The effect of Bulgarian propolis against Trypanosoma cruzi and during its interaction with host cells

Abstract

Propolis has shown activity against pathogenic microorganisms that cause diseases in humans and animals. The ethanol (Et-Blg) and acetone (Ket-Blg) extracts from a Bulgarian propolis, with known chemical compositions, presented similar activity against tissue culture-derived amastigotes. The treatment of Trypanosoma cruzi-infected skeletal muscle cells with Et-Blg led to a decrease of infection and of the intracellular proliferation of amastigotes, while damage to the host cell was observed only at concentration 12.5 times higher than those affecting the parasite. Ultrastructural analysis of the effect of both extracts in epimastigotes revealed that the main targets were the mitochondrion and reservosomes. Et-Blg also affected the mitochondrion-kinetoplast complex in trypomastigotes, offering a potential target for chemotherapeutic agents.Key words: propolis -natural products -Trypanosoma cruzi -Chagas disease Chagas disease, caused by the trypanosomatid protozoan Trypanosoma cruzi, is endemic in Latin America. Initially restricted to natural ecotopes, with transmission among small autochthonous mammals by hematophagous Triatominae bugs, the occupation by humans of such ecotopes led to the establishment of the vectors in human dwellings, changing the characteristic of the disease from zoonotic to antropozoonotic. In humans, the acute phase results in 2-8% mortality, specially among children, while in the chronic phase most patients remain asymptomatic and about 30 to 40% of the cases develop symptoms of cardiac or digestive lesions. The World Health Organization estimates that about 18 million people are infected with T. cruzi (WHO 2002). The available drugs for the clinical treatment, the nitroderivatives benznidazole and nifurtimox, are unsatisfactory. They present variable healing effects during the acute phase according to the geographical region and require long term treatment, besides presenting frequent toxic side effects and limited efficacy in the chronic stage (reviewed in Coura & De Castro 2001).In this context, there is an intense search for new synthetic compounds and natural products for treatment of Chagas disease. Thus, our group has been engaged in experimental chemotherapy studies using propolis (Higashi & De Castro 1994, De Castro & Higashi 1995, Marcucci et al. 2001, Prytzyk et al. 2003, Paulino et al. 2003, Salomão et al. 2004). Propolis, a bee product collected from different plant exudates, is a complex mixture containing known bioactive constituents, such as flavonoids, phenolic acids and esters, terpenes, sesquiterpenes, aromatic aldehydes, and alcohols (Marcucci 1995). In temperate zones, bud exudates from poplar trees (Populus spp.) are the main source of flavonoid-rich propolis, which are rich in flavonoids (reviewed in Bankova et al. 2000).During the last decades, an increasing number of studies on the chemical composition, biological activity, and therapeutic uses of propolis has been published (reviewed in De Castro 2001). In recent studies with a Bulgarian propolis sample, we ...

Effects of Brazilian propolis on Leishmania amazonensis

“…Additional experiments with BRG and BRPG samples were abandoned because at concentrations higher than 25 µg/ml both extracts were toxic to macrophages. In fact some studies have demonstrated propolis toxicity for different cell types (Higashi & de Castro 1994, Chen et al 2001, Ferguson 2001, Dantas et al 2006, Tavares et al 2006. For example, damage to murine macrophages was observed after treatment with ethanolic extract of propolis at concentrations above 30 µg/ml (Higashi & de Castro 1994), and genotoxic effect of ethanolic extract of Brazilian propolis (100 µg/ml) was detected in Chinese hamster ovary cells (Tavares et al 2006).…”

“…It is widely used in products like "healthy foods" and "biocosmetics" (Marcucci & Bankova 1999). Many authors have reported the in vitro activities of propolis against different microorganisms, among them some important human pathogens, such as Staphylococcus aureus, Salmonella thyphimurium, Candida albicans, Trypanosoma cruzi, and Giardia duodenalis (Higashi & de Castro 1994, Marcucci et al 2001, Miorin et al 2003, Uzel et al 2005, Dantas et al 2006, Freitas et al 2006, Trusheva et al 2006. Brazilian propolis is the subject of an intensive study of chemists, biologists, and physicians all over the world due to specific tropical flora and their different chemical components (Marcucci & Bankova 1999, Marcucci et al 2001, Trusheva et al 2006.…”

Acanthoic acid and other constituents from the stem of Annona amazonica (Annonaceae)

“…Some previous studies have demonstrated the therapeutic potential of compounds derived from natural sources. 16,[48][49] Several synthetic compounds have also shown trypanocidal activity. 50,51 Acanthoic acid (1) at 3 µmol L -1 (the lowest concentration tested) displayed a growth inhibition of parasites of 13.6%, while at the highest concentration (331 µmol L -1 ), over 90% of the cells were affected.…”

Bulgarian Bee Products and their Health Promoting Potential

“…its antimicrobial properties are the most often studied and there are numerous articles proving the action of Bulgarian bee glue against bacteria (6,17,42), incl. Helicobacter pylory (10,11) and Salmonella (36); anti-influenza virus activity (29,43), antiparasitic activity against Tripanozoma cruzii (12,40) and Leishmania (28). the immunomodulatory activity of Bulgarian propolis has also been reported (13,14,15).…”