0) | −0.90 | 0.0136 * | |
1 μg/mL palmitic acid | 22.29 ± 4.39 | (130, 0) | 0.59 | 0.6533 | |
EU1 (skn-1(zu67) IV) | 1% DMSO | 12.28 ± 1.76 | (145, 0) | - | - |
5 μg/mL 2-BTHF | 12.18 ± 1.97 | (137, 0) | −0.81 | 0.9737 | |
10 μg/mL 2-BTHF | 12.36 ± 2.10 | (145, 0) | 0.65 | 0.2603 | |
1 μg/mL palmitic acid | 12.29 ± 2.49 | (129, 0) | 0.08 | 0.2695 |
Genes | Forward Primers | Reverse Primers |
---|---|---|
daf-16 | 5′-CCAGACGGAAGGCTTAAACT-3′ | 5′-ATTCGCATGAAACGAGAATG-3′ |
hsp-16.2 | 5′-GTCACTTTACCACTATTTCCGT-3′ | 5′-CAATCTCAGAAGACTCAGATGG-3′ |
sod-3 | 5′-CCAACCAGCGCTGAAATTCAATGG-3′ | 5′-GGAACCGAAGTCGCGCTTAATAGT-3′ |
gst-4 | 5′- CCCATTTTACAAGTCGATGG-3′ | 5′-CTTCCTCTGCAGTTTTTCCA-3′ |
act-1 | 5′-ATCGTCACCACCAGCTTTCT-3′ | 5′-CACACCCGCAAATGAGTGAA-3′ |
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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
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 StyleJattujan, 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