In vitro cytocidal effects of the essential oil from Croton cajucara (red sacaca) and its major constituent 7- hydroxycalamenene against Leishmania chagasi

Abstract

BackgroundVisceral leishmaniasis is the most serious form of leishmaniasis and can be lethal if left untreated. Currently available treatments for these parasitic diseases are frequently associated to severe side effects. The leaves of Croton cajucara are used as an infusion in popular medicine to combat several diseases. Previous studies have demonstrated that the linalool-rich essential oil from C. cajucara (white sacaca) is extremely efficient against the tegumentary specie Leishmania amazonensis. In this study, we investigated the effects of the 7-hydroxycalamenene-rich essential oil from the leaves of C. cajucara (red sacaca) against Leishmania chagasi, as well as on the interaction of these parasites with host cells.MethodsPromastigotes were treated with different concentrations of the essential oil for determination of its minimum inhibitory concentration (MIC). In addition, the effects of the essential oil on parasite ultrastructure were analyzed by transmission electron microscopy. To evaluate its efficacy against infected cells, mouse peritoneal macrophages infected with L. chagasi promastigotes were treated with the inhibitory and sub-inhibitory concentrations of the essential oil.ResultsThe minimum inhibitory concentrations of the essential oil and its purified component 7-hydroxycalamenene against L. chagasi were 250 and 15.6 μg/mL, respectively. Transmission electron microscopy analysis revealed important nuclear and kinetoplastic alterations in L. chagasi promastigotes. Pre-treatment of macrophages and parasites with the essential oil reduced parasite/macrophage interaction by 52.8%, while it increased the production of nitric oxide by L. chagasi-infected macrophages by 80%.ConclusionThese results indicate that the 7-hydroxycalamenene-rich essential oil from C. cajucara is a promising source of leishmanicidal compounds.

Arrabidaea chicaHexanic Extract Induces Mitochondrion Damage and Peptidase Inhibition onLeishmaniaspp.

“…In addition, an intense exocytic process of cytoplasmic content into the flagellar pocket was noted. Mitochondrion seems to be a common target for several natural products, crude extracts, or isolated compounds, as has been reported by several researchers [10, 22–24]. The mode of action of most natural products that cause mitochondrial damage and parasite death has been attributed mainly to sterol biosynthesis inhibition and mitochondrial membrane potential dysfunction [25–27].…”

In vitro activity of ‘Mexican Arnica’ Heterotheca inuloides Cass natural products and some derivatives against Giardia intestinalis

“…Natural products isolated from H. inuloides and semisynthetic derivatives that were assayed for activity against Giardia intestinalis. Although several compounds isolated from H. inuloides have antiinflammatory activity (Delgado et al 2001) and it has been found that the 7-hydroxycalamenene shows activity against Leishmania chagasi promastigotes with a minimum inhibitory concentration of 15·6 μg mL − 1 (Rodrigues et al 2013), this is the first report that 1 and 14 can act as antigiardial agents. The failure rates reflect the need for more alternatives for treating giardiasis.…”

Chemical Characterization, Antileishmanial Activity, and Cytotoxicity Effects of the Essential Oil from Leaves of Pluchea carolinensis (Jacq.) G. Don. (Asteraceae)

“…Our in vitro results in amastigotes also revealed better activity than other EOs obtained from Cuban plants, including Artemisia absinthium L. (Asteraceae), IC 50 = 13.4 μg/mL (Monzote et al ., ), and Bixa orellana L. (Bixaceae) IC 50 = 8.5 μg/mL (Monzote et al ., 2014 b). In addition, a lower IC 50 value was also obtained than some EOs reported in the literature: Croton cajucara Benth (Euphorbiaceae), IC 50 = 66.7 μg/mL (Rodrigues et al ., ); Lippia sidoides Cham (Verbenaceae), IC 50 = 44 μg/mL (de Medeiros et al ., ); Vanillosmopsis arborea Baker (Asteraceae), IC 50 = 12.6 μg/mL (Colares et al ., ); Aristolochia cymbifera Mart (Aristolochiaceae); Lippia alba (Mill.) N.E.Br.…”

“…It is estimated that about 25% of medicines are derived directly or indirectly from herbal products (Kunle et al, 2012). Within the group of natural products, essential oils (EOs) have been of interest because of their broad spectrum of reported biological properties (Kulevanova et al, 2000;Rhayour et al, 2003), including leishmanicidal activity (de Medeiros et al, 2011;Rodrigues et al, 2013;Colares et al, 2013;Monzote et al, 2014a,b). In addition, their hydrophobic nature makes these oils more permeable to cells (Burt, 2004), which is a very important feature for developing agents against intracellular pathogens.…”