Interaction of ascaridole, carvacrol, and caryophyllene oxide from essential oil of Chenopodium ambrosioides L. with mitochondria in Leishmania and other eukaryotes

Abstract

The antileishmanial activity of the essential oil (EO) from Chenopodium ambrosioides L. has been demonstrated in vitro and in animal models, attributed to the major components of the EO. This study focused on the effects of the three major EO compounds carvacrol, caryophyllene oxide (Caryo), and the antileishmanial endoperoxide ascaridole (Asc) on mitochondrial functions in Leishmania tarentolae promastigotes (LtP). EO and Caryo were able to partially inhibit the leishmanial electron transport chain, whereas other components failed to demonstrate a direct immediate effect. Caryo demonstrated inhibition of complex III activity in LtP and in isolated complex III from other species. The formation of superoxide radicals was studied in Leishmania by electron spin resonance spectroscopy in the presence of iron chelators wherein selected compounds failed to trigger a significant immediate additional superoxide production in LtP. However, upon prolonged incubation of Leishmania with Asc and especially in the absence of iron chelators (allowing the activation of Asc), an increased superoxide radical production and significant impairment of mitochondrial coupling in Leishmania was observed. Prolonged incubation with all EO components resulted in thiol depletion. Taken together, the major components of EO mediate their leishmanicidal activity via different mitochondrial targets and time profiles. Further studies are required to elucidate possible synergistic effects of carvacrol and Asc and the influence of minor compounds.

Essential Oils from Croton Species: Chemical Composition, in vitro and in silico Antileishmanial Evaluation, Antioxidant and Cytotoxicity Activities

“…44 Caryophyllene oxide exerts action on mitochondrial functions in Leishmania tarentolae promastigotes (LtP) and was able to partially inhibit the leishmanial electron transport chain. 45 The immunomodulatory activity of spathulenol present in Salvia mirzayanii 46 is an important characteristic for antileishmanial action. Several clinical trials have established potent anti-inflammatory activity of 1,8-cineole, which suggests its use as a primary treatment or as adjunct therapy with current anti-inflammatory agents.…”

Active Essential Oils and Their Components in Use against Neglected Diseases and Arboviruses

“…This ability to control disease progression of cutaneous leishmaniasis was also observed with EO from Bixa orellana , at dose of 30 mg/kg over 14 days [181]. Finally, recent studies suggested that Ca EO caused a breakdown of mitochondrial membrane potential and a modification of redox indexes [64], and the isolated compounds carvacrol ( 10 ), ascaridole ( 37 ), and caryophyllene oxide ( 38 ) mediated their leishmanicidal activity via various mitochondrial targets, including the electron transport chain, thiol depletion, and production of superoxide radical, causing significant impairment of mitochondrial coupling [182].…”

Chemical Constituents with Leishmanicidal Activity from a Pink-Yellow Cultivar of Lantana camara var. aculeata (L.) Collected in Central Mexico

“…Caryophyllene oxide ( 4 ) was extensively studied by Monzote and collaborators, who evaluated it against L. amazonensis (MHOM/BR/77/LTB0016; IC 50 = 22.2 ± 10.4 μM for promastigotes; IC 50 = 20 ± 1.8 μM for amastigotes) [ 56 ] and L. tarentolae , a Sauroleishmania species, (P10; IC 50 = 36.0 ± 17.6 μM for promastigotes) [ 57 ]. They proposed that the leishmanicidal mechanism of action of this compound involved an enhancement of superoxide radicals, a decrease in promastigote oxygen consumption, and the inhibition of the mitochondrial electron transport chain complex III [ 57 ].…”