Obakiroa, Samuel BakerNabitandikwa, CatherineKiyimba, KenedyOcan, MosesGavamukulya, YahayaAndima, MosesLukwago, Tonny WotoyitideMaseruka, RichardMercy, ChebijiraOpio, MosesHokello, JosephKibuule, DanNabatanzi, AliceOrenah, StephenWaako, PaulOwor, Oriko Richard2026-07-172026-07-172025Obakiro, S. B., Nabitanikwa, C., Kiyimba, K., Ocan, M., Gavamukulya, Y., Andima, M., Lukwago, T., Maseruka, R., Chebijira, M., Opio, M., Hokello, J. F., Kibuule, D., Nabatanzi, A., Orena, S., Waako, J. P., & Oriko, R. O. (2025). In vitro antiplasmodial activity, acute toxicity and phytochemical quantification of selected medicinal plants used in symptomatic management of malaria in eastern Uganda. SSRN. https://doi.org/10.2139/ssrn.5309695https://bdears.busitema.ac.ug/handle/123456789/8004Ethnopharmacological relevance: The emergence of artemisinin resistance alongside limited antimalarial access in Uganda has intensified the use of herbal medicines as complementary and alternative therapies. Whereas there is widespread indigenous use of Zanthoxylum chalybeum, Albizia coriaria, Entada abyssinica, Maytenus senegalensis, and Kigelia Africana in treatment of malaria, there was limited scientific evidence of efficacy and safety. Aim of the study: This study assessed the in vitro antiplasmodial activity, acute toxicity, and phytochemical composition of the five plants so as to identify alternative sources of antimalarial drugs. Materials and methods: Phytochemical screening and quantification was conducted on ethanolic extracts from dried samples using UV-Vis spectrophotometry. The acute toxicity testing was conducted in Wistar albino rats using limit dose test and the antiplasmodial efficacy evaluated using a 72-hour SYBR Green assay on Plasmodium falciparum laboratory and clinical isolates. Results: Alkaloids, flavonoids, tannins, and terpenoids were present in all the samples. Z. chalybeum was the most potent, with IC50 values as low as 0.90 and 1.54 µg/ml against both chloroquine-sensitive (3D7) and resistant (Dd2) strains respectively. Albizia coriaria and Entada abyssinica also displayed moderate activity, with IC50s ranging from 30.26 to 101.26 µg/ml. Acute toxicity studies indicated that most extracts were relatively safe in Wistar albino rats, except for A. coriaria and M. senegalensis, which were moderately toxic with median lethal less than 2000mg/kg. Conclusion: Z. chalybeum, A. coriaria and E. abyssinica are promising medicinal plants for developing novel and effective antimalarial drugs, especially against drug-resistant strains that warrant more phytochemical and pharmacological studies. Keywords: Medicinal plants, Malaria, Antiplasmodial activity, Phytochemicals, Drug resistanceenArticle