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

Abstract

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.

Morinda citrifolia noni water extract enhances innate and adaptive immune responses in healthy mice, ex vivo, and in vitro

“…At Week 0, the mRNA expression levels of IL‐1β, IL‐4, IL‐5, IL‐6, IL‐10, IL‐12, IL‐13, TNF‐α, IFN‐γ, COX‐2, or iNOS in mouse splenocytes were not altered by Mc‐eWE treatment (Figure a). However, at Week 4, Mc‐eWE significantly upregulated the mRNA expression of all of these genes (except for IL‐10) compared with normal controls, in a dose‐dependent manner (Figure b), unlike a report showing that treatment of noni fruit juice (500 mg/kg) for 60 days decreased the expression of inflammatory cytokines including IL‐12, TNF‐α, TGF‐β, and IL‐10 in Leishmania amazonensis ‐infected C57BL/6 mice (Almeida‐Souza, Cardoso Fde, et al, ). In accordance with this paper and our ex vivo mRNA expression results (Figure c), Mc‐eWE (400 mg/kg) significantly decreased the mRNA expression of IL‐10 compared with normal controls at Week 4 (Figure b).…”

“…Numerous papers have reported that extract or juice from fruit of noni is able to modulate functional role of immune cells such as NK cells, CD4 + T‐cells, CD8 + T‐cells, and B‐cells under disease conditions such as the tumor xenograft model, Leishmania amazonensis infection model, paw and ear edema model, picryl chloride‐induced contact dermatitis model, 12‐O‐tetradecanoylphorbol‐13‐acetate‐induced inflammation model, alcohol‐induced liver damage model, 12‐O‐tetradecanoylphorbol‐13‐acetate‐induced skin inflammation model, and DSS‐induced colitis model (Abu et al, ; Akihisa et al, ; Almeida‐Souza et al, ; Almeida‐Souza et al, ; Chang et al, ; Coutinho de Sousa et al, ; Li et al, ; Lim et al, ; Murata et al, ). In this study, however, we investigated the in vivo immunostimulatory activity of Mc‐eWE using mice under normal conditions, because we were curious on the immunoregulatory activity of noni fruit extract under healthy conditions.…”

The Influence of <i>Morinda citrifolia</i> (Noni) Fruit Juice on Collagen Deposition in the Skin: A Minireview

“…The procollagen properties of noni juice were also observed in C57/BL6 mice [13]. In these mice, ingestion of noni juice accelerated the healing of lesions from leishmaniasis.…”

Modulation of Cytokines and Extracellular Matrix Proteins Expression by Leishmania amazonensis in Susceptible and Resistant Mice

“…Although Th1 response is required to induce lesion healing in CL caused by L. major in humans and mice ( Kane and Mosser, 2001 ; Murray et al, 2002 ; Trinchieri et al, 2003 ), excessive proinflammatory cytokines, mainly IFN-γ and TNF-α, can contribute to development of mucosal leishmaniasis (LM) ( Follador et al, 2002 ) and to the tissue damage ( Ribeiro-de-Jesus et al, 1998 ) produced by cellular recruitment, as observed in infections caused by L. braziliensis ( Vargas-Inchaustegui et al, 2010 ) and L. amazonensis ( Carneiro et al, 2015 ). Studies conducted in mock-treated C57BL/6 L. amazonensis -infected mice showed an excessive secretion of pro-inflammatory cytokines in these animals, leading to uncontrolled tissue degradation and perpetuates the non-healing condition ( Almeida-Souza et al, 2016 ). However, the production of regulatory cytokines, mainly IL-10, is related to the control of exacerbated inflammatory response.…”