Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleNEUROPHARMACOLOGY

Curcumin Structure-Function, Bioavailability, and Efficacy in Models of Neuroinflammation and Alzheimer's Disease

Aynun N. Begum, Mychica R. Jones, Giselle P. Lim, Takashi Morihara, Peter Kim, Dennis D. Heath, Cheryl L. Rock, Mila A. Pruitt, Fusheng Yang, Beverly Hudspeth, Shuxin Hu, Kym F. Faull, Bruce Teter, Greg M. Cole and Sally A. Frautschy
Journal of Pharmacology and Experimental Therapeutics July 2008, 326 (1) 196-208; DOI: https://doi.org/10.1124/jpet.108.137455
Aynun N. Begum
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mychica R. Jones
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Giselle P. Lim
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takashi Morihara
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter Kim
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dennis D. Heath
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cheryl L. Rock
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mila A. Pruitt
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fusheng Yang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Beverly Hudspeth
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shuxin Hu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kym F. Faull
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bruce Teter
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Greg M. Cole
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sally A. Frautschy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Curcumin can reduce inflammation and neurodegeneration, but its chemical instability and metabolism raise concerns, including whether the more stable metabolite tetrahydrocurcumin (TC) may mediate efficacy. We examined the antioxidant, anti-inflammatory, or anti-amyloidogenic effects of dietary curcumin and TC, either administered chronically to aged Tg2576 APPsw mice or acutely to lipopolysaccharide (LPS)-injected wild-type mice. Despite dramatically higher drug plasma levels after TC compared with curcumin gavage, resulting brain levels of parent compounds were similar, correlating with reduction in LPS-stimulated inducible nitric-oxide synthase, nitrotyrosine, F2 isoprostanes, and carbonyls. In both the acute (LPS) and chronic inflammation (Tg2576), TC and curcumin similarly reduced interleukin-1β. Despite these similarities, only curcumin was effective in reducing amyloid plaque burden, insoluble β-amyloid peptide (Aβ), and carbonyls. TC had no impact on plaques or insoluble Aβ, but both reduced Tris-buffered saline-soluble Aβ and phospho-c-Jun NH2-terminal kinase (JNK). Curcumin but not TC prevented Aβ aggregation. The TC metabolite was detected in brain and plasma from mice chronically fed the parent compound. These data indicate that the dienone bridge present in curcumin, but not in TC, is necessary to reduce plaque deposition and protein oxidation in an Alzheimer's model. Nevertheless, TC did reduce neuroinflammation and soluble Aβ, effects that may be attributable to limiting JNK-mediated transcription. Because of its favorable safety profile and the involvement of misfolded proteins, oxidative damage, and inflammation in multiple chronic degenerative diseases, these data relating curcumin dosing to the blood and tissue levels required for efficacy should help translation efforts from multiple successful preclinical models.

Footnotes

  • This study was supported by Grant U01028583 (to S.A.F.), VA Merit Grants AG021975 (to S.A.F.) and AG016570 (Cummings Project 1; to G.M.C.). We are grateful for the original support of K. K. Siegel on curcumin in 1998 on a UCLA Pilot Center on Aging Grant.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • doi:10.1124/jpet.108.137455.

  • ABBREVIATIONS: AD, Alzheimer's disease; IL, interleukin; pJNK, phospho-JNK, c-Jun NH2-terminal kinase; JNK, c-Jun NH2-terminal kinase; iNOS, inducible nitric-oxide synthase; 8-iso-PGE2α, 8-iso-prostaglandin E2α; TC, tetrahydrocurcumin; LPS, lipopolysaccharide; Aβ, β-amyloid peptide; gav, gavage; PBS, phosphate-buffered saline; PMSF, phenylmethylsulfonyl fluoride; HFIP, 1,1,1,3,3,3-hexafluoro-2-propanol; LDH, lactate dehydrogenase; DMEM, Dulbecco's modified Eagle's medium; BSA, bovine serum albumin; CNS, central nervous system; Curc, curcumin; HPLC, high-performance liquid chromatography; LC/MS/MS, liquid chromatography-tandem mass spectrometry; MRM, multiple reaction monitoring; ELISA, enzyme-linked immunosorbent assay; TBS, Tris-buffered saline; GFAP, glial fibrillary acidic protein; ANOVA, analysis of variance; TBS-T, Tris-buffered saline/Tween 20; GI, gastrointestinal; NT, nitrotyrosine; APP, amyloid precursor protein; PC, parent compound.

    • Received February 4, 2008.
    • Accepted April 15, 2008.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 384 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 384, Issue 2
1 Feb 2023
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Curcumin Structure-Function, Bioavailability, and Efficacy in Models of Neuroinflammation and Alzheimer's Disease
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleNEUROPHARMACOLOGY

Curcumin Structure-Function, Bioavailability, and Efficacy in Models of Neuroinflammation and Alzheimer's Disease

Aynun N. Begum, Mychica R. Jones, Giselle P. Lim, Takashi Morihara, Peter Kim, Dennis D. Heath, Cheryl L. Rock, Mila A. Pruitt, Fusheng Yang, Beverly Hudspeth, Shuxin Hu, Kym F. Faull, Bruce Teter, Greg M. Cole and Sally A. Frautschy
Journal of Pharmacology and Experimental Therapeutics July 1, 2008, 326 (1) 196-208; DOI: https://doi.org/10.1124/jpet.108.137455

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleNEUROPHARMACOLOGY

Curcumin Structure-Function, Bioavailability, and Efficacy in Models of Neuroinflammation and Alzheimer's Disease

Aynun N. Begum, Mychica R. Jones, Giselle P. Lim, Takashi Morihara, Peter Kim, Dennis D. Heath, Cheryl L. Rock, Mila A. Pruitt, Fusheng Yang, Beverly Hudspeth, Shuxin Hu, Kym F. Faull, Bruce Teter, Greg M. Cole and Sally A. Frautschy
Journal of Pharmacology and Experimental Therapeutics July 1, 2008, 326 (1) 196-208; DOI: https://doi.org/10.1124/jpet.108.137455
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Substituted tryptamine activity at 5-HT receptors & SERT
  • In Vivo SRI-32743 Attenuates Tat Effects on Extracellular DA
  • Kv7 Opener Attenuates Seizures and Cognitive Deficit
Show more Neuropharmacology

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics