Annona muricata leaf water extract in combination with artemisinin-based combination therapy for increasing CCL19 levels in the treatment of severe Plasmodium berghei ANKA infection using swiss mice

Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection, with resistance to antimalarial drugs, including artemisinin-based combination therapies(ACTs), posing a significant threat. CD4+ naive cells expressing CCR7 are known to play a protective role, as they readily migrate to secondary lymphoid tissues activated by CCL19 chemokines. In an effort to address this challenge, we investigated the impact of Annona muricata, an herbaceous and immunomodulatory plant, on CCL19 concentration. We conducted experiments on 24 mice, dividing them into four groups: one control group and three treatment groups. Groups 1 and 3 received a daily dose of 4.68 mg of Annona muricata leaf water extract (AM) for seven days before CM infection. After seven days of treatment, all groups were infected with CM. Groups 1 and 3 continued with a 9.36 mg AM dosage for an additional seven days, while groups 2 and 3 received a 0.819 mg ACTs dosage on the fourth day post-infection. We analyzed the CCL19 content in the mice's spleens and evaluated the data using Bonferroni post hoc, Kruskal-Wallis, and Mann-Whitney U tests. Our results demonstrated that the CCL19 levels in the AM-ACTs group significantly surpassed those in both the control group (p = 0.009) and the ACTs group (p = 0.002). This suggests that the combination of AM and ACTs led to a notable increase in CCL19 levels in Swiss mice afflicted with CM. While further research is necessary to validate and expand upon these findings, our study highlights the potential of AM to enhance CCL19 production, potentially facilitating the migration of naive T cells and reinforcing the immune response.