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Curcumin, a polyphenolic antioxidant, attenuates chronic fatigue syndrome in murine water immersion stress model.

Journal: Immunobiology. 2009;214(1):33-9. Epub 2008 Jun 17.
Authors: Gupta A, Vij G, Sharma S, Tirkey N, Rishi P, Chopra K.
Affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
NLM Citation: PMID: 19159825

Chronic fatigue syndrome, infection and oxidative stress are interrelated in epidemiological case studies. However, data demonstrating scientific validation of epidemiological claims regarding effectiveness of nutritional supplements for chronic fatigue syndrome are lacking. This study is designed to evaluate the effect of polyphenolic antioxidant, curcumin, in a mouse model of immunologically induced fatigue, where purified lipopolysaccharide (LPS)[gram-negative bacteria] and Brucella abortus (BA)[gram-negative bacterium] antigens were used as immunogens.

The assessment of chronic fatigue syndrome was based on chronic water-immersion stress test for 10min daily for 19 days and the immobility time was taken as the marker of fatigue.

Mice challenged with LPS or BA for 19 days showed significant increase in the immobility time and hyperalgesia on day 19, as well as marked increase in serum tumor necrosis factor-alpha (TNF-alpha) levels. Concurrent treatment with curcumin resulted in significantly decreased immobility time as well as hyperalgesia. There was significant attenuation of oxidative stress as well as TNF-alpha levels.

These findings strongly suggest that during immunological activation, there is significant increase in oxidative stress and curcumin can be a valuable option in the treatment of chronic fatigue syndrome.

Note that the chronic fatigue syndrome here is immunologically induced fatigue. Given that both immunogens were bacterial and that this therapeutic option is during immunological activation, maybe postinfectious fatigue syndrome(Oxford Criteria) might be more accurate. Which ever name, we still have the FATIGUE word.

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Curcumin is the principal curcuminoid of the popular Indian curry spice turmeric, the other two curcuminoids being desmethoxycurcumin and bis-desmethoxycurcumin. The curcuminoids are polyphenols and are responsible for the yellow color of turmeric. Curcumin can exist in at least two tautomeric forms, keto and enol. The enol form is more energetically stable in the solid phase and in solution. (en.wikipedia.org/wiki/Curcumin)

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Other Studies

Jiao Y, Wilkinson J, Di X, et al (January 2009).
"Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator". Blood 113 (2): 462–9. doi:10.1182/blood-2008-05-155952. PMID 18815282.

Blood. 2009 Jan 8;113(2):462-9. Epub 2008 Sep 24.

Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator.

Jiao Y, Wilkinson J 4th, Di X, Wang W, Hatcher H, Kock ND, D'Agostino R Jr, Knovich MA, Torti FM, Torti SV.
Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

Curcumin is a natural product currently in human clinical trials for a variety of neoplastic, preneoplastic, and inflammatory conditions. We previously observed that, in cultured cells, curcumin exhibits properties of an iron chelator. To test whether the chelator activity of curcumin is sufficient to induce iron deficiency in vivo, mice were placed on diets containing graded concentrations of both iron and curcumin for 26 weeks. Mice receiving the lowest level of dietary iron exhibited borderline iron deficiency, with reductions in spleen and liver iron, but little effect on hemoglobin, hematocrit, transferrin saturation, or plasma iron. Against this backdrop of subclinical iron deficiency, curcumin exerted profound 2 effects on systemic iron, inducing a dose-dependent decline in hematocrit, hemoglobin, serum iron, and transferrin saturation, the appearance of microcytic anisocytotic red blood cells, and decreases in spleen and liver iron content. Curcumin repressed synthesis of hepcidin, a peptide that plays a central role in regulation of systemic iron balance. These results demonstrate that curcumin has the potential to affect systemic iron metabolism, particularly in a setting of subclinical iron deficiency. This may affect the use of curcumin in patients with marginal iron stores or those exhibiting the anemia of cancer and chronic disease.

Previously in BMC Medical Genomics 2009 "..inappropriate Iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases"

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Kutluay SB, Doroghazi J, Roemer ME, Triezenberg SJ (January 2008).
"Curcumin inhibits herpes simplex virus immediate-early gene expression by a mechanism independent of p300/CBP histone acetyltransferase activity".
Virology 373: 239. doi:10.1016/j.virol.2007.11.028. PMID 18191976.

Virology. 2008 Apr 10;373(2):239-47. Epub 2008 Jan 14.

Curcumin inhibits herpes simplex virus immediate-early gene expression by a mechanism independent of p300/CBP histone acetyltransferase activity.

Kutluay SB, Doroghazi J, Roemer ME, Triezenberg SJ.
Graduate Program in Cell and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.

Curcumin, a phenolic compound from the curry spice turmeric, exhibits a wide range of activities in eukaryotic cells, including antiviral effects that are at present incompletely characterized. Curcumin is known to inhibit the histone acetyltransferase activity of the transcriptional coactivator proteins p300 and CBP, which are recruited to the immediate early (IE) gene promoters of herpes simplex virus type 1 (HSV-1) by the viral transactivator protein VP16. We tested the hypothesis that curcumin, by inhibiting these coactivators, would block viral infection and gene expression. In cell culture assays, curcumin significantly decreased HSV-1 infectivity and IE gene expression. Entry of viral DNA to the host cell nucleus and binding of VP16 to IE gene promoters was not affected by curcumin, but recruitment of RNA polymerase II to those promoters was significantly diminished. However, these effects were observed using lower curcumin concentrations than those required to substantially inhibit global H3 acetylation. No changes were observed in histone H3 occupancy or acetylation at viral IE gene promoters. Furthermore, p300 and CBP recruitment to IE gene promoters was not affected by the presence of curcumin. Finally, disruption of p300 expression using a short hairpin RNA did not affect viral IE gene expression. These results suggest that curcumin affects VP16-mediated recruitment of RNA polymerase II to IE gene promoters by a mechanism independent of p300/CBP histone acetyltransferase activity.

PMID: 18191976 [PubMed - indexed for MEDLINE]

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Bourne KZ, Bourne N, Reising SF, Stanberry LR (1999 July).
"Plant products as topical microbicide candidates: assessment of in vitro and in vivo activity against herpes simplex virus type 2".
Antiviral research 42 (3): 219–26. doi:10.1016/S0166-3542(99)00020-0. PMID 10443534.

Antiviral Res. 1999 Jul;42(3):219-26.

Plant products as topical microbicide candidates: assessment of in vitro and in vivo activity against herpes simplex virus type 2.

Bourne KZ, Bourne N, Reising SF, Stanberry LR.
Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, OH 45229-3039, USA.

There is considerable interest in developing topical microbicides; products to be used intravaginally by women for protection against sexually transmitted diseases. Many compounds derived from plants have been shown to have antimicrobial properties. We examined 19 such compounds in vitro by plaque reduction assay to determine their activity against a common sexually transmitted pathogen, herpes simplex virus type 2. Compounds with an ED50 < or = 7.0 mg/ml were tested for efficacy in vivo. Four compounds, carrageenan lambda type IV, cineole, curcumin, and eugenol, provided significant protection (P < 0.05) in a mouse model of intravaginal HSV-2 challenge. Eugenol, which provided the greatest protection in mice was also evaluated using the guinea pig model of genital HSV-2 infection where it also demonstrated significant protection. Based on these results, several plant-derived compounds appear to warrant further evaluation as potential microbicides.

PMID: 10443534 [PubMed - indexed for MEDLINE]

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