Figure 2From: The plant-based immunomodulator curcumin as a potential candidate for the development of an adjunctive therapy for cerebral malariaSchematic diagram illustrating the main biological targets of curcumin that can be exploited in suppressing immunopathological events associated with cerebral malaria. Upon exposure of cells to curcumin, a transient induction of reactive oxygen species (ROS) may occur. This potentially leads to activation of a signalling cascade involving the peroxisome proliferator activated receptor gamma (PPARγ) and induction of the redox-sensitive factor Nrf2. Activated-Nrf2 and PPARγ translocate in the nucleus, where they bind to their target genes via their respective binding sites,the anti-oxidant response element (ARE) for Nrf2 and the peroxisome proliferator response element (PPRE) for PPARγ. In monocytes/macrophages activation of Nrf2 or PPARγ will lead to upregulation of the surface expression of CD36, increasing their phagocytic activity [55]. In other cell types such as endothelial cells, activation of Nrf2 and PPARγ may lead to upregulation of cytoprotective enzymes [haem oxygenase 1 (HO-1), NADPH quinine oxidoreductase-1 (NQ-1), gamma-glutamate cysteine ligase (γ-GCL)], counteracting free radical-induced damage and exerting a neuroprotective effect [87]. On the other hand, PPARγ (solid arrows) and perhaps Nrf2 (dashed arrows) could exert their anti-inflammatory activities by inhibiting NF-κB activation, thereby downregulating proinflammatory cytokine responses and adhesion molecule expression which are all implicated in the pathology of CM.Back to article page