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Terminalia albida treatment improves survival in experimental cerebral malaria through reactive oxygen species scavenging and anti-inflammatory properties
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Terminalia albida treatment improves survival in experimental cerebral malaria through reactive oxygen species scavenging and anti-inflammatory properties
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Journal Article
Terminalia albida treatment improves survival in experimental cerebral malaria through reactive oxygen species scavenging and anti-inflammatory properties
2019
Overview
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.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Animals
/ Anti-Inflammatory Agents - pharmacology
/ Antimalarials - pharmacology
/ Bark
/ Biomedical and Life Sciences
/ Brain
/ ELISA
/ Experimental cerebral malaria
/ Female
/ High performance liquid chromatography
/ HPLC
/ Malaria
/ Malaria, Cerebral - prevention & control
/ Mice
/ Oxygen
/ Plant Extracts - pharmacology
/ Plasmodium berghei - drug effects
/ Plasmodium falciparum - drug effects
/ Rankings
/ Reactive Oxygen Species - pharmacology
/ Survival
/ T cells
