<iframe src="//www.googletagmanager.com/ns.html?id=GTM-5TSRKG" height="0" width="0" style="display: none; visibility: hidden">
Research Article
No access
Published Online: 17 January 2013

Quinic Acid Could Be a Potential Rejuvenating Natural Compound by Improving Survival of Caenorhabditis elegans under Deleterious Conditions

Publication: Rejuvenation Research
Volume 15, Issue Number 6

Abstract

Quinic acid (QA) is an active ingredient of Cat's Claw (Uncaria tomentosa), which is found to be active in enhancing DNA repair and immunity in model systems and able to generate neuroprotective effects in neurons. However, QA's role in improving survival is not well studied. Here we report that QA can provide protection in Caenorhabidits elegans and improve worm survival under stress. Under heat stress and oxidative stress, QA-treated wild-type C. elegans N2 (N2) survived 17.8% and 29.7% longer, respectively, than the control worms. Our data suggest that under heat stress, QA can upregulate the expression of the small heat shock protein hsp-16.2 gene, which could help the worms survive a longer time. We also found that QA extended the C. elegans mutant VC475 [hsp-16.2 (gk249)] life span by 15.7% under normal culture conditions. However, under normal culture conditions, QA did not affect hsp-16.2 expression, but upregulated the expression of daf-16 and sod-3 in a DAF-16–dependent manner, and downregulated the level of reactive oxygen species (ROS), suggesting that under normal conditions QA acts in different pathways. As a natural product, QA demonstrates great potential as a rejuvenating compound.

Get full access to this article

View all available purchase options and get full access to this article.

References

1.
Howitz KTBitterman KJCohen HYLamming DWLavu SWood JGZipkin REChung PKisielewski AZhang LL et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespanNature2003425191-196. 1. Howitz, KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003;425:191–196.
2.
Wood JGRogina BLavu SHowitz KHelfand SLTatar MSinclair D. Sirtuin activators mimic caloric restriction and delay ageing in metazoansNature2004430686-689. 2. Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 2004;430:686–689.
3.
Bass TMWeinkove DHouthoofd KGems DPartridge L. Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegansMech Ageing Dev2007128546-552. 3. Bass TM, Weinkove D, Houthoofd K, Gems D, Partridge L. Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans. Mech Ageing Dev 2007;128:546–552.
4.
Valenzano DRTerzibasi EGenade TCattaneo ADomenici LCellerino A. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrateCurr Biol200616296-300. 4. Valenzano DR, Terzibasi E, Genade T, Cattaneo A, Domenici L, Cellerino A. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol 2006;16:296–300.
5.
Baur JAPearson KJPrice NLJamieson HALerin CKalra APrabhu VVAllard JSLopez-Lluch GLewis K et al. Resveratrol improves health and survival of mice on a high-calorie dietNature2006444337-342. 5. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006;444:337–342.
6.
Sheng YPero RWAmiri ABryngelsson C. Induction of apoptosis and inhibition of proliferation in human tumor cells treated with extracts of Uncaria tomentosaAnticancer Res1998183363-3368. 6. Sheng Y, Pero RW, Amiri A, Bryngelsson C. Induction of apoptosis and inhibition of proliferation in human tumor cells treated with extracts of Uncaria tomentosa. Anticancer Res 1998;18:3363–3368.
7.
Sheng YBryngelsson CPero RW. Enhanced DNA repair, immune function and reduced toxicity of C-MED-100, a novel aqueous extract from Uncaria tomentosaJ Ethnopharmacol200069115-126. 7. Sheng Y, Bryngelsson C, Pero RW. Enhanced DNA repair, immune function and reduced toxicity of C-MED-100, a novel aqueous extract from Uncaria tomentosa. J Ethnopharmacol 2000;69:115–126.
8.
Sheng YLi LHolmgren KPero RW. DNA repair enhancement of aqueous extracts of Uncaria tomentosa in a human volunteer studyPhytomedicine20018275-282. 8. Sheng Y, Li L, Holmgren K, Pero RW. DNA repair enhancement of aqueous extracts of Uncaria tomentosa in a human volunteer study. Phytomedicine 2001;8:275–282.
9.
Pero RWAmiri ASheng YWelther MRich M. Formulation and in vitro/in vivo evaluation of combining DNA repair and immune enhancing nutritional supplementsPhytomedicine200512255-263. 9. Pero RW, Amiri A, Sheng Y, Welther M, Rich M. Formulation and in vitro/in vivo evaluation of combining DNA repair and immune enhancing nutritional supplements. Phytomedicine 2005;12:255–263.
10.
Mammone TAkesson CGan DGiampapa VPero RW. A water soluble extract from Uncaria tomentosa (Cat's Claw) is a potent enhancer of DNA repair in primary organ cultures of human skinPhytother Res200620178-183. 10. Mammone T, Akesson C, Gan D, Giampapa V, Pero RW. A water soluble extract from Uncaria tomentosa (Cat's Claw) is a potent enhancer of DNA repair in primary organ cultures of human skin. Phytother Res 2006;20:178–183.
11.
Sheng YAkesson CHolmgren KBryngelsson CGiamapa VPero RW. An active ingredient of Cat's Claw water extracts identification and efficacy of quinic acidJ Ethnopharmacol200596577-584. 11. Sheng Y, Akesson C, Holmgren K, Bryngelsson C, Giamapa V, Pero RW. An active ingredient of Cat's Claw water extracts identification and efficacy of quinic acid. J Ethnopharmacol 2005;96:577–584.
12.
Brenner S. The genetics of Caenorhabditis elegansGenetics19747771-94. 12. Brenner S. The genetics of Caenorhabditis elegans. Genetics 1974;77:71–94.
13.
Gandhi SSantelli JMitchell DHStiles JWSanadi DR. A simple method for maintaining large, aging populations of Caenorhabditis elegansMech Ageing Dev198012137-150. 13. Gandhi S, Santelli J, Mitchell DH, Stiles JW, Sanadi DR. A simple method for maintaining large, aging populations of Caenorhabditis elegans. Mech Ageing Dev 1980;12:137–150.
14.
Aitlhadj LSturzenbaum SR. The use of FUdR can cause prolonged longevity in mutant nematodesMech Ageing Dev2010131364-365. 14. Aitlhadj L, Sturzenbaum SR. The use of FUdR can cause prolonged longevity in mutant nematodes. Mech Ageing Dev 2010;131:364–365.
15.
Hansen MHsu ALDillin AKenyon C. New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screenPLoS Genet20051119-128. 15. Hansen M, Hsu AL, Dillin A, Kenyon C. New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen. PLoS Genet 2005;1:119–128.
16.
Lithgow GJWhite TMMelov SJohnson TE. Thermotolerance, extended life-span conferred by single-gene mutations, induced by thermal stressProc Natl Acad Sci USA1995927540-7544. 16. Lithgow GJ, White TM, Melov S, Johnson TE.Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc Natl Acad Sci USA 1995;92:7540–7544.
17.
Rea SLWu DCypser JRVaupel JWJohnson TE. A stress-sensitive reporter predicts longevity in isogenic populations of Caenorhabditis elegansNat Genet200537894-898. 17. Rea SL, Wu D, Cypser JR, Vaupel JW, Johnson TE. A stress-sensitive reporter predicts longevity in isogenic populations of Caenorhabditis elegans. Nat Genet 2005;37:894–898.
18.
Strayer AWu ZChristen YLink CDLuo Y. Expression of the small heat-shock protein Hsp16-2 in Caenorhabditis elegans is suppressed by Ginkgo biloba extract EGb 761FASEB J2003172305-2307. 18. Strayer A, Wu Z, Christen Y, Link CD, Luo Y. Expression of the small heat-shock protein Hsp16-2 in Caenorhabditis elegans is suppressed by Ginkgo biloba extract EGb 761. FASEB J 2003;17:2305–2307.
19.
Jian L. Increased carbon disulfide-stimulated chemiluminescence in the pyrogallol-luminol systemLuminescence200116281-283. 19. Jian L. Increased carbon disulfide-stimulated chemiluminescence in the pyrogallol-luminol system. Luminescence 2001;16:281–283.
20.
Arkblad ELTuck SPestov NBDmitriev RIKostina MBStenvall JTranberg MRydstrom J. A Caenorhabditis elegans mutant lacking functional nicotinamide nucleotide transhydrogenase displays increased sensitivity to oxidative stressFree Radical Biol Med2005381518-1525. 20. Arkblad EL, Tuck S, Pestov NB, Dmitriev RI, Kostina MB, Stenvall J, Tranberg M, Rydstrom J. A Caenorhabditis elegans mutant lacking functional nicotinamide nucleotide transhydrogenase displays increased sensitivity to oxidative stress. Free Radical Biol Med 2005;38:1518–1525.
21.
Bass DAParce JWDechatelet LRSzejda PSeeds MCThomas M. Flow cytometric studies of oxidative product formation by neutrophils: A graded response to membrane stimulationJ Immunol19831301910-1917. 21. Bass DA, Parce JW, Dechatelet LR, Szejda P, Seeds MC, Thomas M. Flow cytometric studies of oxidative product formation by neutrophils: A graded response to membrane stimulation. J Immunol 1983;130:1910–1917.
22.
Gutierrez-Zepeda ASantell RWu ZBrown MWu YKhan ILink CDZhao BLuo Y. Soy isoflavone glycitein protects against beta amyloid-induced toxicity and oxidative stress in transgenic Caenorhabditis elegansBMC Neurosci2005654. 22. Gutierrez-Zepeda A, Santell R, Wu Z, Brown M, Wu Y, Khan I, Link CD, Zhao B, Luo Y. Soy isoflavone glycitein protects against beta amyloid-induced toxicity and oxidative stress in transgenic Caenorhabditis elegans. BMC Neurosci 2005;6:54.
23.
Kraynov VSChamberlain CBokoch GMSchwartz MASlabaugh SHahn KM. Localized Rac activation dynamics visualized in living cellsScience2000290333-337. 23. Kraynov VS, Chamberlain C, Bokoch GM, Schwartz MA, Slabaugh S, Hahn KM. Localized Rac activation dynamics visualized in living cells. Science 2000;290:333–337.
24.
Livak KJSchmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) MethodMethods200125402-408. 24. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001;25:402–408.
25.
Seve MChimienti FDevergnas SAouffen MDouki TChantegrel JCadet JFavier A. Resveratrol enhances UVA-induced DNA damage in HaCaT human keratinocytesMed Chem20051629-633. 25. Seve M, Chimienti F, Devergnas S, Aouffen M, Douki T, Chantegrel J, Cadet J, Favier A. Resveratrol enhances UVA-induced DNA damage in HaCaT human keratinocytes. Med Chem 2005;1:629–633.
26.
Hsu ALMurphy CTKenyon C. Regulation of aging and age-related disease by DAF-16 and heat-shock factorScience20033001142-1145. 26. Hsu AL, Murphy CT, Kenyon C. Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 2003;300:1142–1145.
27.
Tissenbaum HAGuarente L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegansNature2001410227-230. 27. Tissenbaum HA, Guarente L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 2001;410:227–230.
28.
Lin KHsin HLibina NKenyon C. Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signalingNat Genet200128139-145. 28. Lin K, Hsin H, Libina N, Kenyon C. Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat Genet 2001;28:139–145.
29.
Lin KDorman JBRodan AKenyon C. daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegansScience19972781319-1322. 29. Lin K, Dorman JB, Rodan A, Kenyon C. daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 1997;278:1319–1322.
30.
Gottlieb SRuvkun G. daf-2, daf-16 and daf-23: Genetically interacting genes controlling Dauer formation in Caenorhabditis elegansGenetics1994137107-120. 30. Gottlieb S, Ruvkun G. daf-2, daf-16 and daf-23: Genetically interacting genes controlling Dauer formation in Caenorhabditis elegans. Genetics 1994;137:107–120.
31.
Harman D. Aging: A theory based on free radical and radiation chemistryJ Gerontol195611298-300. 31. Harman D. Aging: A theory based on free radical and radiation chemistry. J Gerontol 1956;11:298–300.
32.
Jones DP. Redefining oxidative stressAntiox Redox Signal200681865-1879. 32. Jones DP: Redefining oxidative stress. Antiox Redox Signal 2006;8:1865–1879.
33.
Rahman IBiswas SKJimenez LATorres MForman HJ. Glutathione, stress responses, and redox signaling in lung inflammationAntiox Redox Signal2005742-59. 33. Rahman I, Biswas SK, Jimenez LA, Torres M, Forman HJ. Glutathione, stress responses, and redox signaling in lung inflammation. Antiox Redox Signal 2005;7:42–59.
34.
Burmeister CLuersen KHeinick AHussein ADomagalski MWalter RDLiebau E. Oxidative stress in Caenorhabditis elegans: Protective effects of the Omega class glutathione transferase (GSTO-1)FASEB J200722343-354. 34. Burmeister C, Luersen K, Heinick A, Hussein A, Domagalski M, Walter RD, Liebau E. Oxidative stress in Caenorhabditis elegans: Protective effects of the Omega class glutathione transferase (GSTO-1). FASEB J 2007;22:343–354.
35.
Kampkotter AGombitang Nkwonkam CZurawski RFTimpel CChovolou YWatjen WKahl R. Effects of the flavonoids kaempferol and fisetin on thermotolerance, oxidative stress and FoxO transcription factor DAF-16 in the model organism Caenorhabditis elegansArch Toxicol200781849-858. 35. Kampkotter A, Gombitang Nkwonkam C, Zurawski RF, Timpel C, Chovolou Y, Watjen W, Kahl R. Effects of the flavonoids kaempferol and fisetin on thermotolerance, oxidative stress and FoxO transcription factor DAF-16 in the model organism Caenorhabditis elegans. Arch Toxicol 2007;81:849–858.
36.
Dengg Mvan Meel JC. Caenorhabditis elegans as model system for rapid toxicity assessment of pharmaceutical compoundsJ Pharmacol Toxicol Methods200450209-214. 36. Dengg M, van Meel JC. Caenorhabditis elegans as model system for rapid toxicity assessment of pharmaceutical compounds. J Pharmacol Toxicol Methods 2004;50:209–214.
37.
Link CDCypser JRJohnson CJJohnson TE. Direct observation of stress response in Caenorhabditis elegans using a reporter transgeneCell Stress Chaperon19994235-242. 37. Link CD, Cypser JR, Johnson CJ, Johnson TE. Direct observation of stress response in Caenorhabditis elegans using a reporter transgene. Cell Stress Chaperon 1999;4:235–242.

Information & Authors

Information

Published In

cover image Rejuvenation Research
Rejuvenation Research
Volume 15Issue Number 6December 2012
Pages: 573 - 583
PubMed: 22950425

History

Published online: 17 January 2013
Published in print: December 2012
Published ahead of print: 24 September 2012
Published ahead of production: 5 September 2012
Accepted: 11 June 2012
Received: 11 April 2012

Permissions

Request permissions for this article.

Topics

    Authors

    Affiliations

    Longze Zhang
    State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
    Graduate School of the Chinese Academy of Sciences, Beijing 100029, P.R. China.
    Junjing Zhang
    State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
    Baolu Zhao
    State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
    Graduate School of the Chinese Academy of Sciences, Beijing 100029, P.R. China.
    Division of Nitric Oxide and Inflammatory Medicine, E-Institutes of Shanghai Universities, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
    Xi Zhao-Wilson
    BioMarker Pharmaceuticals, Inc. 5941 Optical Court, San Jose, California.

    Notes

    Address correspondence to:Xi Zhao-WilsonBioMarker Pharmaceuticals, Inc.5941 Optical CourtSan Jose, CA 95138E-mail: [email protected]
    Baolu ZhaoInstitute of BiophysicsAcademia SinicaNo. 15, Datun Road, Chaoyang DistrictBeijing 100101P.R. China
    E-mail: [email protected]

    Author Disclosure Statement

    No competing financial interests exist.

    Metrics & Citations

    Metrics

    Citations

    Export citation

    Select the format you want to export the citations of this publication.

    View Options

    Get Access

    Access content

    To read the fulltext, please use one of the options below to sign in or purchase access.

    Society Access

    If you are a member of a society that has access to this content please log in via your society website and then return to this publication.

    Restore your content access

    Enter your email address to restore your content access:

    Note: This functionality works only for purchases done as a guest. If you already have an account, log in to access the content to which you are entitled.

    View options

    PDF/EPUB

    View PDF/ePub

    Full Text

    View Full Text

    Media

    Figures

    Other

    Tables

    Share

    Share

    Copy the content Link

    Share on social media

    Back to Top