The in vivo trypanocidal effect of the diterpene 5-epi-icetexone obtained from Salvia gilliesii

Abstract

The search for new compounds with trypanocidal activity is crucial for the treatment of Chagas' disease. Previous in vitro studies have shown that the diterpene 5-epi-icetexone (ICTX) is active against Trypanosoma cruzi. The aim of this work was to evaluate the effect of ICTX on the parasites in infected mice, in an experimental model that mimics the acute phase of the disease. Swiss albino mice were infected with T. cruzi and treated daily with 10mg/kg/day ICTX (i.p.). Infected mice and mice injected with either saline or the vehicle DMSO were used as controls. Animals' survival and parasitemia were monitored once a week and histological studies were made at necropsy by the 5th week after infection. It was observed that the administration of ICTX increased the survival of mice infected, and induced a significant decrease in the parasitemia, as compared to controls. A similar protective effect was observed when animals were treated orally with benznidazole (BZN, used as a control of antiparasitic effect). By the 5th week post-infection, the presence of amastigote nests was observed within the fibers of the cardiac and skeletal muscle in controls, but not in animals treated with either ICTX or BZN. In addition, inflammatory infiltrates were observed in the tissues of controls, but not in animals treated with the drugs. We conclude that ICTX has an antiparasitic effect against T. cruzi, thus constituting an interesting option for the treatment of Chagas' disease, alone or combined with other drugs.

Diterpenes as lead molecules against neglected tropical diseases

“…However, serratol (Schmidt et al ., ), hypoestenonols A/B (Al Musayeib et al ., ), and diterpenes from some Vietnamese corals (Thao et al ., ) were found to act against Trypanosoma brucei ). Additionally, a number of other diterpenes (Alves et al ., ; Freiburghaus et al ., ; Batista et al ., ; Scio et al ., ; Uchiyama et al , ; Torres‐Mendoza et al , ; Rubio et al ., ; González et al ., ; Sanchez et al ., ; Ambrósio et al ., ; Sartorelli et al ., ; Izumi et al ., ; Ramírez‐Macías et al ., ; Lozano et al ., ; Siless et al ., ; Bou et al ., ; Olmo et al ., ; Lozano et al ., ; Lozano et al ., ) are also reported to act against T. cruzi.…”

Antiparasitic Activity of Diterpenoids Against Trypanosoma cruzi

“…Other diterpenes, such as geranylgeraniol from Pterodon pubescens (Fabaceae), 6β-hydroxy-18-acetoxycassan-13,15-diene from Myrospermum frutescens (Fabaceae), cyclocoulterone and komaroviquinone from Dracocephalum komarovi (Lamiaceae), and 5epi-icetexone from Salvia gilliessi (Lamiaceae), have previously demonstrated potent activity on epimastigote forms of T. cruzi [22][23][24][25][26]. Abietane diterpenoids taxodione, ferruginol, 6-hydroxysalvinolone, and uncinatone from the roots of Clerodendrum eriophyllum (Verbenaceae) have shown significant activity against promastigote forms of the trypanosomatid Leishmania donovani, with IC 50 values of 0.1, 4.0, 3.2, and 0.2 µg/mL, respectively [27].…”

Contribution of Microscopy for Understanding the Mechanism of Action Against Trypanosomatids

“…In animal models, it has been demonstrated that ICTX can protect mice from T. cruzi, at least during the early stages of infection (Fig. 11.10) (Lozano et al 2016).…”