Study the Mechanism of Antileishmanial Action of Xanthium strumarium Against Amastigotes Stages in Leishmania major: A Metabolomics Approach

Abstract

Background: Leishmaniasis is among the most important neglected tropical infections, affecting millions of people worldwide. Since 1945, chemotherapy has been the primary treatment for leishmaniasis; however, lengthy and costly treatments associated with various side effects and strains resistant to the conventional therapy have dramatically reduced chemotherapy compounds’ efficacy. Objectives: The antileishmanial activity of the leaf extract of Xanthium strumarium (Asteraceae) was studied. New insights into its mechanism of action toward Leishmania major were provided through a metabolomics-based study. Methods: J774 macrophages were cultured, infected with stationary promastigotes, and treated with different leaf extract concentrations for three days. Antileishmanial activity was assayed by the MTT colorimetric method, and cell metabolites were extracted. 1HNMR spectroscopy was applied, and outliers were analyzed using multivariate statistical analysis. Results: Xanthium strumarium extract (0.15 µg/mL) showed the best activity against L. major amastigotes with the infection rate (IR) and multiplication index (MI) values of 51% and 57%, respectively. The action of X. strumarium extract on amastigotes was comparable with amphotericin B as the positive control (0.015 µg/mL). According to the obtained P-values, pentanoate and coenzyme A biosynthesis, pentose and glucuronate metabolism, valine, leucine and isoleucine biosynthesis, galactose metabolism, amino sugar and nucleotide sugar metabolism were the most important metabolic pathways affected by the plant extract in the amastigote stage of L. major. Conclusions: Our finding demonstrated that X. strumarium leaf extract could be used for discovering and producing novel leishmanicidal medicines. Moreover, the affected metabolic pathways observed in this study could be potential candidates for drug targeting against leishmaniasis.