Antimalarial potential and toxicity assessment of a polyherbal combination of Azadirachta indica A. Juss., Cymbopogon citratus (DC.) Stapf., and Psidium guajava L. in rodents

Ethnopharmacological relevance: Malaria continues to be a major public health burden in sub-Saharan Africa, particularly due to the emergence of drug-resistant Plasmodium strains and limited access to effective therapies. In African traditional medicine, Azadirachta indica A. Juss., Cymbopogon citratus (DC.) Stapf., and Psidium guajava L. are commonly used for managing malaria. However, their combined efficacy and safety as a standardized polyherbal preparation remain underexplored. Aim of the study: This study evaluated the antimalarial efficacy and safety profile of a polyherbal formulation (Phymepalu Extract - PPE) prepared from A. indica, C. citratus, and P. guajava in rodent models. Materials and methods: The antimalarial activity of the PPE extract was assessed using a 4-day curative test in Plasmodium berghei-infected mice at doses of 30, 60, 90, and 120 mg/kg body weight. Hydroxychloroquine (25 mg/kg) was used as a positive control. Acute oral toxicity was evaluated in rats according to OECD Guideline 423, while subacute (28-day) and subchronic (90-day) toxicity studies followed OECD Guidelines 407 and 408, respectively. Toxicological evaluations included clinical signs, body weight, haematological and biochemical parameters, and histopathological analysis of key organs. Results: The PPE extract exhibited dose-dependent antimalarial activity, with 90 mg/kg producing the highest parasitaemia inhibition (76 %), compared to 92 % with hydroxychloroquine. No mortality or signs of acute toxicity were observed at 5000 mg/kg. Repeated administration over 28 and 90 days did not result in significant changes in clinical, haematological, biochemical, or histopathological indices, indicating good tolerability. Conclusion: The PPE extract demonstrated significant antimalarial activity and an excellent safety profile in preclinical models, supporting its traditional use. These findings justify further investigations toward its development as a safe and effective phytotherapeutic agent for malaria.