Unveiling the Antimalarial Potential of Leaf Extracts of Mussaenda erythrophylla Schum. & Thonn. and Mussaenda philippica Dona Luz x M. flava in Mice

Malaria remains a major global public health concern, particularly in tropical regions. The increasing resistance to the current antimalarial drugs highlights the urgent need for new and effective therapies. Medicinal plants offer a promising source of novel and affordable antimalarial compounds for drug development. This study aimed to evaluate the antimalarial potential and acute oral toxicity of ethanolic leaf extract of Mussaenda erythrophylla Schum. & Thonn. (M. erythrophylla or Dona Trining) and Mussaenda philippica Dona Luz x M. flava (M. philippica or Dona Marmalade). Male Institute of Cancer Research (ICR) mice were treated with crude extracts at doses of 200, 400, and 600 mg/kg body weight, and the antimalarial activity was assessed using a 4-day suppressive test against Plasmodium berghei ANKA strain. The ethanolic leaf extract of M. erythrophylla exhibited a parasite suppression of 12.31%, 39.59%, and 59.76% at 200, 400, and 600 mg/kg, respectively. Similarly, M. philippica leaf extract suppressed parasitemia by 36.18%, 36.40%, and 71.02% at the corresponding doses. All extract concentrations, except for the 200 mg/kg dose of M. erythrophylla, exhibited higher effects compared to the negative controls (p < 0.05). At a dose of 2000 mg/kg, acute oral toxicity testing revealed no changes in ALT, ALP, BUN, or creatinine levels compared to controls, although AST levels were elevated. This increase was considered a possible mild adaptive response rather than a sign of overt toxicity. No alterations were observed in the physical activity or behavior of the mice, including piloerection, lacrimation, feeding activity, abnormal secretions, sleep patterns, or unusual excitement. Additionally, neither crude extract induced histological alterations in liver or kidney tissues. In conclusion, ethanolic leaf extracts of M. erythrophylla and M. philippica demonstrated promising antimalarial activity and were deemed safe at the tested doses, demonstrating safety up to 2000 mg/kg with only mild AST elevation and no observable histopathological damage. Extending the previous in vitro results of potent antimalarial activity and low cytotoxicity, our in vivo findings strongly support the efficacy and safety of these extracts. Further research is recommended to isolate and identify the active compounds responsible for the observed effects.