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BACKGROUND The anti-inflammatory and cardioprotective properties of curcumin (Cur), a natural polyphenolic flavonoid isolated from the rhizomes of  Curcuma longa , are increasingly considered to have beneficial effects on the progression of Chagas heart disease, caused by the protozoan parasite  Trypanosoma cruzi .   OBJECTIVE   To evaluate the effects of oral therapy with Cur on  T. cruzi -mediated cardiovasculopathy in acutely infected mice and analyse the  in vitro  response of parasite-infected human microvascular endothelial cells treated with this phytochemical.    METHODS   Inflammation of heart vessels from Cur-treated and untreated infected mice were analysed by histology, with benznidazole (Bz) as the reference compound. Parasitaemia was monitored by the direct method. Capillary permeability was visualised by Evans-blue assay. Myocardial  ET-1 ,  IL-6 , and  TNF-α  mRNA expressions were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Microvascular endothelial HMEC-1 cells were infected  in vitro  with or without addition of Cur or Bz. Induction of the Ca 2+ /NFAT pathway was assessed by fluorometry, immunoblotting, and reporter assay.    FINDINGS   Oral Cur therapy of recently infected mice reduced inflammatory cell infiltration of myocardial arteries without lowering parasite levels. Compared to that of the phosphate-buffered saline-receiving group, hearts from Cur-treated mice showed significantly decreased vessel inflammation scores (p < 0.001), vascular permeabilities (p < 0.001), and levels of  IL-6 / TNF-α  (p < 0.01) and  ET-1  (p < 0.05) mRNA. Moreover, Cur significantly (p < 0.05 for transcript; p < 0.01 for peptide) downregulated ET-1 secretion from infected HMEC-1 cells. Remarkably, Cur addition significantly (p < 0.05 at 27.0 μM) interfered with  T. cruzi -dependent activation of the Ca 2+ /NFATc1 signalling pathway that promotes generation of inflammatory agents in HMEC-1 cells.    CONCLUSIONS   Oral treatment with Cur dampens cardiovasculopathy in acute Chagas mice. Cur impairs the Ca 2+ /NFATc1-regulated release of ET-1 from  T. cruzi -infected vascular endothelium. These findings identify new perspectives for exploring the potential of Cur-based interventions to ameliorate Chagas heart disease.

memórias do instituto oswaldo cruz

Curcumin exerts anti-inflammatory and vasoprotective effects through amelioration of NFAT-dependent endothelin-1 production in mice with acute Chagas cardiomyopathy