Resveratrol, Found in Red Wine, Worsens MS-Like Symptoms and Neuropathology in Mice
Researchers discourage supplemental use by
patients with multiple sclerosis, according to report in The American Journal
Researchers discourage supplemental use by patients with multiple sclerosis, according to report in The American Journal of Pathology
Philadelphia, PA, October 1, 2013
Resveratrol, a naturally occurring polyphenol compound
produced by the skin of red grapes and peanuts, and found in red wine, has been
touted as a beneficial supplement due to its anti-inflammatory and antioxidant
properties. This has been supported by some experimental studies, whereas
others suggest a lack of benefit. A new study using two multiple sclerosis (MS)
models published in The American Journal
of Pathology has found that resveratrol actually worsened MS-like
neuropathology and inflammation and had no neuroprotective effects.
"Resveratrol may have detrimental effects in some disease conditions and should be discouraged for supplemental use by MS patients pending further research," says lead investigator Ikuo Tsunoda, MD, PhD, Assistant Professor in the Department of Microbiology and Immunology, Center for Molecular & Tumor Virology of the Louisiana State University Health Sciences Center, Shreveport, LA.
Investigators (Fumitaka Sato, PhD, et al) tested resveratrol in autoimmune and viral models of MS. In the autoimmune model, experimental autoimmune encephalomyelitis (EAE) was induced in 6-week-old mice using myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide. Mice were fed either a control diet or a diet containing resveratrol for 2 months or only during the early (days -1 to 8) or the late (days 14 to 23) phases of EAE. Around 12 days after MOG sensitization, all groups started to develop clinical signs, such as tail and hind limb paralysis, and the symptoms worsened and peaked by 3 weeks. After 5 weeks, mice fed the control diet showed either complete recovery or mild paralysis, but all three groups fed resveratrol exhibited severe and lasting EAE without remission.
Spinal cord neuropathology showed higher pathology scores in demyelination, meningitis, perivascular cuffing (inflammation), and overall pathology in mice that had been given resveratrol during the early phase compared with mice fed a control diet, whereas mice treated with resveratrol during the entire treatment period had significantly higher pathology scores in meningitis and overall pathology than controls. Groups did not differ in brain pathology scores.
Although it has been suggested that resveratrol has anti-inflammatory properties, in this study resveratrol did not suppress autoimmune responses as measured by levels of MOG35-55-specific lymphoproliferative responses and pro-inflammatory cytokine production.
To see whether resveratrol had anti-viral properties, as has been reported, 5-week-old mice were infected intracerebrally with the Daniels (DA) strain of Theiler's murine encephalomyelitis virus (TMEV) to induce TMEV-induced demyelinating disease (TMEV-IDD). The mice were fed either a control diet or one containing resveratrol from days 35 to 48 (the chronic phase). Similar to the findings from the EAE model, mice treated with resveratrol developed significantly more severe TMEV-IDD compared with the controls. Another study using the GDVII strain of TMEV to see whether resveratrol could suppress neurodegeneration caused by direct viral infection, not by immunopathology, found that resveratrol had no neuroprotective activity against the virus.
"Resveratrol did not show anti-viral effects in TMEV infection," says Dr. Tsunoda, although he notes that resveratrol has been shown by others to have anti-viral effects on some viruses related to MS, such as herpes simplex virus and Epstein-Barr virus.
To explain their findings, the authors suggest that resveratrol's vasodilating effects via endothelial cells might enhance infiltration of inflammatory cells into the central nervous system, which in turn might play a key role in the pathogenesis of MS.
The degree to which resveratrol exacerbated demyelination and inflammation surprised the research team. "Our findings illustrate that caution should be exercised for potential therapeutic application of resveratrol in human inflammatory demyelination diseases, including MS," says Dr. Tsunoda.
# # #
Notes for editors
"Resveratrol Exacerbates Both Autoimmune and Viral Models for Multiple Sclerosis," by Fumitaka Sato, Nicholas E. Martinez, Maira Shahid, John W. Rose, Noel G. Carlson, and Ikuo Tsunoda. (http://dx.doi.org/10.1016/j.ajpath.2013.07.006). It appears in The American Journal of Pathology, Volume 183, Issue 5 (November 2013) published by Elsevier.
Full text of the article is available to credentialed journalists upon request; contact Eileen Leahy at +1 732 238 3628 or firstname.lastname@example.org. Journalists wishing to interview the authors should contact Ikuo Tsunoda, MD, PhD, at +1 318 675 5757 or email@example.com, or Sally Croom, Executive Director, Communications and Public Affairs, Louisiana State University Health Sciences Center, at firstname.lastname@example.org.
About The American Journal Of Pathology
The American Journal of Pathology (http://ajp.amjpathol.org), official journal of the American Society for Investigative Pathology, seeks to publish high-quality, original papers on the cellular and molecular biology of disease. The editors accept manuscripts that advance basic and translational knowledge of the pathogenesis, classification, diagnosis, and mechanisms of disease, without preference for a specific analytic method. High priority is given to studies on human disease and relevant experimental models using cellular, molecular, animal, biological, chemical, and immunological approaches in conjunction with morphology.
The leading global forum for reporting quality original research on cellular and molecular mechanisms of disease, The American Journal of Pathology is the most highly cited journal in Pathology – over 38,000 cites in 2012 – with an Impact Factor of 4.522 and Eigenfactor of 0.07599 according to the 2012 Journal Citation Reports®, Thomson Reuters, and an H index of 181 according to the 2011 SCImago Journal and Country Rank.
Elsevier is a global information analytics business that helps scientists and clinicians to find new answers, reshape human knowledge, and tackle the most urgent human crises. For 140 years, we have partnered with the research world to curate and verify scientific knowledge. Today, we’re committed to bringing that rigor to a new generation of platforms. Elsevier provides digital solutions and tools in the areas of strategic research management, R&D performance, clinical decision support, and professional education; including ScienceDirect, Scopus, SciVal, ClinicalKey and Sherpath. Elsevier publishes over 2,500 digitized journals, including The Lancet and Cell, 39,000 e-book titles and many iconic reference works, including Gray's Anatomy. Elsevier is part of RELX, a global provider of information-based analytics and decision tools for professional and business customers. www.elsevier.com