caryophyllene-oxide and nerolidol

Sesquiterpenes, the main components of plant essential oils, are bioactive compounds with numerous health-beneficial activities. Sesquiterpenes can interact with concomitantly administered drugs due to the modulation of drug-metabolizing enzymes (DMEs). The aim of this study was to evaluate the modulatory effects of six sesquiterpenes (farnesol,

Topics: Aged; Aged, 80 and over; Aldo-Keto Reductases; Carbonyl Reductase (NADPH); Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 2; Farnesol; Female; Hep G2 Cells; Hepatocytes; Humans; Liver; Male; Metabolic Clearance Rate; Middle Aged; Monocyclic Sesquiterpenes; Polycyclic Sesquiterpenes; Pregnane X Receptor; Receptors, Aryl Hydrocarbon; RNA, Messenger; Sesquiterpenes

Evaluation of possible interactions with enzymes of drug metabolism is an important part of studies on safety and, in general, on the properties of any drug or biologically active compound. Here, focus is given on interactions of three sesquiterpenes (beta-caryophyllene oxide (CAO), trans-nerolidol (tNER) and farnesol (FAR)) with CYP3A4. To determine the CYP3A4 activity, specific substrates testosterone (TES) and midazolam (MDZ) were used. In human liver microsomes, the CAO inhibited the MDZ 1´-hydroxylation by mixed type inhibition and K(i) 46.6 microM; TES 6beta-hydroxylation was inhibited more strongly by tNER by the same mechanism and with K(i) of 32.5 microM. Results indicated a possibility of different mode of interaction of both compounds within the active site of CYP3A4 and this was why the molecular docking study was done. The docking experiments showed that the studied sesquiterpenes (CAO and tNER) bound to the CYP3A4 active site cause a significant decrease of binding affinity of substrates tested which corresponded well to the inhibition studies. The inhibition observed, however, most probably does not pose a real harm to microsomal drug metabolism as the levels of sesquiterpenes in plasma (assuming the use of these compounds as spices or flavoring additives) does not usually exceed micromolar range. Hence, the interaction of drugs metabolized by CYP3A4 with sesquiterpenes is less probable.

Topics: Catalytic Domain; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Farnesol; Humans; Microsomes, Liver; Models, Molecular; Molecular Docking Simulation; Molecular Structure; Polycyclic Sesquiterpenes; Sesquiterpenes

The present study is designed to find out if sesquiterpenes, α-humulene (HUM), valencene (VAL), β-caryphyllene-oxide (CAO) and trans-nerolidol (NER), are able to improve the antiproliferative effect of classical cytostatic drugs, 5-fluorouracil (FU) and oxaliplatin (1,2-diaminocyclohexaneoxalato-platinum, OxPt), in colon cancer cell lines Caco-2 and SW-620. In addition, the possible mechanisms of sesquiterpene action are studied. The results show significant ability of HUM and especially of CAO to enhance the anti-proliferative effects of FU and OxPt in cancer cell lines Caco-2 and SW-620. On the other hand, VAL and NER are ineffective. The action of CAO could be partly based on its ability to disrupt the mitochondrial membrane potential and to activate initiator caspases, but other mechanisms are probably also involved. Based on these results, CAO seems to have the potential for combination therapy of colon cancers and deserves further study.

Topics: Caco-2 Cells; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Fluorouracil; Humans; Membrane Potential, Mitochondrial; Monocyclic Sesquiterpenes; Oxaliplatin; Polycyclic Sesquiterpenes; Sesquiterpenes

Micromeria persica Boiss. is medicinal and aromatic plant, belonging to the Lamiaceae family. The chemical composition of the essential oils (EOs) from aerial parts of M. persica were extracted using hydro-distillation method and analysed using GC and GC-MS. Fifty-two compounds were identified in the EOs of aerial parts of M. persica. The main chemical compositions were n-hexadecanoic acid (14.9%), thymol (9.5%), linoleic acid (8.0%), carvacrol (5.6%), (E)-nerolidol (5.5%), linolenic acid (5.5%), α-cadinol (2.7%), linalool (2.7%), borneol (2.6%), caryophyllene oxide (2.3%) and pulegone (2.0%). Presence of borneol, thymol, carvacrol and pulegone suggests the potential of this plant as a flavouring source in the food industry, being used in perfumery and cosmetics industry, vitamin E synthesis and exhibit strong fungicidal, antibacterial and antimicrobial activities.

Topics: Acyclic Monoterpenes; Camphanes; Cyclohexane Monoterpenes; Cymenes; Gas Chromatography-Mass Spectrometry; Iran; Lamiaceae; Monoterpenes; Oils, Volatile; Plant Components, Aerial; Polycyclic Sesquiterpenes; Sesquiterpenes; Terpenes; Thymol

1. 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 of sesquiterpenes modulate activities and expression of several xenobiotic-metabolizing enzymes.

Topics: Aldehyde Reductase; Animals; Cytochrome P-450 Enzyme System; Enzymes; Estradiol Dehydrogenases; Gene Expression Regulation, Enzymologic; Inactivation, Metabolic; Intestine, Small; Liver; Male; Mice, Inbred Strains; NAD(P)H Dehydrogenase (Quinone); Polycyclic Sesquiterpenes; Sesquiterpenes

Topics: Cell Line, Tumor; Cell Proliferation; Cell Survival; Doxorubicin; Drug Resistance, Multiple; Drug Synergism; Drug Therapy, Combination; Humans; Monocyclic Sesquiterpenes; Myrica; Oils, Volatile; Polycyclic Sesquiterpenes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sesquiterpenes

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.. 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.. 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.. 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.. 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.

Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Doxorubicin; Female; Humans; Inhibitory Concentration 50; Mammary Neoplasms, Animal; Mice; Polycyclic Sesquiterpenes; Sesquiterpenes; Treatment Outcome

The chemical composition and antimicrobial activity studies on the essential oils of Hypericum rochelii Griseb. & Schenk and Hypericum umbellatum A. Kern. have been carried out for the first time. Seventy-nine compounds were identified in the essential oil of H. rochelii with n-nonane (24.7%), β-pinene (22.4%), germacrene D (7.5%), n-undecane (6.8%) and α-pinene (5.8%) as main constituents. One hundred and twenty-six compounds were identified in H. umbellatum essential oil with germacrene D (6.1%), (E)-nerolidol (4.4%), n-nonane (4.0%), (E)-caryophyllene (3.0%) and caryophyllene oxide (3.0%) as the most abundant components. Both oils were characterized by the presence of many components which could have numerous applications in food, pharmaceutical and perfume industries. Taxa studied herein belong to the section Drosocarpium Spach, and their intrasectional placement based on the essential oil profiles was discussed. The oils were tested in a broth microdilution assay against five bacterial and two fungal strains and found to have mainly moderate antimicrobial effects.

Topics: Alkanes; Anti-Infective Agents; Bicyclic Monoterpenes; Bridged Bicyclo Compounds; Hypericum; Monoterpenes; Oils, Volatile; Plant Extracts; Polycyclic Sesquiterpenes; Sesquiterpenes; Sesquiterpenes, Germacrane

The essential oils isolated at the flowering stage in spring, summer and autumn of the aerial and underground parts of Conyza bonariensis L. growing in Tunisia were analysed by GC and GC/MS; 143 constituents were identified, and among them 20 were major. The oils of C. bonariensis gathered in spring were rich in matricaria ester (1.2-67.3%), (Z)-nerolidol (0.3-19.9%) and caryophyllene oxide (0.8-14.3%). In the summer samples, the oils of C. bonariensis were rich in matricaria ester (1.6-76.4%), caryophyllene oxide (1.6-22.6%) and (E)-β-farnesene (1.1-22.7%). The main constituents in the autumn samples were matricaria ester (trace to 63.5%), geranyl acetone (0.0-25.3%), trans-α-bergamotene (0.0-24.3%) and limonene (2.7-15.3%). The oils showed significant variation among the seasons. Remarkable differences were found between the constituent percentages of the different studied organs. The C. bonariensis sample from Tunisia was a matricaria ester chemotype and was quite different from the samples of other countries of origin.

Topics: Bridged Bicyclo Compounds; Conyza; Cyclohexenes; Diynes; Gas Chromatography-Mass Spectrometry; Limonene; Oils, Volatile; Plant Components, Aerial; Plant Roots; Polycyclic Sesquiterpenes; Seasons; Sesquiterpenes; Terpenes; Tunisia