Morinda citrifolia Linn. Reduces Parasite Load and Modulates Cytokines and Extracellular Matrix Proteins in C57BL/6 Mice Infected with Leishmania (Leishmania) amazonensis

The absence of an effective vaccine and the debilitating chemotherapy for Leishmaniasis demonstrate the need for developing alternative treatments. Several studies conducted with Morinda citrifolia have shown various biological activities, including antileishmanial activity, however its mechanisms of action are unknown. This study aimed to analyze the in vivo activity of M. citrifolia fruit juice (Noni) against Leishmania (Leishmania) amazonensis in C57BL/6 mice. M. citrifolia fruit juice from the Brazilian Amazon has shown the same constitution of other juices produced around the world and liquid chromatography–mass spectrometry analysis identified five compounds: deacetylasperulosidic acid, asperulosidic acid, rutin, nonioside B and nonioside C. Daily intragastric treatment with Noni was carried out after 55 days of L. (L.) amazonensis infection in C57BL/6 mice. Parasitic loads, cytokine and extracellular protein matrix expressions of the lesion site were analyzed by qPCR. Histopathology of the lesion site, lymph nodes and liver were performed to evaluate the inflammatory processes. Cytokines and biochemical parameters of toxicity from sera were also evaluated. The Noni treatment at 500 mg.kg-1.day-1 for 60 days decreased the lesion size and parasitic load in the footpad infected with L. (L.) amazonensis. The site of infection also showed decreased inflammatory infiltrates and decreased cytokine expressions for IL-12, TNF-α, TGF-β and IL-10. On the other hand, Noni treatment enhanced the extracellular matrix protein expressions of collagen IV, fibronectin and laminin in the infected footpad as well collagen I and II, fibronectin and laminin in the mock-infected footpads. No toxicity was observed at the end of treatment. These data show the efficacy of Noni treatment.
Author Summary Leishmaniasis is a complex of diseases caused by parasites of the Leishmania genus, which affects thousands of people around the world. The parasite lives within the cells and the disease manifests itself in different ways, one of them is wound-like lesions on the skin that do not heal. The treatment, with a medicament discovered in 1912, causes several side effects, its intramuscular administration is painful and it is given daily over a long period of time. These characteristics show the need for new alternatives for leishmaniasis treatment justifying works like this. The Morinda citrifolia is a plant native to the Polynesian islands and has a fruit commonly known as Noni. Noni has been analyzed for various targets such as anticancer, anti-inflammatory and antimicrobial effects; however, the antileishmanial has not yet been fully evaluated. This work proves that Noni treatment can promote a fast clinical cure in mice with leishmaniasis by decreasing parasite number, acting on the immune system and repairing skin components.