In vivo validation of anti-malarial activity of crude extracts of Terminalia macroptera, a Malian medicinal plant.
BACKGROUND
Plasmodium falciparum malaria is still one of the most deadly pathology worldwide. Efficient treatment is jeopardized by parasite resistance to artemisinin and its derivatives, and by poor access to treatment in endemic regions. Anti-malarial traditional remedies still offer new tracks for identifying promising antiplasmodial molecules, and a way to ensure that all people have access to care. The present study aims to validate the traditional use of Terminalia macroptera, a Malian plant used in traditional medicine.


METHODS
Terminalia macroptera was collected in Mali. Leaves (TML) and roots ethanolic extracts (TMR) were prepared and tested at 2000 mg/kg for in vivo acute toxicity in Albino Swiss mice. Antiplasmodial activity of the extracts was assessed against a chloroquine resistant strain P. falciparum (FcB1) in vitro. In vivo, anti-malarial efficacy was assessed by a 4-day suppressive test at 100 mg/kg in two malaria murine models of uncomplicated malaria (Plasmodium chabaudi chabaudi infection) and cerebral malaria (Plasmodium berghei strain ANKA infection). Constituents of TMR were characterized by ultra-high-performance liquid chromatography coupled to high resolution mass spectrometry. Top ranked compounds were putatively identified using plant databases and in silico fragmentation pattern.


RESULTS
Lethal dose of TML and TMR were greater than 2000 mg/kg in Albino Swiss mice. According to the OECD's Globally Harmonized System of Classification, both extracts are non-toxic orally. Antiplasmodial activity of T. macroptera extracts was confirmed in vitro against P. falciparum FcB1 strain with IC50 values of 1.2 and 1.6 µg/mL for TML and TMR, respectively. In vivo, oral administration of TML and TMR induced significant reduction of parasitaemia (37.2 and 46.4% respectively) in P. chabaudi chabaudi infected mice at the 7th day of infection compared to untreated mice. In the cerebral malaria experimental model, mice treated with TMR and TML presented respectively 50 and 66.7% survival rates at day 9 post-infection when all untreated mice died. Eleven major compounds were found in TMR. Among them, several molecules already known could be responsible for the antiplasmodial activity of the roots extract of T. macroptera.


CONCLUSIONS
This study confirms both safety and anti-malarial activity of T. macroptera, thus validating its traditional use.
['Haidara|Mahamane|M|', 'Haddad|Mohamed|M|', 'Denou|Adama|A|', 'Marti|Guillaume|G|', 'Bourgeade-Delmas|Sandra|S|', 'Sanogo|Rokia|R|', 'Bourdy|Geneviève|G|', 'Aubouy|Agnès|A|http://orcid.org/0000-0003-2265-4972']
D000818:Animals D000962:Antimalarials D005260:Female D008302:Mali D008519:Medicine, Traditional D051379:Mice D010936:Plant Extracts D018515:Plant Leaves D018517:Plant Roots D010946:Plants, Medicinal D010962:Plasmodium berghei D016788:Plasmodium chabaudi D029766:Terminalia D023382:Toxicity Tests, Acute
Terminalia macroptera Toxicity In vitro Plasmodium chabaudi Antimalarial activity Mice models Plasmodium berghei ANKA