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The whole extract of <jats:italic>Maytenus senegalensis<\/jats:italic> has been scientifically investigated for potential biological activities both in vitro and in vivo, demonstrating strong antimalarial activity. However, there is a lack of data on the electrocardiographic effects of <jats:italic>M. senegalensis<\/jats:italic> in humans, which is a crucial aspect in the investigation of malaria treatment. Assessing the electrocardiographic effects of <jats:italic>M. senegalensis<\/jats:italic> is essential, as many anti-malarial drugs can inadvertently prolong the QT interval on electrocardiograms. Therefore, the study's objective was to evaluate the electrocardiographic effects of <jats:italic>M. senegalensis<\/jats:italic> in healthy adult volunteers.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This study is a secondary analysis of an open-label single-arm dose escalation. Twelve healthy eligible Tanzanian males, aged 18 to 45, were enrolled in four study dose groups. A single 12-lead electrocardiogram (ECG) was performed at baseline and on days 3, 7, 14, 28, and 56.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>No QTcF adverse events occurred with any drug dose. Only one volunteer who received the highest dose (800\u00a0mg) of <jats:italic>M. senegalensis<\/jats:italic> experienced a moderate transient change (\u25b3QTcF\u2009&gt;\u200930\u00a0ms; specifically, the value was 37\u00a0ms) from baseline on day 28. There was no difference in maximum QTcF and maximum \u25b3QTcF between volunteers in all four study dose groups.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>A four-day regimen of 800\u00a0mg every 8\u00a0h of <jats:italic>M. senegalensis<\/jats:italic> did not impact the electrocardiographic parameters in healthy volunteers. This study suggests that <jats:italic>M. senegalensis<\/jats:italic> could be a valuable addition to malaria treatment, providing a safer alternative and potentially aiding in the battle against artemisinin-resistant malaria. The results of this study support both the traditional use and the modern therapeutic potential of <jats:italic>M. senegalensis<\/jats:italic>. They also set the stage for future research involving larger and more diverse populations to explore the safety profile of <jats:italic>M. senegalensis<\/jats:italic> in different demographic groups. This is especially important considering the potential use of <jats:italic>M. senegalensis<\/jats:italic> as a therapeutic agent and its widespread utilization as traditional medicine.<\/jats:p>\n                <jats:p><jats:italic>Trial registration<\/jats:italic> ClinicalTrials.gov, NCT04944966. 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IHI\/IRB\/AMM\/No: 13-2020), the Senate Research and Publications Committee of the Muhimbili University of Health and Allied Sciences (Ref. No. DA.282\/298\/01.C\/30), and the National Institute for Medical Research, Tanzania (NIMR\/HQ\/R.8a\/Vol. IX\/3639). The trial was also approved by the Tanzania Medicines and Medical Devices Authority (TMDA) (Ref. No. TMDA0020\/CTR\/0013\/03).In this study, written informed consent was obtained from all volunteers. They were given sufficient time to read the trial information sheet before signing the consent form. 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