Anti-Trypanosoma cruzi activity of green tea (Camellia sinensis) catechins.
The trypanocidal action of green tea catechins against two different developmental stages of Trypanosoma cruzi is reported for the first time. This activity was assayed with the nonproliferative bloodstream trypomastigote and with the intracellular replicative amastigote parasite forms. An ethyl acetate fraction from Camellia sinensis green tea leaves, which contains most of the polyphenolic compounds and the maximal trypanocidal activity, was obtained by fractionation of the aqueous extract with organic solvents. The active compounds present in this extract were further purified by LH-20 column chromatography and were identified by high-performance liquid chromatography analysis with a photo diode array detector and gas chromatography coupled to mass spectroscopy. The following flavan-3-ols derivatives, known as catechins, were identified: catechin, epicatechin, gallocatechin, epigallocatechin, catechin gallate, epicatechin gallate, gallocatechin gallate, and epigallocatechin gallate. The purified compounds lysed more than 50% of the parasites present in the blood of infected BALB/c mice at concentrations as low as 0.12 to 85 pM. The most active compounds were gallocatechin gallate and epigallocatechin gallate, with minimal bactericidal concentrations that inhibited 50% of isolates tested of 0.12 and 0.53 pM, respectively. The number of amastigotes in infected Vero cells decreased by 50% in the presence of each of these compounds at 100 nM. The effects of the catechins on the recombinant T. cruzi arginine kinase, a key enzyme in the energy metabolism of the parasite, were assayed. The activity of this enzyme was inhibited by about 50% by nanomolar concentrations of catechin gallate or gallocatechin gallate, whereas the other members of the group were less effective. On the basis of these results, we suggest that these compounds could be used to sterilize blood and, eventually, as therapeutic agents for Chagas' disease.
Paveto
Cristina
C
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular y Facultad de Ciencias Exactas y Naturales (CONICET-UBA), 1428 Buenos Aires, Argentina. cpaveto@dna.uba.ar
Güida
María C
MC
Esteva
Mónica I
MI
Martino
Virginia
V
Coussio
Jorge
J
Flawiá
Mirtha M
MM
Torres
Héctor N
HN
D000818:Animals; D001122:Arginine Kinase / Q000378:metabolism; D028244:Camellia / Q000737:chemistry*; D002392:Catechin / Q000494:pharmacology* / Q000627:therapeutic use; D014355:Chagas Disease / Q000097:blood / Q000188:drug therapy / Q000469:parasitology; D002522:Chlorocebus aethiops; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D007202:Indicators and Reagents; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D014344:Trypanocidal Agents; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000201:enzymology; D014709:Vero Cells
D007202:Indicators and Reagents; D010936:Plant Extracts; D014344:Trypanocidal Agents; D002392:Catechin; D001122:Arginine Kinase