Reduction of parasitism tissue by treatment of mice chronically infected with Trypanosoma cruzi with lignano lactones

Abstract

The reduction of parasitism tissue upon treatment with two lignano lactones, namely (-)- cubebin (CUB) and (-)-hinokinin (HNK), was evaluated in the chronic phase of Chagas' disease by quantifying the enzyme beta-galactosidase expressed by the CL B5 clone strain of Trypanosoma cruzi. Tissue karyometry was also performed. Treatment with the assessed lignans led to a larger reduction in parasitism tissue in all evaluated organs, compared with benznidazole (BZN). Oral treatment with CUB or HNK was more effective. Karyometry results demonstrated that the infected control animals had increased nuclear area compared with uninfected controls, indicating cellular hypertrophy. Results also revealed that use of CUB or HNK was able to significantly prevent this increase, and a slight decrease in the nuclear area was observed, compared with mice treated with BZN. Taken together, these data demonstrate that CUB and HNK could be considered as potential compounds for the development of new drugs for treatment of Chagas' disease.

In vitro and in vivo anthelmintic activity of (−)-6,6′-dinitrohinokinin against schistosomula and juvenile and adult worms of Schistosoma mansoni

“…Among the several classes of plant-derived secondary metabolites, lignans constitute a class that displays a wide spectrum of biological activities (Apears et al, 2003), including their action against parasites that cause neglected tropical diseases such as trypanosomiasis (Saraiva et al, 2007;Esperandim et al, 2010) and leishmaniasis (Royo et al, 2003). In a previous work, our group found that (-)-cubebin from Piper cubeba (used in the semi-synthesis of DNK in the present work) did not kill Schistosoma mansoni but minimized the movement that occurred at concentrations of 100 and 200…”

“…Over the last few years, our team has evaluated the biological activity of extracts and compounds isolated from Piper cubeba against neglected parasitic diseases (Saraiva et al, 2007;Esperandim et al, 2010;Magalhães et al, 2012). The compound 3,4-bis ((6-nitrobenzo[d] [1,3]dioxol-5-yl)methyl)-dihydrofuran-2(3H)-one) ((-)-6,6´-dinitrohinokinin, DNK) is a dibenzylbutyrolactone lignan.…”

“…The compound 3,4-bis ((6-nitrobenzo[d] [1,3]dioxol-5-yl)methyl)-dihydrofuran-2(3H)-one) ((-)-6,6´-dinitrohinokinin, DNK) is a dibenzylbutyrolactone lignan. This class of lignans consists of compounds that display a broad range of biological activities with therapeutic potential (Saraiva et al, 2007;Esperandim et al, 2010).…”

Synergistic Effect of Lupenone and Caryophyllene Oxide againstTrypanosoma cruzi

“…The animals were infected with 100 trypomastigotes through intraperitoneal injection; inoculation conditions were selected based to the reported in previous studies in mice infected with T. cruzi in chronic phase [18, 19]. Mice were divided into five groups: negative control (CN): infected animals treated with PBS; positive control (CP): infected animals treated with allopurinol (8.5  μ g/g); hexane fraction (FHex): animals treated with the hexane fraction from the leaf crude extract of S. yucatanensis (41.6 mg·kg −1 ·day −1 ); dose 1 (D1): infected mice treated with a 20.8 mg·kg −1 ·day −1 1 : 4 mixture of lupenone and caryophyllene oxide; dose 2 (D2): infected mice treated with a 41.6 mg·kg −1 ·day −1 1 : 4 mixture of lupenone and caryophyllene oxide.…”

Advances in Chagas disease drug development: 2009–2010

“…Previously discovered lignano lactones from the plant Piper cubeba [47] were shown to have in vivo activity in mice infected with T. cruzi (CL strain) [48]. Specifically, tissue parasites were reduced as low as 20% of control levels in mice given cubebin ( #8, Fig.…”