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Background  The development of  Plasmodium  resistance to the last effective anti-malarial drugs necessitates the urgent development of new anti-malarial therapeutic strategies. To this end, plants are an important source of new molecules. The objective of this study was to evaluate the anti-malarial effects of  Terminalia albida , a plant used in Guinean traditional medicine, as well as its anti-inflammatory and antioxidant properties, which may be useful in treating cases of severe malaria.    Methods  In vitro antiplasmodial activity was evaluated on a chloroquine-resistant strain of  Plasmodium falciparum  (K-1). In vivo efficacy of the plant extract was measured in the experimental cerebral malaria model based on  Plasmodium berghei  (strain ANKA) infection. Mice brains were harvested on Day 7–8 post-infection, and T cells recruitment to the brain, expression levels of pro- and anti-inflammatory markers were measured by flow cytometry, RT-qPCR and ELISA. Non-malarial in vitro models of inflammation and oxidative response were used to confirm  Terminalia albida  effects. Constituents of  Terminalia albida  extract were characterized by ultra‐high performance liquid chromatography coupled with high resolution mass spectrometry. Top ranked compounds were putatively identified using plant databases and in silico fragmentation patterns.    Results  In vitro antiplasmodial activity of  Terminalia albida  was confirmed with an IC50 of 1.5 μg/mL. In vivo,  Terminalia albida  treatment greatly increased survival rates in  P. berghei -infected mice. Treated mice were all alive until Day 12, and the survival rate was 50% on Day 20.  Terminalia albida  treatment also significantly decreased parasitaemia by 100% on Day 4 and 89% on Day 7 post-infection. In vivo anti-malarial activity was related to anti-inflammatory properties, as  Terminalia albida  treatment decreased T lymphocyte recruitment and expression of pro-inflammatory markers in brains of treated mice. These properties were confirmed in vitro in the non-malarial model. In vitro,  Terminalia albida  also demonstrated a remarkable dose-dependent neutralization activity of reactive oxygen species. Twelve compounds were putatively identified in  Terminalia albida  stem bark. Among them, several molecules already identified may be responsible for the different biological activities observed, especially tannins and triterpenoids.    Conclusion  The traditional use of  Terminalia albida  in the treatment of malaria was validated through the combination of in vitro and in vivo studies.

malaria journal

Terminalia albida treatment improves survival in experimental cerebral malaria through reactive oxygen species scavenging and anti-inflammatory properties