TITLE:
Pharmacological and Toxicological Evaluation of Feretia apodanthera Delile (Rubiaceae) Leaf Extract: Effects on Physiological, Hematological and Biochemical Alterations in Plasmodium berghei-Infected Mice, with Acute and Subacute Toxicity Assessments
AUTHORS:
Saamou Isaac Boni, Nâg-Tero Roland Meda, Kouliga Benjamin Koama, Domonbabele François de Sales Hien, Mariam Youba, Zachari Kabre, Valentin Konsegre, Mohamed Haddad, Abdoulaye Diabate, Rakiswende Serge Yerbanga
KEYWORDS:
Feretia apodanthera, Plasmodium berghei, Malaria, Host Alterations, Acute Toxicity, Subacute Toxicity
JOURNAL NAME:
Open Journal of Applied Sciences,
Vol.16 No.5,
May
25,
2026
ABSTRACT: Malaria remains a major public health burden in sub-Saharan Africa, causing systemic complications beyond parasitemia. While many antimalarial plants have been investigated for their direct antiplasmodial activity, their potential to mitigate malaria-induced host alterations remains poorly explored. Among these, Feretia apodanthera Del. is widely used in traditional medicine for malaria and other infectious diseases. Although its antimalarial activity has been demonstrated in vitro and in vivo, its effects on malaria-associated physiological, hematological, and biochemical disturbances are unclear. Thus, this study aimed to evaluate the capacity of the methanolic leaf extract of F. apodanthera to modulate malaria-induced physiological, hematological, and biochemical disorders in Plasmodium berghei-infected NMRI mice, while assessing its safety profile. Both restorative and protective models were employed to investigate the extract’s impact on body weight, organ weights, and key biological parameters. In parallel, acute and subacute toxicity studies were conducted in accordance with OECD guidelines to determine its safety. The leaf extract reduced parasitemia by more than 50%. It had limited effects on body weight and did not significantly improve malaria-induced hematological alterations, but attenuated liver and kidney enlargement. Notably, it significantly reduced the elevation of liver enzymes (ALT and AST) and minimized organ alterations, particularly in the restorative model, indicating hepatoprotective and organ-protective effects. In the protective model, moderate biochemical effects were observed, although infection-induced alterations were not fully prevented. Acute toxicity evaluation revealed no mortality or clinical signs of toxicity at 2000 mg/kg, indicating a median lethal dose greater than 2000 mg/kg. Subacute administration over 28 days at all tested doses did not induce significant changes in body weight or organ weights and showed no evidence of dose-dependent toxicity, indicating the absence of systemic toxicity across the administered dose range. Furthermore, at the highest dose (2000 mg/kg), hematological, biochemical, and histopathological analyses revealed no signs of toxicity. Histopathological examination of the heart, lungs, liver, spleen, and kidneys confirmed the absence of tissue damage. Overall, the methanolic leaf extract of F. apodanthera is well tolerated and appears to limit malaria-induced physiological disturbances, particularly hepatic and renal alterations, while maintaining a favorable safety profile under both acute and repeated administration.