Natural phytochemicals reverting M2 to M1 macrophages: A novel alternative leishmaniasis therapy

Leishmaniasis is a tropical parasitic disease caused by the protozoan Leishmania which remains a significant global health concern with diverse clinical manifestations. Transmitted through the bite of an infected sandfly, its progression depends on the interplay between the host immune response and the parasite. The disease outcome is linked to macrophage polarisation into M1 and M2 phenotypes. M1 macrophages are pro-inflammatory and promote parasite clearance, while M2 macrophages support tissue repair and parasite survival by facilitating promastigote entry and intracellular amastigote proliferation.

The review focuses on discovering novel phytochemicals that exploit the immunomodulatory properties of macrophages, which can serve as an alternative antileishmanial treatments due to their diverse chemical structures and ability to modulate immune responses. It examines the immunomodulatory effects of phytochemicals that directly or indirectly promote antileishmanial activity by influencing macrophage polarisation and cytokine secretion. They can induce M1 macrophage polarisation to directly combat leishmaniasis or suppress M2 macrophages, thereby exerting indirect antileishmanial activity by influencing the release of M1-and M2-related cytokines.

Phytochemicals demonstrate antileishmanial effects through ROS production, M1 activation, and cytokine modulation. They regulate M1/M2-related cytokines and macrophage activity, influencing immune responses. Although their effects may be non-specific, targeted delivery strategies could overcome current therapeutic limitations, positioning phytochemicals as promising candidates for leishmaniasis treatment to counter the limitations of current medications.