Antimalarial effects of Eugenia ancorifera hydroethanolic leaf extract: Integrating in vitro, in vivo and in silico studies
Loïc Ngwem Tenlep, Raceline Gounoue Kamkumo, Florence Ngueguim Tsofack, Patrick Valère Tsouh Fokou, Noella Molisa Efange, Pascal Emmanuel Owona and 6 more
Clinical Traditional Medicine and Pharmacology
• The extract exhibited good in vitro antiplasmodial and in vivo antimalarial activities. • The extract corrected blood disturbances and liver and kidney function failure and improved architecture of organs. • Compounds identified from the extract showed high binding affinity to some specific Plasmodium protein targets and presented favourable bioavailability. The use of plant-based remedies represents a complementary approach to combat malaria, particularly in countering the emergence of parasite resistance to conventional drugs. Eugenia ancorifera , a plant native to Cameroon, has a history of traditional application in managing malaria. This research sought to evaluate the antimalarial potential of a hydroethanolic extract from its leaves, employing in vitro, in vivo and in silico methods to analyze its efficacy and the compounds it contains. Antiplasmodial effects were tested in vitro against Plasmodium falciparum strains using a SYBR-green fluorescence-based method. The in vivo test was performed on Wistar rats infected with Plasmodium berghei ANKA. Chemical characterization via High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-DAD-ESI-QTOF-MS/MS) identified constituent compounds, which were subsequently subjected to computational analysis. This in silico study predicted their pharmacokinetic profiles and binding affinities to specific parasitic targets, including purine nucleoside phosphorylase (2BSX), Plasmodium falciparum actin I (4CBU), type II NADH dehydrogenase (5JWA), 6-phosphogluconate dehydrogenase (6FQY), and Plasmodium falciparum apicoplast DNA polymerase (7SXL). A cytotoxicity test and acute toxicity assay were also conducted. The extract showed good in vitro inhibition, with half-maximal inhibitory concentration (IC 50 ) values of 7.40 μg/mL and 8.21 μg/mL, respectively, against P. falciparum drug sensitive (Pf3D7) and multidrug resistance (PfDd2) strains. In infected rats, the treatment significantly reduced ( P < 0.001) parasitemia in both suppressive and curative models. Administration of the extract, notably at a 50 mg/kg dose, led to marked recovery in blood parameters, biochemical indicators of hepatic and renal functions, oxidative balance, and the histological integrity of the liver, kidney, spleen, and intestine. Compounds such as quinic acid, gallic acid, myricitrin, ganoderic acid T-Q, ganolucidic acid B and euscaphic acid were identified in the extract. These compounds displayed good docking score to the selected parasitic enzymes and possessed favorable drug-likeness properties, suggesting a role in the observed antimalarial activity. Furthermore, no toxic effect was observed at the dose up to 5000 mg/kg in rats. The results validate the traditional use of E. ancorifera to treat malaria. Its promising antimalarial properties warrants further investigation for potential development into a new therapeutic agent against malaria.