Effectivity Of Annona Muricata and Artemisinin Combined Therapy on Brain CXCL10 expression (Study in Swiss Mice During Severe Plasmodium Berghei ANKA Infection)

ABSTRACT Background: Malaria, caused by Plasmodium sp infection, is a major global cause of morbidity and mortality. Most experimental cerebral malaria (ECM) studies show increase number of Th1 cells and CTLs in the brain, due to increase chemokine expression, including CXCL10, a potent chemokine involved in cerebral malaria (CM). Recent studies show that CXCL10 provokes apoptosis of human brain micro-endothelial cells and in vitro neuroglia cells. Objective: To determine whether combination of Annona muricata -leaf-extracted-by-water (AME) and artemisinin-combination-therapy (ACT) reduce brain-CXCL10-expression of Swiss-mice inoculated with P. berghei ANKA (PbA) . Methods: This was an experimental-study with post-test-only-control-group-design. Twenty-four Swiss-mice (PbA-inoculated) were randomly divided into 4 groups. Control group (C) was PbA inoculated only. X 1, X 2 and X 3 groups received AME, ACT and combination of AME and ACT treatment, respectively.  CXCL10 was stained with in immunohistochemistry, which then observed by light microscope in order to determine Allred-score. Kruskal-Wallis test was used to statistically analyze the differences among groups, then followed by a Mann- Whitney U test. Result: C and X 1 groups had severe-PbA-infection when the study was end on day-7-PbA-infection, while X 2 and X 3 groups entered recovery-stage. The AME-ACT-treatment-group had significantly lower of brain-CXCL10-expression than AME-group ( p =0.008) and nearly significantly lower than control-group ( p =0.058). Group that received ACT alone had no different value of brain-CXCL10-expression than control-group ( p =0.502) and combination AME–ACT group ( p =0.335). Conclusion: The combination of AME–ACT treatment decreases brain-CXCL10-expression of Swiss-mice during PbA-infection-recovery-stage, indicating the effectivity of AME–ACT combined therapy is better prevention of cerebral malaria than AME alone.