title: The plant-based immunomodulator curcumin as a potential candidate for the development of an adjunctive therapy for cerebral malaria.
abstract: The clinical manifestations of cerebral malaria (CM) are well correlated with underlying major pathophysiological events occurring during an acute malaria infection, the most important of which, is the adherence of parasitized erythrocytes to endothelial cells ultimately leading to sequestration and obstruction of brain capillaries. The consequent reduction in blood flow, leads to cerebral hypoxia, localized inflammation and release of neurotoxic molecules and inflammatory cytokines by the endothelium. The pharmacological regulation of these immunopathological processes by immunomodulatory molecules may potentially benefit the management of this severe complication. Adjunctive therapy of CM patients with an appropriate immunomodulatory compound possessing even moderate anti-malarial activity with the capacity to down regulate excess production of proinflammatory cytokines and expression of adhesion molecules, could potentially reverse cytoadherence, improve survival and prevent neurological sequelae. Current major drug discovery programmes are mainly focused on novel parasite targets and mechanisms of action. However, the discovery of compounds targeting the host remains a largely unexplored but attractive area of drug discovery research for the treatment of CM. This review discusses the properties of the plant immune-modifier curcumin and its potential as an adjunctive therapy for the management of this complication.
authors.affiliation: Faculty of Infectious and Tropical Diseases, Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK. patmimche@hotmail.com
authors.forename: Patrice N
authors.initials: PN
authors.lastname: Mimche
authors.forename: Donatella
authors.initials: D
authors.lastname: Taramelli
authors.forename: Livia
authors.initials: L
authors.lastname: Vivas
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000962:Antimalarials / Q000627:therapeutic use*; D003474:Curcumin / Q000627:therapeutic use*; D019587:Dietary Supplements; D004359:Drug Therapy, Combination; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008288:Malaria / Q000188:drug therapy / Q000276:immunology; D016779:Malaria, Cerebral / Q000188:drug therapy* / Q000276:immunology; D010944:Plants / Q000737:chemistry*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000962:Antimalarials; D007155:Immunologic Factors; D003474:Curcumin