Plant-based therapeutics for leishmaniasis: A systematic review emphasizing human studies and clinical trial evidence

Leishmaniasis is a parasitic disease caused by Leishmania species and transmitted through sand fly bites, affecting some of the most vulnerable populations globally. Current treatments are limited by high toxicity, poor tolerability, and resistance. Plant-based therapies offer a promising alternative, but human evidence has not been comprehensively reviewed. This review summarizes current evidence on the efficacy and safety of plant-based treatments for leishmaniasis in humans.

We conducted a systematic review including studies that evaluated the efficacy and safety of plant-based treatments for leishmaniasis in humans. This review was registered with PROSPERO (ID: CRD42024567764). We searched PubMed, Scopus, and Web of Science from inception to May 28, 2024. Risk of bias was assessed using the Cochrane RoB 2 tool. We summarized the main study results qualitatively and quantitatively (where possible) by estimating risk ratios with 95% confidence intervals for treatment outcomes using the meta package in R. Ten studies met the inclusion criteria, nine from Iran and one from Sudan, all focused on cutaneous leishmaniasis (CL). Most used topical creams derived from medicinal plants, either alone or with conventional treatments. In studies combining herbal and standard treatments, four of six studies showed better outcomes in the intervention group. In studies using only the plant-based treatments compared to a standard treatment group, two of four showed better outcomes in the intervention group. Quantitative analysis of eight studies indicated significant healing improvements in the intervention group in three studies, specifically those using Juniperus excelsa, Nigella sativa, and poly-herbal formulations consisting of the pure extract mixture of Althaea (A.) rosa, A. officinalis, and members of the families Leguminosae, Faliaceae, Malvaceae, and Lythraceae (named Z-HE). Mild side effects such as itching and burning were reported with some herbal treatments, while conventional therapies caused more severe reactions in some cases. The risk of bias was mostly high in the studies.

This review highlights the potential of certain plant-based compounds as adjunct or alternative therapies for CL. Despite promising results with Plantago ovata, Juniperus excelsa, and Z-HE poly-herbal extracts, current evidence is limited by methodological weaknesses. Larger, rigorously designed trials with broader representation are needed to confirm efficacy and safety and support policy integration in endemic regions.