Theracurmin Modulates Cardiac Inflammation in Experimental Model of Trypanosoma cruzi Infection

Abstract

Theracurmin is a nanoparticle formulation derived from curcumin, a bioactive compound known for its antioxidant and anti-inflammatory properties. Trypanosoma cruzi, the etiological agent of Chagas disease, triggers an intense inflammatory response in mammals and also causes severe tissue damage. To evaluate the immunomodulatory and antiparasitic effects of Theracurmin, Swiss mice were experimentally infected with 103 trypomastigote forms of the Colombian strain of T. cruzi and submitted to daily therapy with 30 mg/kg of Theracurmin. In addition, daily benznidazole therapy (100 mg/kg) was performed as a positive control. We evaluated the systemic and tissue parasitism, the survival and the body mass rate, the release of inflammatory mediators (TNF, IL-6, IL-15, CCL2 and creatine kinase) and the tissue inflammation at day 30 post-infection. Theracurmin therapy reduced the parasitemia curve without altering the animals’ survival rate, and it protected mice from losing body mass. Theracurmin also reduced CCL2 in cardiac tissue, IL-15 in cardiac and skeletal tissue, and plasma CK. Even without effects on TNF and IL-6 production and tissue amastigote nests, Theracurmin reduced the leukocyte infiltrate in both evaluated tissues, even in the case of more effective results observed to the benznidazole treatment. Our data suggest Theracurmin has an immunomodulatory (CCL2, IL-15, CK and tissue leukocyte infiltration) and a trypanocidal effect (on circulating parasites) during experimental infection triggered by the Colombian strain of T. cruzi. Further investigations are necessary to comprehend the Theracurmin role performed in combination with benznidazole or other potential anti-T. cruzi chemical compounds.

Nanomedicines against Chagas disease: a critical review

“…A low BNZ dose (750 mg/kg TD) plus PLGA-CUR Nps, reduced cardiac hypertrophy and parasite load, chronic inflammation, fibrosis, and the levels and activities of cardiopathogenic biomarker enzymes and cytokines/chemokines (IL-1β, TNF-α, IL-6, and CCL5), matrix metalloproteinases (MMP-2 and MMP-9), and inducible enzymes (cyclooxygenase and nitric oxide synthase) implicated in leukocyte recruitment and cardiac remodelling [ 76 ]. More recently, Theracurmin ® (a natural product of Theravalues, Tokyo, Japan, that enhances the curcumin bioavailability 30-fold compared with curcumin powder [ 77 – 78 ]) showed immunomodulatory (reduced CCL2 in cardiac tissue, IL-15 in cardiac and skeletal tissue, plasma creatine kinase, and tissue leukocyte infiltration) and trypanocidal effects (reduction of parasitemia) in an acute murine model [ 79 ]. A complementary use of Theracurmin ® with BNZ therapy is suggested.…”

Tropical Infectious Diseases of Global Significance: Insights and Perspectives

“…Louise and colleagues [28] demonstrated that theracurmin, a nanoparticle formulation derived from curcumin, was able to modulate cardiac inflammation in an in vivo murine model of Trypanosoma cruzi infection.…”