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

doi:10.1016/j.imbio.2008.04.003

Immunobiology

Volume 214, Issue 1, January 2009, Pages 33-39

https://doi.org/10.1016/j.imbio.2008.04.003 Get rights and content

Abstract

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 natural polyphenol, curcumin, in a mouse model of immunologically induced fatigue, where purified lipopolysaccharide (LPS) and Brucella abortus (BA) antigens were used as immunogens. The assessment of chronic fatigue syndrome was based on chronic water-immersion stress test for 10 min 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-α) 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-α 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.

Introduction

The central nervous system (CNS) is extremely susceptible to immunological reactions which occur during disease and injury (Morganti-Kossmann et al., 2002; Lerner et al., 2004). The sensation of fatigue or exhaustion is a prominent symptom in a number of infections and auto-immune diseases and has been a disabling manifestation of certain idiopathic disorders such as chronic fatigue syndrome. Chronic fatigue syndrome is an incapacitating illness defined by disabling chronic fatigue and characteristic accompanying signs (Fukuda et al., 1994; Cleare, 2003). A reduction in daily activity greater than 50% for at least 6 months is a major criterion for the diagnosis of chronic fatigue syndrome (Holmes et al., 1988). Hypotheses about the etiology of chronic fatigue syndrome propose the involvement of a specific bacterial or viral infection and immune dysfunction associated with the infection (Chao et al., 1992; Klimas and Koneru, 2007). Previous research described an immunological model of chronic fatigue syndrome induced by the intraperitoneal administration of bacterial antigen; however, the duration of fatigue evaluated by wheel running was shown to be short (Chao et al., 1992). Ottenweller et al. (1998) have reported the establishment of a mouse model of chronic fatigue syndrome which could be induced by Brucella abortus (BA) administration. A recent report has demonstrated the effectiveness of Hochu-ekki-to (TJ-41), a Japanese herbal medicine for daily running activity in the same model of chronic fatigue syndrome (Wang et al., 2004). In addition, treatment with the BA antigen was known to induce changes in cytokine gene expression in lymphocytes of mice (Svetic et al., 1993).

Endotoxin induces oxidative stress in a variety of organs due to their increased production of reactive oxygen species and a resultant rise in lipid peroxidation (Yoshikawa et al., 1994). It accumulates in tissues rich in cells of the reticulo-endothelial system such as liver and spleen (Sugino et al., 1987). The interaction of lipopolysaccharide (LPS) with macrophages results in the generation of hydrogen peroxide, superoxide anion, hydroxyl radical and singlet oxygen (Sakaguchi and Furusawa, 2006).

In recent years interest has been renewed in multiple activities of natural polyphenols widely distributed in nature. Extensive evidence has accumulated demonstrating potent antioxidant and cytokine inhibitory properties of natural polyphenols such as quercetin, catechin curcumin, etc. (Kawaguchi et al., 2004; Tirkey et al., 2005; Sharma et al., 2006, Sharma et al., 2007). Since the data demonstrating scientific validation of epidemiological claims regarding effectiveness of nutritional supplements for chronic fatigue syndrome is lacking, the present study was designed to evaluate the effect of the natural polyphenol curcumin in a mouse model of immunologically induced fatigue, where purified LPS and BA antigens were used as immunogens.

Section snippets

Animals

Albino Laca mice (20–30 g) bred in the Central Animal House Facility of Panjab University, Chandigarh, India, were used for the study. The animals had free access to standard rodent food pellets and water. They were acclimatized to laboratory conditions one day before the experiment and daily at least for 1 h before the experiment. All the experiments were conducted between 09.00 and 17.00. The experimental protocols were approved by the Institutional Animal Ethics Committee and conducted

Preliminary studies

We studied the effect of LPS per se or BA per se in water-immersion stress on fatigue and hyperalgesia in order to determine their peak effects. For this, mice were administered individually with LPS or BA and the effects were noted on days 1, 2, 4, 7, 10, 14, 17, 19 and 21.

Discussion

Chronic fatigue syndrome is a disease state of obscure etiology associated with multiple symptoms and multiple biochemical or immunological or physiological aberrations. It is now well established that there are complex bi-directional interactions between the CNS and the immune system (Klimas and Koneru, 2007). During an immune response, an important reciprocal relationship between immune products and brain function occurs. This cross talk between the immune system and brain is essential to

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Present study was designed to evaluate antioxidant, immunomodulatory properties of S. oleracea flower to ameliorate CFS infirmity in mice.
In order to induce fatigue, experimental animals were stressed by chronic water – immersion stress model. Meanwhile, parameters like immobility period and tail withdrawal latency were assessed. On the 21st day, mice blood was collected and they were immediately sacrificed for biochemical estimations.
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The outcome of this study indicates ability of SPE in amelioration of CFS by mitigating the oxidative stress and thus provide a powerful combat against CFS which may be due to its antioxidant and immunomodulatory properties.

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

Abstract

Introduction

Section snippets

Animals

Preliminary studies

Discussion

Biochem. Pharmacol.

Clin. Immunol. Immunopathol.

Arch. Biochem. Biophys.

Psychoneuroendocrinology

Biochem. Biophys. Commun.

Am. J. Med.

Physiol. Behav.

Med. Hypoth.

J. Neuroimmunol.

Life Sci.

Function and activation of NF-kappa B in the immune system

Annu. Rev. Immunol.

The neuroendocrinology of chronic fatigue syndrome

Endocr. Rev.

Curcumin (diferuloylmethane) a singlet oxygen quencher

Biochem. Biophys. Res.

The sympathetic nerve – an integrative interface between two supersystems: the brain and the immune system

Pharmacol. Rev.

Muscle-derived ROS and thiol regulation in muscle fatigue

J. Appl. Physiol.

The chronic fatigue syndrome: a comprehensive approach to its definition and study

Ann. Intern. Med.

Chronic fatigue syndrome: a working case definition

Ann. Intern. Med.

Lipopolysaccharide-mediated immobility in mice: reversal by cyclooxygenase enzyme inhibitors

Methods Findings Exp. Clin. Pharmacol.

Salmonella lipopolysaccharide (LPS) mediated neurodegeneration in hippocampal slice cultures

Neurotox. Res.

Endotoxin induced local inflammation and hyperalgesia in rats mince, a new model for inflammatory pain

Pharmacology

Reversal of LPS-induced central and peripheral hyperalgesia by green tea extract

Phytother. Res.

Chronic fatigue syndrome: inflammation, immune function and neuroendocrine interactions

Curr. Rheumatol. Rep.