Arrabidaea chicaHexanic Extract Induces Mitochondrion Damage and Peptidase Inhibition onLeishmaniaspp.

Abstract

Currently available leishmaniasis treatments are limited due to severe side effects. Arrabidaea chica is a medicinal plant used in Brazil against several diseases. In this study, we investigated the effects of 5 fractions obtained from the crude hexanic extract of A. chica against Leishmania amazonensis and L. infantum, as well as on the interaction of these parasites with host cells. Promastigotes were treated with several concentrations of the fractions obtained from A. chica for determination of their minimum inhibitory concentration (MIC). In addition, the effect of the most active fraction (B2) on parasite's ultrastructure was analyzed by transmission electron microscopy. To evaluate the inhibitory activity of B2 fraction on Leishmania peptidases, parasites lysates were treated with the inhibitory and subinhibitory concentrations of the B2 fraction. The minimum inhibitory concentration of B2 fraction was 37.2 and 18.6 μg/mL for L. amazonensis and L. infantum, respectively. Important ultrastructural alterations as mitochondrial swelling with loss of matrix content and the presence of vesicles inside this organelle were observed in treated parasites. Moreover, B2 fraction was able to completely inhibit the peptidase activity of promastigotes at pH 5.5. The results presented here further support the use of A. chica as an interesting source of antileishmanial agents.

A Triazole Hybrid of Neolignans as a Potential Antileishmanial Agent by Triggering Mitochondrial Dysfunction

“…Apoptosis and necrosis induce the transition of mitochondrial membrane permeability (MPT), which results from the opening of a high conduction pore on the inner mitochondrial membrane. Mitochondria is a potential target for antileishmanial drugs and this mechanism of action has been widely described [11,12,26,27]. The single mitochondria of the kinetoplastid parasite and its functional features are markedly distinct from the mammalian ones [28].…”

“…Nevertheless, the hypothesis of an autophagy cannot be discarded. In this process, characteristic autophagic vacuoles encompass lipids that were not incorporated into the cellular membranes [26]. Interestingly, autophagic cell death may arise as a consequence of mitochondrial stress [29].…”

Ethnobotanical study of medicinal plants by population of Valley of Juruena Region, Legal Amazon, Mato Grosso, Brazil

“…The activities include among others, hepatoprotective (hydroethanolic extract), antimicrobial (hydroethanolic and dichloromethane extracts), wound healing (methanolic and ethanolic extracts), anti-inflammatory (aqueous extract), analgesic, antihelminthic and anti-Leshmania activities (hexanic extract) (Barbosa et al, 2008;Höfling et al, 2010;Mafioleti et al, 2013;Paula et al, 2014;Rodrigues et al, 2014). Recently also the ethanol and aqueous extracts of Arrabidaea chica were shown to be anti-inflammatory, antiangiogenic and antiproliferative activities in a murine model (Michel et al, 2015).…”

Antileishmanial effects of the alkaloid-rich fraction of Quassia amara L.

“…Plant-derived products, extracts or isolated substances can inhibit Leishmania sterol biosynthesis. Previously, our group reported that a fraction (B2) obtained from the hexane extract of Arrabidaea chica caused similar damages to L. infantum promastigotes (Rodrigues et al, 2014). L. amazonensis treatment with 1 to 5 µM tomatidine, a tomato alkaloid, led to the inhibition of Δ24(25)-sterol methyltransferase, an essential enzyme for the ergosterol production (Medina et al, 2012).…”