In vivo validation of anti-malarial activity of crude extracts of Terminalia macroptera, a Malian medicinal plant

Abstract

BackgroundPlasmodium 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.MethodsTerminalia 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.ResultsLethal 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.ConclusionsThis study confirms both safety and anti-malarial activity of T. macroptera, thus validating its traditional use.

In Vivo Antimalarial Activity of 80% Methanol and Aqueous Bark Extracts of Terminalia brownii Fresen. (Combretaceae) against Plasmodium berghei in Mice

“…Both extracts of the plant prolonged the mean survival time of the experimental mice indicating that the plant suppressed P. berghei and reduced the overall pathologic effect of the parasite on mice. Similar result on mean survival time of mice was reported in studies conducted on T. chebula, T. bellerica [31], and T. macroptera [32].…”

“…Based on the above classification, the plant is considered to have exhibited a good antiplasmodial activity. is assertion is evidenced by other in vivo studies that reported antimalarial activity of other species of the same genus such as T. chebula, T. bellerica [31], and T. macroptera [32].…”

Evaluation of Anti-inflammatory, Anti-pyretic, Analgesic, and Hepatoprotective Properties of Terminalia macroptera

“…At present, the following chemical labelling and classification of acute systemic toxicity, based on oral LD 50 values, are from the recommendations of the Globally Harmonized System of Classification [OECD, 2008], and ranked as: very toxic, ≤ 5 mg/kg; toxic, > 5 ≤ 50 mg/kg; harmful, > 50 ≤ 500 mg/kg; and no label, > 500 ≤ 2000 mg/ kg [4]. In our previous work [3], oral administration of TML and TMR at a dose of 2000 mg/kg did not cause mortality among experimental animals. This indicates that the LD 50 s of TML and TMR are…”

“…2 Ten samples as sold. 3 Registration form of the manufacturer and memoranda of understanding between the manufacturer and a research institution. 4 Complete monograph(s) of the plant's component(s).…”

“…In a recent study, our team demonstrated the ability of T. macroptera roots (TMR) and leaves (TML) to limit Plasmodium parasitemia and to increase survival in two murine models of uncomplicated and cerebral malaria, respectively. In addition, we demonstrated that according to the Organization for Economic Cooperation and Development's (OECD) Globally Harmonized System of Classification, both extracts were non-toxic orally [3]. The same batch of T. macroptera was used in both studies.…”