Saturated anacardic acid shows promise as adjuvant therapy for preventing severe malaria via attenuation of inflammatory response by modulation of the NF-κB pathway.

Malaria represents a major global health challenge. Excessive activation of inflammatory response is critical for the pathogenesis of severe malaria. The NF-κB signaling pathway regulates inflammatory responses; saturated anacardic acid (SAA) inhibits NF-κB activation. The aim of this study was to evaluate whether SAA modulated inflammatory mediators in BV-2 microglia and THP-1 monocytes, whose overproduction contributes to the development of severe malaria. Survival rate was assessed in cerebral malaria-susceptible CBA mice infected with Plasmodium berghei ANKA and treated or not with SAA. THP-1 monocytes and BV-2 microglia were incubated with or without SAA and with or without co-incubation with P. falciparum or P. berghei ANKA, respectively. After 24 h, terminal molecules of the NF-κB pathway RelA and RelB, TNF-α, IL-6, IL-8, MCP-1, ROS, NO, COX-2 and 5-LOX were assessed by flow cytometry. SAA increased survival in P. berghei-Infected CBA mice. BV-2 microglia exhibited higher RelB expression than THP-1 monocytes. Co-incubation with Plasmodium and SAA decreased RelB but increased RelA expression in BV-2 microglia, whereas RelA expression increased in THP-1 monocytes. Co-incubation with SAA and Plasmodium decreased TNF-α, IL-8, MCP-1, ROS, NO, and COX-2 expression but increased IL-6 production, all of which are associated with inflammatory responses involved in severe malaria. To our knowledge, this study is the first to demonstrate that SAA modulates the key components of severe malaria immunopathogenesis, particularly TNF-α production, ROS and NO generation in BV-2 microglia and THP-1 monocytes. These findings indicate that SAA may represent a promising adjunct therapy to prevent progression to severe malaria.