A review of efficacy and safety of Ugandan anti‑malarial plants with application of RITAM score

Abstract

Background: Malaria, a treatable disease mainly caused by Plasmodium falciparum has remained a health challenge in Africa, a continent that accounted for 96% of total global cases and deaths in 2021. Uganda, a malaria endemic country is experiencing malaria parasite resistance to some of the drugs used in the artemisinin-based combination therapy (ACT). In an effort to prioritize herbal medicines for new product development, this review synthesized the available safety and efficacy literature on the Ugandan anti-malarial plants to suggest most effective herbal plants. Methods: Literature was exhaustively searched using engines and databases, such as Google scholar, Pubmed, and Scopus-indexed journals during the period of June 2020–December 2021. In the first phase, information on ethnobotanical uses of anti-malarial plants in Uganda was gathered and synthetized to generate a list of plants, followed by data on anti-malarial efficacy (both in vitro and in vivo) on each listed plant. Minimum inhibitory concentrations (μg/ ml), and % parasite suppression for every plant were scored using The Research Initiative on Traditional and Antimalarial Methods: (RITAM) scoring system. The best twenty (20) plants were evaluated for acute safety ( LD50) data in rat model, plant parts used, ease of cultivation, presence of clinical studies and other relevant factors for suggesting the best three (3) plants for future anti-malarial product development. Results: Over one hundred twenty-six (126) plant species are used in Uganda for treatment of malaria in local communities. Out of these, about 33% (41) have been studied for efficacy and safety, with Artemisia annua and Vernonia amygdalina being the most extensively studied and among the best twenty (20) anti-malarial plants in Uganda. Both are limited by parasite recrudescence in clinical studies. Microglossa pyrifolia, a very potent plant (IC50 = 0.03 – 0.05 μg/ml has potential to penetrate the liver and could ameliorate the challenge of recrudescence if combined with A. annua and V. amygdalina in a polyherbal formulation. Conclusion: There are many plants with promising potential for malaria treatment in Uganda and a herbal combination of A. annua, V. amydalina and M. pyrifolia could offer the next herbal ACT if carefully studied and developed