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http://dx.doi.org/10.4062/biomolther.2017.215

Longevity and Stress Resistant Property of 6-Gingerol from Zingiber officinale Roscoe in Caenorhabditis elegans  

Lee, Eun Byeol (College of Pharmacy, Woosuk University)
Kim, Jun Hyeong (College of Pharmacy, Woosuk University)
An, Chang Wan (College of Pharmacy, Woosuk University)
Kim, Yeong Jee (College of Pharmacy, Woosuk University)
Noh, Yun Jeong (College of Pharmacy, Woosuk University)
Kim, Su Jin (College of Pharmacy, Woosuk University)
Kim, Ju-Eun (College of Pharmacy, Woosuk University)
Shrestha, Abinash Chandra (College of Pharmacy, Woosuk University)
Ham, Ha-Neul (College of Pharmacy, Woosuk University)
Leem, Jae-Yoon (College of Pharmacy, Woosuk University)
Jo, Hyung-Kwon (Hanpoong Pharm. Co., LTD)
Kim, Dae-Sung (Hanpoong Pharm. Co., LTD)
Moon, Kwang Hyun (Sunchang Research Institute of Health and Longevity)
Lee, Jeong Ho (Sunchang Research Institute of Health and Longevity)
Jeong, Kyung Ok (Sunchang Research Institute of Health and Longevity)
Kim, Dae Keun (College of Pharmacy, Woosuk University)
Publication Information
Biomolecules & Therapeutics / v.26, no.6, 2018 , pp. 568-575 More about this Journal
Abstract
In order to discover lifespan-extending compounds made from natural resources, activity-guided fractionation of Zingiber officinale Roscoe (Zingiberaceae) ethanol extract was performed using the Caenorhabditis elegans (C. elegans) model system. The compound 6-gingerol was isolated from the most active ethyl acetate soluble fraction, and showed potent longevity-promoting activity. It also elevated the survival rate of worms against stressful environment including thermal, osmotic, and oxidative conditions. Additionally, 6-gingerol elevated the antioxidant enzyme activities of C. elegans, and showed a dose-depend reduction of intracellular reactive oxygen species (ROS) accumulation in worms. Further studies demonstrated that the increased stress tolerance of 6-gingerol-mediated worms could result from the promotion of stress resistance proteins such as heat shock protein (HSP-16.2) and superoxide dismutase (SOD-3). The lipofuscin levels in 6-gingerol treated intestinal worms were decreased in comparison to the control group. No significant 6-gingerol-related changes, including growth, food intake, reproduction, and movement were noted. These results suggest that 6-gingerol exerted longevity-promoting activities independently of these factors and could extend the human lifespan.
Keywords
Zingiber officinale Roscoe; 6-Gingerol; Caenorhabditis elegans; Longevity; Stress tolerance;
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1 Aebi, H. (1984) Catalase in vitro. Methods Enzymol. 105, 121-126.
2 Al-Nahain, A., Jahan, R. and Rahmatullah, M. (2014) Zingiber officinale: a potential plant against rheumatoid arthritis. Arthritis 2014, 159089.
3 Baranov, V. S. and Baranova, E. V. (2017) Aging and ambiguous ROS. System genetics analysis. Curr. Aging Sci. 10, 6-11.   DOI
4 Beckman, K. B. and Ames, B. N. (1998) The free radical theory of aging matures. Physiol. Rev. 78, 547-581.   DOI
5 Berlett, B. S. and Stadtman, E. R. (1997) Protein oxidation in aging, disease, and oxidative stress. J. Bio. Chem. 272, 20313-20316.   DOI
6 Brenner, S. (1974) The genetics of Caenorhabditis elegans. Genetics 77, 71-94.
7 Kaletsky, R. and Murphy, C. T. (2010) The role of insulin/IGF-like signaling in C. elegans longevity and aging. Dis. Model Mech. 3, 415-419.   DOI
8 Kenyon, C. J. (2010) The genetics of ageing. Nature 464, 504-512.   DOI
9 Kim, E. C., Min, J. K., Kim, T. Y., Lee, S. J., Yang, H. O., Han, S., Kim, Y. M. and Kwon, Y. G. (2005) [6]-Gingerol, a pungent ingredient of ginger, inhibits angiogenesis in vitro and in vivo. Biochem. Biophys Res. Commun. 335, 300-308.   DOI
10 Lee, E. Y., Shim, Y. H., Chitwood, D. J., Hwang, S. B., Lee, J. and Paik, Y. K. (2005) Cholesterol-producing transgenic Caenorhabditis elegans lives longer due to newly acquired enhanced stress resistance. Biochem. Biophys. Res. Commun. 328, 929-936.   DOI
11 Lithgow, G. J., White, T. M., Melov, S. and Johnson, T. E. (1995) Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc. Natl. Acad. Sci. U.S.A. 92, 7540-7544.   DOI
12 Mekheimer, R. A., Sayed, A. A. and Ahmed, E. A. (2012) Novel 1,2,4-triazolo[1,5-a]pyridines and their fused ring systems attenuate oxidative stress and prolong lifespan of Caenorhabiditis elegans. J. Med. Chem. 55, 4169-4177.   DOI
13 Morck, C. and Pilon, M. (2006) C. elegans feeding defective mutants have shorter body lengths and increased autophagy. BMC Dev. Biol. 6, 39.   DOI
14 Na, M. K. and Bae, K. H. (2011) Natural compounds with antioxidant activity: recent findings from studies on medicinal plants. Nat. Prod. Sci. 17, 65-79.
15 Park, G., Oh, D. S., Lee, M. G., Lee, C. E. and Kim, Y. U. (2016) 6-Shogaol, an active compound of ginger, alleviates allergic dermatitis-like skin lesions via cytokine inhibition by activating the Nrf2 pathway. Toxicol. Appl. Pharmacol. 310, 51-59.   DOI
16 Partridge, L., Gems, D. and Withers, D. J. (2005) Sex and death: what is the connection? Cell 120, 461-472.   DOI
17 Pelicano, H., Carney, D. and Huang, P. (2004) ROS stress in cancer cells and therapeutic implications. Drug Resist. Updat. 7, 97-110.   DOI
18 Rastogi, N., Gara, R. K., Trivedi, R., Singh, A., Dixit, P., Maurya, R., Duggal, S., Bhatt, M. L., Singh, S. and Mishra, D. P. (2014) (6)-Gingerol induced myeloid leukemia cell death is initiated by reactive oxygen species and activation of miR-27b expression. Free Radic. Biol. Med. 68, 288-301.   DOI
19 Pinazo-Duran, M. D., Gallego-Pinazo, R., Garcia-Medina, J. J., Zanon-Moreno, V., Nucci, C., Dolz-Marco, R., Martinez-Castillo, S., Galbis-Estrada, C., Marco-Ramirez, C., Lopez-Galvez, M. I., Galarreta, D. J. and Diaz-Llopis, M. (2014) Oxidative stress and its downstream signaling in aging eyes. Clin. Interv. Aging 9, 637-652.
20 Pujol, N., Zugasti, O., Wong, D., Couillault, C., Kurz, C. L., Schulenburg, H. and Ewbank, J. J. (2008) Anti-fungal innate immunity in C. elegans is enhanced by evolutionary diversification of antimicrobial peptides. PLoS Pathog. 4, e1000105.   DOI
21 Sayed, A. A. (2011) Ferulsinaic acid attenuation of advanced glycation end products extends the lifespan of Caenorhabditis elegans. J. Pharm. Pharmacol. 63, 423-428.   DOI
22 Seo, C.-S., Kim, J.-H., Shin, H.-K. and Kim, B.-S. (2017) Content of 6-gingerol in Zingiberis Rhizoma by roasting. Kor. J. Pharmacogn. 48, 226-231.
23 Seo, H. W., Cheon, S. M., Lee, M. H., Kim, H. J., Jeon, H. and Cha, D. S. (2015) Catalpol modulates lifespan via DAF-16/FOXO and SKN-1/Nrf2 activation in Caenorhabditis elegans. Evid. Based. Complement. Alternat. Med. 2015, 524878.
24 Shoji, N., Iwasa, A., Takemoto, T., Ishida, Y. and Ohizumi, Y. (1982) Cardiotonic principles of ginger (Zingiber officinale Roscoe). J. Pharm. Sci. 71, 1174-1175.   DOI
25 Singh,. R., Devi, S. and Gollen, R. (2015) Role of free radical in atherosclerosis, diabetes and dyslipidaemia: larger-than-life. Diabetes Metab. Res. Rev. 31, 113-126.   DOI
26 Weir, T. L., Park, S. W. and Vivanco, J. M. (2004) Biochemical and physiological mechanisms mediated by allelochemicals. Curr. Opin. Plant Biol. 7, 472-479.   DOI
27 Surco-Laos, F., Duenas, M., Gonzalez-Manzano, S., Cabello, J., Santos-Buelga, C., Gonzalez-Paramas, A. M. (2012) Influence of catechins and their methylated metabolites on lifespan and resistance to oxidative and thermal stress of Caenorhabditis elegans and epicatechin uptake. Food Res. Int. 46, 514-521.   DOI
28 Swindell, W. R. (2009) Heat shock proteins in long-lived worms and mice with insulin/insulin-like signaling mutations. Aging (Albany N.Y.) 1, 573-577.
29 Terman, A. and Brunk, U. T. (2004) Lipofuscin. Int. J. Biochem. Cell Biol. 36, 1400-1404.   DOI
30 Wang, Q., Huang, Y., Qin, C., Liang, M., Mao, X., Li, S., Zou, Y., Jia, W., Li, H., Ma, C. W. and Huang, Z. (2016) Bioactive peptides from Angelica sinensis protein hydrolyzate delay senescence in Caenorhabditis elegans through antioxidant activities. Oxid. Med. Cell. Longev. 2016, 8956981.
31 Weng, C. J., Wu, C. F., Huang, H. W., Ho, C. T. and Yen, G. C. (2010) Anti-invasion effects of 6-shogaol and 6-gingerol, two active components in ginger, on human hepatocarcinoma cells. Mol. Nutr. Food Res. 54, 1618-1627.   DOI
32 Willis, R. J. (2000) Juglans spp., juglone and allelopathy. Allelopathy J. 7, 1-55.
33 Wu, Z., Smith, J. V., Paramasivam, V., Butko, P., Khan, I., Cypser, J. R. and Luo, Y. (2002) Ginkgo biloba extract EGb 761 increases stress resistance and extends life span of Caenorhabditis elegans. Cell. Mol. Biol. (Noisy-le-grand) 48, 725-731.
34 Zhao, T., Zhang, Q., Qi, H., Liu, X. and Li, Z. (2008) Extension of life span and improvement of vitality of Drosophila melanogaster by long-term supplementation with different molecular weight polysaccharides from Porphyra haitanensis. Pharmacol. Res. 57, 67-72.   DOI
35 Zick, S. M., Djuric, Z., Ruffin, M. T., Litzinger, A. J., Normolle, D. P., Feng, M. R. and Brenner, D. E. (2008) Pharmacokinetics of 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol and conjugate metabolites in healthy human subjects. Cancer Epidemiol. Biomarkers Prev. 17, 1930-1936.   DOI