Inhibition of hemozoin-induced neuroinflammation by medicinal plants used for the treatment of malaria in Southwest Nigeria: implications for cerebral malaria

Abstract This study aimed to investigate some antimalarial plants for effects on neuroinflammation. Freeze-dried infusions of the plants were investigated for effects on hemozoin-induced neuroinflammation in BV-2 microglia and levels of inflammatory mediators measured. Alstonia boonei (stem bark), Anacardium occidentale (stem bark), Azadiractha indica (leaves), Enantia chlorantha (stem bark), Khaya senegalensis (stem bark), Mangifera indica (stem bark), and Nauclea latifolia (stem bark) produced significant (p<0.05) reduction in TNFα, IL-6, IL-1β, MCP-1, RANTES and iNOS/NO production in BV-2 microglia stimulated with a synthetic hemozoin (400 µg/mL). Further experiments showed that pre-treatment with 50 µg/mL of A. boonei, A. indica, A. occidentale, E. chlorantha and M. indica prior to hemozoin stimulation resulted in inhibition of NF-κB activation by >40%, while E. chlorantha, K. senegalensis and N. latifolia produced weak activities. Pretreatment with A. indica (50 µg/mL) produced the highest inhibition (58.6%) of hemozoin-induced increased NLRP3 protein expression, while A. occidentale (50 µg/mL), M. indica (50 µg/mL) and A. boonei (50 µg/mL) reduced expression by 54.1%, 49.2% and 47.1%, respectively. Hemozoin-induced increased caspase-1 activity was reduced by A. boonei, A. occidentale, A. indica, E. chlorantha, and M. indica. These results suggest that A. boonei, A. occidentale, A. indica and M. indica produced strong inhibition of hemozoin-induced neuroinflammation through mechanisms involving NFκB and NLRP3 inflammasome activation, while moderate activities were produced by E. chlorantha, K. senegalensis and N. latifolia. The outcome of the study provides pharmacological evidence for the potential benefits of the plants as herbal treatments of cerebral malaria symptoms.