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Lenka Skalova - One of the best experts on this subject based on the ideXlab platform.

  • the impact of sesquiterpenes β Caryophyllene Oxide and trans nerolidol on xenobiotic metabolizing enzymes in mice in vivo
    Xenobiotica, 2018
    Co-Authors: Kateřina Lněnickova, Hana Svobodova, Lenka Skalova, Martin Ambrož, Filip Novak, Petra Matouskova
    Abstract:

    Abstract1. Sesquiterpenes, constituents of plant essential oil, are popular bioactive compounds due to the positive effect on human health, but their potential toxicity and possible herb-drug interactions are often omitted. In our in vivo study, we followed up the effect of p.o. administration of two sesquiterpenes β-Caryophyllene Oxide (CAO) and trans-nerolidol (NER) on various xenobiotic-metabolizing enzymes in mice liver and small intestine.2. To spot the early effect of studied compounds, enzymatic activity and mRNA levels were assessed 6 and 24 h after single dose.3. CAO and NER markedly increased cytochromes P450 (CYP2B, 3A, 2C) activity and mRNA levels in both tissues. Liver also showed elevated activity of aldo-ketoreductase 1C and carbonyl reductase after treatment. Contrary, sesquiterpenes decreased NAD(P)H:quinone oxidoreductase 1 activity in small intestine. Among conjugation enzymes, only liver sulfotransferase activity was increased by sesquiterpenes.4. Our results document that single dose ...

  • the inhibitory effects of β Caryophyllene β Caryophyllene Oxide and α humulene on the activities of the main drug metabolizing enzymes in rat and human liver in vitro
    Chemico-Biological Interactions, 2017
    Co-Authors: Linh Thuy Nguyen, Kateřina Lněnickova, Martin Ambrož, Pavel Anzenbacher, Zuzana Mysliveckova, Barbora Szotakova, Alena Spicakova, Vladimir Kubicek, Kristýna Krasulova, Lenka Skalova
    Abstract:

    Abstract Sesquiterpenes, the main components of plant essential oils, are often taken in the form of folk medicines and dietary supplements. Several sesquiterpenes possess interesting biological activities but they could interact with concurrently administered drugs via inhibition of drug-metabolizing enzymes. Therefore, the present study was designed to test the potential inhibitory effect of tree structurally relative sesquiterpenes β-Caryophyllene (CAR), β-Caryophyllene Oxide (CAO) and α-humulene (HUM) on the activities of the main drug-metabolizing enzymes. For this purpose, rat and human hepatic subcellular fractions were incubated with CAR, CAO or HUM together with specific substrates for oxidation, reduction and conjugation enzymes and their coenzymes. HPLC, spectrophotometric and spectrofluorimetric analyses of product formations were used. All tested sesquiterpenes significantly inhibited cytochromes P4503A (CYP3A) activities in rats as well as in human hepatic microsomes, with CAO being the strongest inhibitor. A non-competitive type of inhibition was found. On the other hand, none of the tested sesquiterpenes significantly affected the activities of carbonyl-reducing enzymes (CBR1, AKRs, NQO1) or conjugation enzymes (UGTs, GSTs, SULTs, COMT). As CYP3A enzymes metabolize many drugs, their inhibition by CAO, CAR and HUM might affect the pharmacokinetics of concurrently administered drugs. Similar results obtained in rat and human hepatic microsomes indicate that rats could be used for further testing of possible drug-sesquiterpenes interactions in vivo.

  • the effects of β Caryophyllene Oxide and trans nerolidol on the efficacy of doxorubicin in breast cancer cells and breast tumor bearing mice
    Biomedicine & Pharmacotherapy, 2017
    Co-Authors: Veronika Hanusova, Hana Svobodova, Martin Ambrož, Kateřina Caltova, Adam Skarka, Natalie Murinova, Věra Kralova, Pavel Tomsik, Lenka Skalova
    Abstract:

    Abstract Background One approach to improve effect of chemotherapy is combination of classical cytostatic drugs with natural compounds, e. g. sesquiterpenes. In our previous study, sesquiterpenes β-Caryophyllene Oxide (CAO) and trans-nerolidol (NER) improved the anti-proliferative effect of doxorubicin (DOX) in intestinal cancer cell lines. Purpose The present study was designed to evaluate the effect of CAO and NER on DOX efficacy, focusing on cell proliferation, migration, apoptosis and DOX accumulation in breast cancer cells MDA-MB-231 and MCF7 in vitro and in mice bearing solid Ehrlich tumors (EST) in vivo. Methods The impact of cytotoxic effect was assessed by the neutral red uptake test. The ability to migrate was tested using real-time measurement in x-CELLigence system. Expressions of molecules were examined using western blot analysis. The accumulation of DOX inside the cells using time lapse microscopy was observed. The mice with inoculated EST cells were treated repeatedly with DOX and DOX + CAO or DOX + NER and the growth of tumors were monitored. DOX concentrations in plasma and tumor were assayed using HPLC. Results In MDA-MB-231, combination of DOX with CAO enhanced anti-proliferative effect and acted strongly synergistic. NER increased accumulation of DOX inside the cells; moreover combination DOX with NER suppressed migration ability in vitro. In vivo, apoptosis was activated especially in group treated with DOX and CAO. However, none of tested sesquiterpenes was able to improve DOX accumulation in tumors and DOX-mediated inhibition of tumor growth. Conclusion In conclusion, sesquiterpenes CAO and NER increased the efficacy of DOX in breast cancer cells in vitro, but did not improve its effect in vivo, in Ehrlich solid tumor bearing mice.

Luis M Penarodriguez - One of the best experts on this subject based on the ideXlab platform.

  • synergistic effect of lupenone and Caryophyllene Oxide against trypanosoma cruzi
    Evidence-based Complementary and Alternative Medicine, 2013
    Co-Authors: Glendy Polancohernandez, Fabiola Escalanteerosa, Karlina Garciasosa, Maria E Rosado, Eugenia Guzmanmarin, Karla Y Acostaviana, Alberto Gimenezturba, Efrain Salamanca, Luis M Penarodriguez
    Abstract:

    The in vitro trypanocidal activity of a 1 : 4 mixture of lupenone and Caryophyllene Oxide confirmed a synergistic effect of the terpenoids against epimastigotes forms of T. cruzi ( μg/mL, FIC = 0.46). In addition, testing of the terpenoid mixture for its capacity to reduce the number of amastigote nests in cardiac tissue and skeletal muscle of infected mice showed a reduction of more than 80% at a dose level of 20.8 mg·kg−1·day−1.

Liliana Torcoroma Garcia - One of the best experts on this subject based on the ideXlab platform.

  • induction of programmed cell death in trypanosoma cruzi by lippia alba essential oils and their major and synergistic terpenes citral limonene and Caryophyllene Oxide
    BMC Complementary and Alternative Medicine, 2018
    Co-Authors: Erika Marcela Moreno, Sandra Milena Leal, Elena E Stashenko, Liliana Torcoroma Garcia
    Abstract:

    Chagas Disease caused by Trypanosoma cruzi infection, is one of the most important neglected tropical diseases (NTD), without an effective therapy for the successful parasite eradication or for the blocking of the disease’s progression, in its advanced stages. Due to their low toxicity, wide pharmacologic spectrum, and potential synergies, medicinal plants as Lippia alba, offer a promising reserve of bioactive molecules. The principal goal of this work is to characterize the inhibitory properties and cellular effects of the Citral and Carvone L. alba chemotype essential oils (EOs) and their main bioactive terpenes (and the synergies among them) on T. cruzi forms. Twelve L. alba EOs, produced under diverse environmental conditions, were extracted by microwave assisted hydrodistillation, and chemically characterized using gas chromatography coupled mass spectrometry. Trypanocidal activity and cytotoxicity were determined for each oil, and their major compounds, on epimastigotes (Epi), trypomastigotes (Tryp), amastigotes (Amas), and Vero cells. Pharmacologic interactions were defined by a matrix of combinations among the most trypanocidal terpenes (limonene, carvone; citral and Caryophyllene Oxide). The treated cell phenotype was assessed by fluorescent and optic microscopy, flow cytometry, and DNA electrophoresis assays. The L. alba EOs displayed significant differences in their chemical composition and trypanocidal performance (p = 0.0001). Citral chemotype oils were more trypanocidal than Carvone EOs, with Inhibitory Concentration 50 (IC50) of 14 ± 1.5 μg/mL, 22 ± 1.4 μg/mL and 74 ± 4.4 μg/mL, on Epi, Tryp and Amas, respectively. Limonene exhibited synergistic interaction with citral, Caryophyllene Oxide and Benznidazole (decreasing by 17 times its IC50) and was the most effective and selective treatment. The cellular analysis suggested that these oils or their bioactive terpenes (citral, Caryophyllene Oxide and limonene) could be inducing T. cruzi cell death by an apoptotic-like mechanism. EOs extracted from L. alba Citral chemotype demonstrated significant trypanocidal activity on the three forms of T. cruzi studied, and their composition and trypanocidal performance were influenced by production parameters. Citral, Caryophyllene Oxide, and limonene showed a possible induction of an apoptotic-like phenotype. The best selective anti-T. cruzi activity was achieved by limonene, the effects of which were also synergic with citral, Caryophyllene Oxide and benznidazole.

A V Kutchin - One of the best experts on this subject based on the ideXlab platform.

Martin Ambrož - One of the best experts on this subject based on the ideXlab platform.

  • the impact of sesquiterpenes β Caryophyllene Oxide and trans nerolidol on xenobiotic metabolizing enzymes in mice in vivo
    Xenobiotica, 2018
    Co-Authors: Kateřina Lněnickova, Hana Svobodova, Lenka Skalova, Martin Ambrož, Filip Novak, Petra Matouskova
    Abstract:

    Abstract1. Sesquiterpenes, constituents of plant essential oil, are popular bioactive compounds due to the positive effect on human health, but their potential toxicity and possible herb-drug interactions are often omitted. In our in vivo study, we followed up the effect of p.o. administration of two sesquiterpenes β-Caryophyllene Oxide (CAO) and trans-nerolidol (NER) on various xenobiotic-metabolizing enzymes in mice liver and small intestine.2. To spot the early effect of studied compounds, enzymatic activity and mRNA levels were assessed 6 and 24 h after single dose.3. CAO and NER markedly increased cytochromes P450 (CYP2B, 3A, 2C) activity and mRNA levels in both tissues. Liver also showed elevated activity of aldo-ketoreductase 1C and carbonyl reductase after treatment. Contrary, sesquiterpenes decreased NAD(P)H:quinone oxidoreductase 1 activity in small intestine. Among conjugation enzymes, only liver sulfotransferase activity was increased by sesquiterpenes.4. Our results document that single dose ...

  • the inhibitory effects of β Caryophyllene β Caryophyllene Oxide and α humulene on the activities of the main drug metabolizing enzymes in rat and human liver in vitro
    Chemico-Biological Interactions, 2017
    Co-Authors: Linh Thuy Nguyen, Kateřina Lněnickova, Martin Ambrož, Pavel Anzenbacher, Zuzana Mysliveckova, Barbora Szotakova, Alena Spicakova, Vladimir Kubicek, Kristýna Krasulova, Lenka Skalova
    Abstract:

    Abstract Sesquiterpenes, the main components of plant essential oils, are often taken in the form of folk medicines and dietary supplements. Several sesquiterpenes possess interesting biological activities but they could interact with concurrently administered drugs via inhibition of drug-metabolizing enzymes. Therefore, the present study was designed to test the potential inhibitory effect of tree structurally relative sesquiterpenes β-Caryophyllene (CAR), β-Caryophyllene Oxide (CAO) and α-humulene (HUM) on the activities of the main drug-metabolizing enzymes. For this purpose, rat and human hepatic subcellular fractions were incubated with CAR, CAO or HUM together with specific substrates for oxidation, reduction and conjugation enzymes and their coenzymes. HPLC, spectrophotometric and spectrofluorimetric analyses of product formations were used. All tested sesquiterpenes significantly inhibited cytochromes P4503A (CYP3A) activities in rats as well as in human hepatic microsomes, with CAO being the strongest inhibitor. A non-competitive type of inhibition was found. On the other hand, none of the tested sesquiterpenes significantly affected the activities of carbonyl-reducing enzymes (CBR1, AKRs, NQO1) or conjugation enzymes (UGTs, GSTs, SULTs, COMT). As CYP3A enzymes metabolize many drugs, their inhibition by CAO, CAR and HUM might affect the pharmacokinetics of concurrently administered drugs. Similar results obtained in rat and human hepatic microsomes indicate that rats could be used for further testing of possible drug-sesquiterpenes interactions in vivo.

  • the effects of β Caryophyllene Oxide and trans nerolidol on the efficacy of doxorubicin in breast cancer cells and breast tumor bearing mice
    Biomedicine & Pharmacotherapy, 2017
    Co-Authors: Veronika Hanusova, Hana Svobodova, Martin Ambrož, Kateřina Caltova, Adam Skarka, Natalie Murinova, Věra Kralova, Pavel Tomsik, Lenka Skalova
    Abstract:

    Abstract Background One approach to improve effect of chemotherapy is combination of classical cytostatic drugs with natural compounds, e. g. sesquiterpenes. In our previous study, sesquiterpenes β-Caryophyllene Oxide (CAO) and trans-nerolidol (NER) improved the anti-proliferative effect of doxorubicin (DOX) in intestinal cancer cell lines. Purpose The present study was designed to evaluate the effect of CAO and NER on DOX efficacy, focusing on cell proliferation, migration, apoptosis and DOX accumulation in breast cancer cells MDA-MB-231 and MCF7 in vitro and in mice bearing solid Ehrlich tumors (EST) in vivo. Methods The impact of cytotoxic effect was assessed by the neutral red uptake test. The ability to migrate was tested using real-time measurement in x-CELLigence system. Expressions of molecules were examined using western blot analysis. The accumulation of DOX inside the cells using time lapse microscopy was observed. The mice with inoculated EST cells were treated repeatedly with DOX and DOX + CAO or DOX + NER and the growth of tumors were monitored. DOX concentrations in plasma and tumor were assayed using HPLC. Results In MDA-MB-231, combination of DOX with CAO enhanced anti-proliferative effect and acted strongly synergistic. NER increased accumulation of DOX inside the cells; moreover combination DOX with NER suppressed migration ability in vitro. In vivo, apoptosis was activated especially in group treated with DOX and CAO. However, none of tested sesquiterpenes was able to improve DOX accumulation in tumors and DOX-mediated inhibition of tumor growth. Conclusion In conclusion, sesquiterpenes CAO and NER increased the efficacy of DOX in breast cancer cells in vitro, but did not improve its effect in vivo, in Ehrlich solid tumor bearing mice.