Abstract:This review is an attempt to summarize our current understanding of curcumin's potential as a neuroprotectant and an antidepressant. This dual property confers a unique advantage to this herbal medication, believed to be devoid of any major side effects, to combat commonly observed co-morbid conditions of a neurodegenerative and a neuropsychiatric disorder. Moreover, in line with the theme of this series, the role of inflammation and stress in these diseases and possible anti-inflammatory effects of curcumin, as well as its interaction with signal transduction proteins as a common denominator in its varied mechanisms of action, are also discussed. Thus, following a brief introduction of curcumin's pharmacology, we present research suggesting how its anti-inflammatory properties have therapeutic potential in treating a devastating neurological disorder (Parkinson's disease = PD) and a debilitating neuropsychiatric disorder (major depressive disorder = MDD). It is concluded that curcumin, or better yet, an analog with better and longer bioavailability could be of important therapeutic potential in PD and/or major depression. CurcuminCurcumin, a diarylheptanoid, is the principal curcuminoid of the popular South Asian spice turmeric (Curcuma longa), which is a member of the ginger family (Zingiberaceae). Curcumin and turmeric's other two curcuminoids, desmethoxycurcumin and bisdesmethoxycurcumin are natural phenols responsible for the yellow color of turmeric. Indeed, because of its bright-yellow color, curcumin is used as a food coloring as well as food additive. Curcumin can exist in several tautomeric forms, however, the enol form is more stable in the solid phase and in solution [1].Curcumin's antioxidant [2][3][4], hepato-and nephroprotectant [5][6][7], antimicrobial [8,9], anti-inflammatory [10-13] and potential anti-depressant properties [14][15][16][17][18][19] are well documented. Epidemiological studies have demonstrated that societies that widely use curcumin show reduced incidence of inflammation-influenced and cognitive function diseases such as Alzheimer's disease [20][21][22][23]. It has also been suggested that curcumin may reduce the incidence of Parkinson's disease (PD), as some studies have shown an absence of age-related changes in nigral dopaminergic neurons in Indian populations that consume large amounts of curcumin [24][25][26]. Moreover, as discussed below, numerous in vitro and in vivo studies provide substantial evidence for a protective effect of curcumin against insults that may precipitate PD-like symptoms. Depression General ConsiderationsMajor depression is a disorder with many definitions and manifestations and with a 12-month prevalence rate of 6.3% to 10.3% in Western societies [27]. Symptoms may vary, but often include anhedonia, disrupted sleep patterns, lack of motivation, or emotional distress (e.g., anxiety). Although a number of clinically effective treatments are available, a large segment of patients are non-responsive (i.e., exhibit treatment-resistance to first-...

Parkinson’s disease (PD) is a debilitating neurodegenerative disorder that results from the loss of or damage to dopaminergic cells in the substantia nigra. Exposure to either the pesticide rotenone or the endogenous neurotoxin salsolinol has been shown to mimic this dopaminergic cell loss. In this study we first sought to determine whether combination of rotenone and salsolinol would result in an additive or synergistic toxicity. For this purpose we utilized SH-SY5Y cells, a human neuroblastoma cell line that is commonly used to model dopaminergic neurodegeneration. We then tested whether curcumin, a natural plant compound with known health benefits including potential neuroprotective properties, could also protect against rotenone and/or salsolinol induced toxicity. Moreover, since apoptotic mechanism has been implicated in toxicity of these compounds the anti-apoptotic effect of curcumin was also evaluated. Our results indicate a synergistic toxicity of low concentrations of rotenone (1 and 5 uM) and salsolinol (25 and 50 mM) that was associated with apoptosis as determined by cell flow cytometry. There was also an increase in caspase-3 levels. Pretreatment with curcumin (1-10 uM) dose-dependently attenuated rotenone and/or salsolinol induced toxicity and the associated apoptosis. These results suggest that exposure to a combination of rotenone and salsolinol may contribute to the pathology of PD, and that curcumin has a therapeutic potential in this disease.