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Lianet Monzote - One of the best experts on this subject based on the ideXlab platform.

  • activation of artemisinin and heme degradation in leishmania tarentolae promastigotes a possible link
    Biochemical Pharmacology, 2020
    Co-Authors: Gerald Geroldinger, Lianet Monzote, Matthias Tonner, Sritama De Sarkar, Judith Quirgst, Martin Walter, Laura Machin, Klaus Stolze, Catharina J Duvigneau, Katrin Staniek
    Abstract:

    Abstract Endoperoxides (EPs) appear to be promising drug candidates against protozoal diseases, including malaria and leishmaniasis. Previous studies have shown that these drugs need an intracellular activation to exert their pharmacological potential. The efficiency of these drugs is linked to the extensive iron demand of these intracellular protozoal parasites. An essential step of the activation mechanism of these drugs is the formation of radicals in Leishmania. Iron is a known trigger for intracellular radical formation. However, the activation of EPs by low molecular iron or by heme iron may strongly depend on the structure of the EPs themselves. In this study, we focused on the activation of artemisinin (Art) in Leishmania tarentolae promastigotes (LtP) in comparison to reference compounds. Viability assays in different media in the presence of different iron sources (hemin/fetal calf serum) showed that IC50 values of Art in LtP were modulated by assay conditions, but overall were within the low micromolar range. Low temperature electron paramagnetic resonance (EPR) spectroscopy of LtP showed that Art shifted the redox state of the labile iron pool less than the EP Ascaridole questioning its role as a major activator of Art in LtP. Based on the high reactivity of Art with hemin in previous biomimetic experiments, we focused on putative heme-metabolizing enzymes in Leishmania, which were so far not well described. Inhibitors of mammalian heme oxygenase (HO; tin and chromium mesoporphyrin) acted antagonistically to Art in LtP and boosted its IC50 value for several magnitudes. By inductively coupled plasma methods (ICP-OES, ICP-MS) we showed that these inhibitors do not block iron (heme) accumulation, but are taken up and act within LtP. These inhibitors blocked the conversion of hemin to bilirubin in LtP homogenates, suggesting that an HO-like enzyme activity in LtP exists. NADPH-dependent degradation of Art and hemin was highest in the small granule and microsomal fractions of LtP. Photometric measurements in the model Art/hemin demonstrated that hemin requires reduction to heme and that subsequently an Art/heme complex (λmax 474 nm) is formed. EPR spin-trapping in the system Art/hemin revealed that NADPH, ascorbate and cysteine are suitable reductants and finally activate Art to acyl-carbon centered radicals. These findings suggest that heme is a major activator of Art in LtP either via HO-like enzyme activities and/or chemical interaction of heme with Art.

  • interaction of Ascaridole carvacrol and caryophyllene oxide from essential oil of chenopodium ambrosioides l with mitochondria in leishmania and other eukaryotes
    Phytotherapy Research, 2018
    Co-Authors: Lianet Monzote, Ramon Scull, Katrin Staniek, Gerald Geroldinger, Matthias Tonner, Sritama De Sarkar, Sophie Bergmann, Markus Bacher, Mitali Chatterjee, Thomas Rosenau
    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.

  • combinations of Ascaridole carvacrol and caryophyllene oxide against leishmania
    Acta Tropica, 2015
    Co-Authors: Jacinta Pastor, Marley Garcia, Silvia Steinbauer, Ramon Scull, William N Setzer, Lars Gille, Lianet Monzote
    Abstract:

    Abstract To date there are no vaccines against Leishmania and chemotherapy remains the mainstay for the control of leishmaniasis. The drugs currently used for leishmaniasis therapy are significantly toxic, expensive, and result in a growing frequency of refractory infections. In this study, we evaluated the effect of combinations of the main components of essential oil from Chenopodium ambrosioides (Ascaridole, carvacrol, and caryophyllene oxide) against Leishmania amazonensis. Anti-leishmanial effects of combinations of pure compounds were evaluated in vitro and the fractional inhibitory concentration (FIC) indices were calculated. BALB/c mice infected with L. amazonensis were treated with different concentrations of Ascaridole–carvacrol combinations by intralesional doses every 4 days. Disease progression and parasite burden in infected tissues were determined. In vitro experiments showed a synergistic effect of the combination of Ascaridole–carvacrol against promastigotes of Leishmania with a FIC index of 0.171, while indifferent activities were observed for Ascaridole–caryophyllene oxide (FIC index = 3.613) and carvacrol–caryophyllene oxide (FIC index = 2.356) combinations. The fixed ratio method showed that a 1:4 Ascaridole–carvacrol ratio produced a better anti-protozoal activity on promastigotes, lower cytotoxicity, and synergistic activity on intracellular amastigotes (FIC index = 0.416). Significant differences (p

  • combinations of Ascaridole carvacrol and caryophyllene oxide against leishmania
    Acta Tropica, 2015
    Co-Authors: Jacinta Pastor, Marley Garcia, Silvia Steinbauer, Ramon Scull, William N Setzer, Lars Gille, Lianet Monzote
    Abstract:

    To date there are no vaccines against Leishmania and chemotherapy remains the mainstay for the control of leishmaniasis. The drugs currently used for leishmaniasis therapy are significantly toxic, expensive, and result in a growing frequency of refractory infections. In this study, we evaluated the effect of combinations of the main components of essential oil from Chenopodium ambrosioides (Ascaridole, carvacrol, and caryophyllene oxide) against Leishmaniaamazonensis. Anti-leishmanial effects of combinations of pure compounds were evaluated in vitro and the fractional inhibitory concentration (FIC) indices were calculated. BALB/c mice infected with L. amazonensis were treated with different concentrations of Ascaridole-carvacrol combinations by intralesional doses every 4 days. Disease progression and parasite burden in infected tissues were determined. In vitro experiments showed a synergistic effect of the combination of Ascaridole-carvacrol against promastigotes of Leishmania with a FIC index of 0.171, while indifferent activities were observed for Ascaridole-caryophyllene oxide (FIC index=3.613) and carvacrol-caryophyllene oxide (FIC index=2.356) combinations. The fixed ratio method showed that a 1:4 Ascaridole-carvacrol ratio produced a better anti-protozoal activity on promastigotes, lower cytotoxicity, and synergistic activity on intracellular amastigotes (FIC index=0.416). Significant differences (p<0.05) in lesion size and parasite burden were demonstrated in BALB/c mice experimentally infected and treated with the Ascaridole-carvacrol combinations compared with control animals. Carvacrol showed significant higher anti-radical activity in the DPPH assay compared with caryophyllene oxide. Electron spin resonance spectroscopy in combination with spin trapping suggested the presence of carbon-centered radicals after activation of Ascaridole by Fe(2+). The intensity of the signals is preferably decreased upon addition of carvacrol. The Ascaridole-carvacrol combination could represent a future alternative to monotherapeutic anti-leishmanial agents.

  • antileishmanial activity of essential oil from chenopodium ambrosioides and its main components against experimental cutaneous leishmaniasis in balb c mice
    Phytomedicine, 2014
    Co-Authors: Lianet Monzote, Jacinta Pastor, Ramon Scull, Lars Gille
    Abstract:

    Abstract Chenopodium ambrosioides have been used during centuries by native people to treat parasitic diseases. Aims of the study To compare the in vivo anti-leishmanial activity of the essential oil (EO) from C. ambrosioides and its major components (Ascaridole, carvacrol and caryophyllene oxide). Materials and methods Anti-leishmanial effect was evaluated in BALB/c mice infected with Leishmania amazonensis and treated with the EO, main compounds and artificial mix of pure components by intralesional route at 30 mg/kg every 4 days during 14 days. Diseases progression and parasite burden in infected tissues were determined. Results EO prevented lesion development compared ( p p Conclusions Our results demonstrate the superiority of EO against experimental cutaneous leishmaniasis caused by L. amazonensis .

Joseph Casanova - One of the best experts on this subject based on the ideXlab platform.

Lars Gille - One of the best experts on this subject based on the ideXlab platform.

  • oxidative stress mediated anti leishmanial activity of endoperoxides represent a new therapeutic strategy in leishmaniasis
    Free Radical Biology and Medicine, 2018
    Co-Authors: Mitali Chatterjee, Katrin Staniek, Gerald Geroldinger, Matthias Tonner, Sritama De Sarkar, Lars Gille
    Abstract:

    Endoperoxides kill malaria parasites via cleavage of their endoperoxide bridge by heme or iron, leading to generation of cytotoxic oxygen-centered radicals. In view of the impaired anti-oxidant defense and high iron content of Leishmania parasites, the effectiveness of two endoperoxides, artemisinin and Ascaridole was evaluated. Both demonstrated parasiticidal activity (in Leishmania donovani, LD and Leishmania tarentolae, LtP), along with lower cytotoxicity in macrophages. In LtP, carbon-centered radicals were identified in the presence of both endoperoxides by ESR spin-trapping and downstream formation of reactive oxygen species confirmed by flow cytometry. We explored whether leishmanial mitochondria are a target for this secondary oxygen radical formation. Both endoperoxides minimally impaired the electron transport chain, but impaired mitochondrial coupling upon prolonged exposure. Additionally, artemisinin depleted ATP levels, increased ATPase activity and enhanced Ca2+ release which collectively translated into a caspase-independent apoptotic-like cell death. Collectively, the endoperoxide-mediated radical formation was the initial step for their antileishmanial activity and represents a promising therapeutic strategy worthy of pharmacological consideration.

  • combinations of Ascaridole carvacrol and caryophyllene oxide against leishmania
    Acta Tropica, 2015
    Co-Authors: Jacinta Pastor, Marley Garcia, Silvia Steinbauer, Ramon Scull, William N Setzer, Lars Gille, Lianet Monzote
    Abstract:

    Abstract To date there are no vaccines against Leishmania and chemotherapy remains the mainstay for the control of leishmaniasis. The drugs currently used for leishmaniasis therapy are significantly toxic, expensive, and result in a growing frequency of refractory infections. In this study, we evaluated the effect of combinations of the main components of essential oil from Chenopodium ambrosioides (Ascaridole, carvacrol, and caryophyllene oxide) against Leishmania amazonensis. Anti-leishmanial effects of combinations of pure compounds were evaluated in vitro and the fractional inhibitory concentration (FIC) indices were calculated. BALB/c mice infected with L. amazonensis were treated with different concentrations of Ascaridole–carvacrol combinations by intralesional doses every 4 days. Disease progression and parasite burden in infected tissues were determined. In vitro experiments showed a synergistic effect of the combination of Ascaridole–carvacrol against promastigotes of Leishmania with a FIC index of 0.171, while indifferent activities were observed for Ascaridole–caryophyllene oxide (FIC index = 3.613) and carvacrol–caryophyllene oxide (FIC index = 2.356) combinations. The fixed ratio method showed that a 1:4 Ascaridole–carvacrol ratio produced a better anti-protozoal activity on promastigotes, lower cytotoxicity, and synergistic activity on intracellular amastigotes (FIC index = 0.416). Significant differences (p

  • combinations of Ascaridole carvacrol and caryophyllene oxide against leishmania
    Acta Tropica, 2015
    Co-Authors: Jacinta Pastor, Marley Garcia, Silvia Steinbauer, Ramon Scull, William N Setzer, Lars Gille, Lianet Monzote
    Abstract:

    To date there are no vaccines against Leishmania and chemotherapy remains the mainstay for the control of leishmaniasis. The drugs currently used for leishmaniasis therapy are significantly toxic, expensive, and result in a growing frequency of refractory infections. In this study, we evaluated the effect of combinations of the main components of essential oil from Chenopodium ambrosioides (Ascaridole, carvacrol, and caryophyllene oxide) against Leishmaniaamazonensis. Anti-leishmanial effects of combinations of pure compounds were evaluated in vitro and the fractional inhibitory concentration (FIC) indices were calculated. BALB/c mice infected with L. amazonensis were treated with different concentrations of Ascaridole-carvacrol combinations by intralesional doses every 4 days. Disease progression and parasite burden in infected tissues were determined. In vitro experiments showed a synergistic effect of the combination of Ascaridole-carvacrol against promastigotes of Leishmania with a FIC index of 0.171, while indifferent activities were observed for Ascaridole-caryophyllene oxide (FIC index=3.613) and carvacrol-caryophyllene oxide (FIC index=2.356) combinations. The fixed ratio method showed that a 1:4 Ascaridole-carvacrol ratio produced a better anti-protozoal activity on promastigotes, lower cytotoxicity, and synergistic activity on intracellular amastigotes (FIC index=0.416). Significant differences (p<0.05) in lesion size and parasite burden were demonstrated in BALB/c mice experimentally infected and treated with the Ascaridole-carvacrol combinations compared with control animals. Carvacrol showed significant higher anti-radical activity in the DPPH assay compared with caryophyllene oxide. Electron spin resonance spectroscopy in combination with spin trapping suggested the presence of carbon-centered radicals after activation of Ascaridole by Fe(2+). The intensity of the signals is preferably decreased upon addition of carvacrol. The Ascaridole-carvacrol combination could represent a future alternative to monotherapeutic anti-leishmanial agents.

  • antileishmanial activity of essential oil from chenopodium ambrosioides and its main components against experimental cutaneous leishmaniasis in balb c mice
    Phytomedicine, 2014
    Co-Authors: Lianet Monzote, Jacinta Pastor, Ramon Scull, Lars Gille
    Abstract:

    Abstract Chenopodium ambrosioides have been used during centuries by native people to treat parasitic diseases. Aims of the study To compare the in vivo anti-leishmanial activity of the essential oil (EO) from C. ambrosioides and its major components (Ascaridole, carvacrol and caryophyllene oxide). Materials and methods Anti-leishmanial effect was evaluated in BALB/c mice infected with Leishmania amazonensis and treated with the EO, main compounds and artificial mix of pure components by intralesional route at 30 mg/kg every 4 days during 14 days. Diseases progression and parasite burden in infected tissues were determined. Results EO prevented lesion development compared ( p p Conclusions Our results demonstrate the superiority of EO against experimental cutaneous leishmaniasis caused by L. amazonensis .

  • essential oil from chenopodium ambrosioides and main components activity against leishmania their mitochondria and other microorganisms
    Experimental Parasitology, 2014
    Co-Authors: Lianet Monzote, Jacinta Pastor, Marley Garcia, Ramon Scull, Louis Maes, Lars Gille
    Abstract:

    Abstract Chenopodium ambrosioides is an aromatic herb used by native people to treat parasitic diseases. The aim of this work is to compare the in vitro anti-leishmanial activity of the essential oil (EO) from C. ambrosioides and its major components (Ascaridole, carvacrol and caryophyllene oxide) and study their mechanism of action and activity against a panel of microorganism. Antileishmanial activity and cytotoxicity of the EO and major components was study. In addition, experiments to elucidate the mechanism of action were perform and activities against other microorganisms (bacteria, fungi and protozoa) were evaluate. All products were active against promastigote and amastigote forms of Leishmania. Ascaridole exhibited the better antileishmanial activity and the EO the highest selectivity index. The exploration of the mechanism suggests that the products cause a breakdown of mitochondrial membrane potential and a modification of redox indexes. Only EO showed antiprotozoal effect against Plasmodium falciparum and Trypanosoma brucei; while no activity against bacteria and fungi was observed. Our results demonstrate the potentialities of EO in cellular and molecular system, which could be consider in future studies to develop new antileishmanial drugs with a wide anti-parasitic spectrum.

Filippo Maggi - One of the best experts on this subject based on the ideXlab platform.

  • Exploring the Insecticidal Potential of Boldo (Peumus boldus) Essential Oil: Toxicity to Pests and Vectors and Non-target Impact on the Microcrustacean Daphnia magna.
    Molecules, 2019
    Co-Authors: Roman Pavela, Giulio Lupidi, Stefano Dall’acqua, Riccardo Petrelli, Loredana Cappellacci, Giovanni Benelli, Filippo Maggi
    Abstract:

    Every year Chile exports about 2000 tons of boldo folium (Peumus boldus), which is used around the world as a traditional herbal medicinal product (THMP), mostly to relieve gastrointestinal disorders. This biomass may be a resource for the agrochemical industry to manufacture botanical insecticides. In this regard, the insecticidal potential of boldo has been poorly investigated. In the present work, hydrodistillation of a commercial boldo folium gave 1.5% (w/w) of a yellowish essential oil (boldo essential oil, BEO) containing 1,8-cineole (20.7%), p-cymene (18.5%), limonene (9.1%), Ascaridole (9.1%) and β-phellandrene (6.4%) as the main constituents, as determined by gas chromatography-mass spectrometry (GC-MS). NMR analysis allowed us to determine that Ascaridole was mainly represented by the cis-isomer. BEO was toxic to larvae of the filariasis vector Culex quinquefasciatus and adults of the housefly Musca domestica, showing LC50/LD50 values of 67.9 mg·L−1 and 98.5 µg·adult−1, respectively. On the other hand, lower insecticidal activity was observed against larvae of the moth pest Spodoptera littoralis (LD50 of 268.9 µg·larva−1). It is worth noting that, when tested at LC90 concentration, BEO was significantly less toxic to aquatic microcrustacean Daphnia magna than the conventional insecticide α-cypermethrin. Finally, in the attempt to explore the BEO mode of action, we tested it for acetylcholinesterase (AChE) inhibitory properties using the Ellman method, obtaining negligible effects (IC50 = 0.45 mg·mL−1). Taken together, these results gave new insights into the potential of BEO as a future ingredient of botanical insecticides.

  • Exploring the Insecticidal Potential of Boldo (Peumus boldus) Essential Oil: Toxicity to Pests and Vectors and Non-target Impact on the Microcrustacean Daphnia magna
    MDPI AG, 2019
    Co-Authors: Roman Pavela, Giulio Lupidi, Stefano Dall’acqua, Riccardo Petrelli, Loredana Cappellacci, Giovanni Benelli, Stefania Sut, Filippo Maggi
    Abstract:

    Every year Chile exports about 2000 tons of boldo folium (Peumus boldus), which is used around the world as a traditional herbal medicinal product (THMP), mostly to relieve gastrointestinal disorders. This biomass may be a resource for the agrochemical industry to manufacture botanical insecticides. In this regard, the insecticidal potential of boldo has been poorly investigated. In the present work, hydrodistillation of a commercial boldo folium gave 1.5% (w/w) of a yellowish essential oil (boldo essential oil, BEO) containing 1,8-cineole (20.7%), p-cymene (18.5%), limonene (9.1%), Ascaridole (9.1%) and β-phellandrene (6.4%) as the main constituents, as determined by gas chromatography-mass spectrometry (GC-MS). NMR analysis allowed us to determine that Ascaridole was mainly represented by the cis-isomer. BEO was toxic to larvae of the filariasis vector Culex quinquefasciatus and adults of the housefly Musca domestica, showing LC50/LD50 values of 67.9 mg·L−1 and 98.5 µg·adult−1, respectively. On the other hand, lower insecticidal activity was observed against larvae of the moth pest Spodoptera littoralis (LD50 of 268.9 µg·larva−1). It is worth noting that, when tested at LC90 concentration, BEO was significantly less toxic to aquatic microcrustacean Daphnia magna than the conventional insecticide α-cypermethrin. Finally, in the attempt to explore the BEO mode of action, we tested it for acetylcholinesterase (AChE) inhibitory properties using the Ellman method, obtaining negligible effects (IC50 = 0.45 mg·mL−1). Taken together, these results gave new insights into the potential of BEO as a future ingredient of botanical insecticides

  • Clausena anisata and Dysphania ambrosioides essential oils: from ethno-medicine to modern uses as effective insecticides
    Environmental Science and Pollution Research, 2018
    Co-Authors: Roman Pavela, Giulio Lupidi, Filippo Maggi, Hélène Mbuntcha, Verlaine Woguem, Hilaire Macaire Womeni, Luciano Barboni, Léon Azefack Tapondjou, Giovanni Benelli
    Abstract:

    Dysphania ambrosioides (L.) Mosyakin & Clemants (Amaranthaceae) and Clausena anisata (Willd.) Hook. f. ex Benth. (Rutaceae) are two aromatic species traditionally used in Cameroon to repel and kill insects. The present work was carried out to substantiate this traditional use and to evaluate the possible incorporation in commercial botanical insecticides of their essential oils (EOs). The EOs were distilled from leaves of C. anisata and aerial parts of D. ambrosioides and analyzed by gas chromatography-mass spectrometry (GC-MS). The insecticidal activity of both EOs was investigated against the filariasis vector, Culex quinquefasciatus , and the housefly, Musca domestica . As possible mode of action, the inhibition of acetylcholinesterase (AChE) by the two EOs was investigated as well. The D. ambrosioides EO was characterized by the monoterpene peroxide Ascaridole (61.4%) and the aromatic p -cymene (29.0%), whereas the C. anisata EO was dominated by the phenylpropanoids ( E )-anethole (64.6%) and ( E )-methyl isoeugenol (16.1%). The C. anisata EO proved to be very toxic to third instar larvae of C. quinquefasciatus showing LC_50 of 29.3 μl/l, whereas D. ambrosioides EO was more toxic to adults of M. domestica showing a LD_50 of 51.7 μg/adult. The mixture of both EOs showed a significant synergistic effect against mosquito larvae with LC_50 estimated as 19.3 μl/l, whereas this phenomenon was not observed upon application to M. domestica adults (LD_50 = 75.9 μg/adult). Of the two EOs, the D. ambrosioides one provided a good inhibition of AChE (IC_50 = 77 μg/ml), whereas C. anisata oil was not effective. These findings provide new evidences supporting the ethno-botanical use of these two Cameroonian plants, and their possible application even in synergistic binary blends, to develop new eco-friendly, safe and effective herbal insecticides.

Jeanfrancois Cavalli - One of the best experts on this subject based on the ideXlab platform.

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