Plant-derived immunomodulatory compounds in experimental leishmaniasis: a systematic review

Abstract

Abstract Leishmaniasis is a neglected tropical disease that remains a major public health problem in many endemic regions. Current treatments are limited by toxicity, high cost, and emerging drug resistance. Plant-derived compounds have been investigated as potential therapeutic alternatives due to their antiparasitic and immunomodulatory properties. This systematic review aimed to evaluate the therapeutic potential and immunomodulatory effects of plant-derived compounds in experimental models of leishmaniasis. A systematic search was conducted in PubMed, Scopus, and Web of Science databases for studies published between January 2014 and December 2024. The search strategy included terms related to Leishmania, medicinal plants, natural products, and experimental models. Eligible studies were in vivo experimental investigations evaluating plant extracts, fractions, or isolated compounds in animal models of leishmaniasis. Study selection followed the PRISMA 2020 guidelines. Data were extracted regarding experimental models, phytochemical composition, antiparasitic outcomes, and immunological responses. Ten studies met the inclusion criteria. Most studies were conducted in BALB/c mice infected with Leishmania donovani or Leishmania (Leishmania) amazonensis. Plant-derived treatments included crude extracts, purified fractions, and isolated compounds such as lupeol and plant-derived protease inhibitors. The evaluated treatments demonstrated significant reductions in parasite load in liver, spleen, or lesion sites. Immunological analyses consistently showed a shift toward a protective Th1-type immune response, characterized by increased production of IFN-γ, IL-12, nitric oxide (NO), and reactive oxygen species (ROS), along with decreased levels of IL-10 and TGF-β. Several studies also reported improvements in histopathological parameters and low toxicity. Plant-derived compounds demonstrate promising antiparasitic and immunomodulatory effects in experimental models of leishmaniasis. These findings support the potential of natural products as alternative or complementary therapeutic strategies for leishmaniasis. However, further standardized experimental studies and clinical investigations are necessary to validate their safety and efficacy.