Beta-caryophyllene Oxide Research Articles

GC-MS/FID analysis, antibacterial activity and modes of action of essential oils from three Aframomum species found in Cameroon against foodborne pathogenic bacteria

Background: The current study examined the chemical profile and in vitro antibacterial activity of essential oils (EOs) extracted from Aframomum danielli (leaves and seeds), Aframomum chlamydentum (leaves), and Aframomum melegueta (leaves) against foodborne pathogenic bacteria.
 Methods: The hydro-distillation technique using a Clevenger-type apparatus was used to extract EOs, whereas the Gas Chromatography-Mass Spectrometry (GC-MS) and GC coupled to Flame Ionization Detector (GC-FID) allowed the chemical characterization of oil constituents. The broth micro-dilution method was applied for the determination of the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Besides, some modes of action were studied on the cell membrane integrity and biofilm formation of Salmonella typhi.
 Results: The major compounds identified from EOs of A. danielli seeds were eucalyptol (48.707%), limonene (11.368%), beta pinene (10.342-10.335%), and alpha terpineol (8.785-9.049%), whereas EOs from A. danielli leaves were dominated by sabinene (42.87%), beta pinene, (11.22%), caryophyllene (7.84%), terpinen-4-ol (5.68%), linalool (3.48%) and gamma terpinene (2.02%). Major volatile markers from EOs of A. chlamydentum leaves comprised beta pinene (49.72%), caryophyllene (10.62%), alpha pinene (6.21%) and linalool (2.96%), while those of EOs from A. melegueta included beta pinene (37.15%), caryophyllene (17.64%), caryophyllene oxide (8.72%) and alpha pinene (8.26%). This study is the first to report on the chemical constituents of EOs from A. chlamydentum. Test oils displayed significant antibacterial activity with the MIC ranging from 0.0625 to 0.5% (v/v). EOs from A. melegueta (leaves) appeared to be the most active, acting against all tested bacteria. All EOs identified displayed bactericidal effects against Citrobacter freundii, a bacterium known to cause a broad range of infections associated with a higher rate of in-hospital mortality. The EOs from A. melegueta may act through perturbation of cell membrane integrity and permeability as well as the inhibition of bacterial biofilm formation.
 Conclusion: Our findings suggest the possible application of essential oils in agricultural food products for the control of bacterial diseases.

Insecticidal Activity of Powder and Essential Oils of Vepris heterophylla (Rutaceae) and Syzygium aromaticum (Mytaceae) Towards Callosobruchus maculatus F. walp (Coleoptera: Bruchidae) on Post-Harvest Vigna unguiculata (Fabaceae) in the Far-North Region of Cameroon

The bioinsecticidal effect of powders and essential oils of S. aromaticum (L.) flower buds and V. heterophylla (Engl.) leaves against adult cowpea weevil C. maculatus was studied. Powders were tested by direct contact only while essential oils were tested by direct contact and indirect contact (inhalation and repellency). In 500 mL glass jars, the individual and combined powders were applied to 100 g of cowpea seeds at 0.5 g, 1 g, 1.5 g and 2 g doses for both leaves and flower buds of V. heterophylla and S. aromaticum respectively. The essential oils were also applied individually and after equilibrium combination on 50 g of cowpea at 4 µL/mL, 8 µL/mL, 12 µL/mL, 16 µL/mL. All the infestations were then achieved by adding 20 bruchids of 48 h old. The essential oil obtained was purified and analyzed with Gas Chromatography and Mass Spectrometry (GC-MS). 72 h after the individual treatment, 100% mortality was obtained at 2 g dose for V. heterophylla and 0.5 g dose for S. aromaticum compared to the control jars (1%). The combined powders were found to be more effective with 100% of mortality at a dose 1 g after 48 h of exposure. For essential oils, 100% and 90% of mortality were obtained respectively at 8 µL/mL dose for S. aromaticum (160 µL/kg) and 16 µL/mL dose for V. heterophylla (320 µL/kg) 72 h after treatment. In addition, the essential oil of S. aromaticum showed relatively higher repellant properties with an average repellency percentage of PR = 89.37% than that of V. heterophylla (PR = 70.62%). 100% of mortality was induced after inhalation of essential oils of S. aromaticum and V. heterophylla at doses 10 µL and 40 µL respectively after 72 h of exposure time. The results obtained from the GC-MS showed that the major components in the essential oil of S. aromaticum were eugenol (83.40%) although that of V. heterophylla were Spathulenol (23.66%), Beta-Caryophyllene oxide (16.46%) and 6-Isopropenyl-4 (16.30%). The powders and essential oils of the tested plants applied individually or after equilibrium combination showed interesting prospects for controlling Callosobruchus maculatus and effectively preserving cowpea seeds in storage warehouses.

Beta-caryophyllene oxide and trans-nerolidol affect enzyme activity of CYP3A4 - in vitro and in silico studies.

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.

The sesquiterpene beta-caryophyllene oxide attenuates ethanol drinking and place conditioning in mice

Approximately 20 million adults in the United States have an alcohol use disorder. In recent years, modulation of the behavioral effects of ethanol by phytochemicals has been explored. In this study, we used the ethanol-induced loss of righting reflex (LORR) assay to assess potency differences between the sesquiterpene phytochemical beta-caryophyllene (BCP) and its derivative caryophyllene oxide (BCPO). We also investigated the effects of BCPO on two bottle-choice ethanol drinking and the ethanol-induced conditioned place preference (CPP). We then determined whether there are any pharmacokinetic or pharmacodynamic interactions between BCPO and ethanol, using blood ethanol analysis and pretreatments with the selective cannabinoid receptor 2 (CB2) antagonist AM630, respectively. BCPO augmented the ethanol-induced LORR at a dose (30 mg/kg) tenfold lower than BCP (300 mg/kg). Swiss-Webster mice were found to split into stable high and low drinking groups. This same dose (30 mg/kg) of BCPO significantly decreased ethanol intake and preference for ethanol over water in mice that consumed high amounts of ethanol, without any effect on total fluid intake. BCPO had limited effects in mice that consumed low amounts of ethanol. BCPO also significantly attenuated the ethanol-induced CPP. Blood ethanol analysis showed no significant effect of ethanol on the pharmacokinetics of ethanol. Furthermore, the enhancement of the ethanol-induced LORR by BCPO was reversed by AM630. These findings demonstrate that BCPO more potently modulates the behavioral effects of ethanol than the parent compound BCP. Moreover, they suggest that BCPO modulates the behavioral effects of ethanol through pharmacodynamic rather than pharmacokinetic mechanisms.

SAT-169 - Chemosensitizing effects of beta-caryophyllene oxide in liver cancer

SAT-169 - Chemosensitizing effects of beta-caryophyllene oxide in liver cancer

Beta Caryophyllene and Caryophyllene Oxide, Isolated from Aegle Marmelos, as the Potent Anti-inflammatory Agents against Lymphoma and Neuroblastoma Cells

Aegle marmelos (Indian Bael) is a tree which belongs to the family of Rutaceae. It holds a prominent position in both Indian medicine and Indian culture. We have screened various fractions of Aegle marmelos extracts for their anticancer properties using in vitro cell models. Gas chromatography-Mass spectrometry (GC-MS) was employed to analyze the biomolecules present in the Aegle marmelos extract. Jurkat and human neuroblastoma (IMR-32) cells were treated with different concentrations of the fractionated Aegle marmelos extracts. Flow cytometric analysis revealed that optimal concentration (50 µg/ml) of beta caryophyllene and caryophyllene oxide fractions of Aegle marmelos extract can induce apoptosis in Jurkat cell line. cDNA expression profiling of pro-apoptotic and anti-apoptotic genes was carried out using real time PCR (RT-PCR). Down-regulation of anti-apoptotic genes (bcl-2, mdm2, cox2 and cmyb) and up-regulation of pro-apoptotic genes (bax, bak1, caspase-8, caspase-9 and ATM) in Jurkat and IMR-32 cells treated with the beta caryophyllene and caryophyllene oxide fractions of Aegle marmelos extract revealed the insights of the downstream apoptotic mechanism. Furthermore, in-silico approach was employed to understand the upstream target involved in the induction of apoptosis by the beta caryophyllene and caryophyllene oxide fractions of Aegle marmelos extract. Herein, we report that beta caryophyllene and caryophyllene oxide isolated from Aegle marmelos can act as potent anti-inflammatory agents and modulators of a newly established therapeutic target, 15-lipoxygenase (15-LOX). Beta caryophyllene and caryophyllene oxide can induce apoptosis in lymphoma and neuroblastoma cells via modulation of 15-LOX (up-stream target) followed by the down-regulation of anti-apoptotic and up-regulation of pro-apoptotic genes.

Chemical composition and biological activity of the essential oil obtained from <I>Bupleurum marginatum</I> (Apiaceae)

Bupleurum marginatum is a herb indigenous to the southern and southwestern part of China. It is widely used in many Chinese prescriptions. We aimed to investigate the chemical composition, antioxidant, anti-inflammatory, antimicrobial and in-vitro cytotoxic activity of the hydrodistilled and extracted essential oil from B. marginatum to validate some of its ethnopharmacologial uses. The essential oil of the aerial parts of B. marginatum was analysed by capillary gas chromatography (GLC/FID) and gas chromatography-mass spectrometry (GLC/MS). The ability of the oil to reduce diphenylpicrylhydrazine (DPPH(.)) and to prevent the degradation of deoxyribose were used to evaluate the antioxidant activity. Inhibition of both prostaglandin E(2) production and lipoxygenase were used to assess the anti-inflammatory activity. Antimicrobial activity was studied in vitro against a range of bacteria and fungi. The in-vitro cytotoxicity of the essential oil on six human cancer cell lines (HepG2, Caco-2, CCRF-CEM, HeLa, MiaPaCa-2 and MCF-7) was examined using the MTT assay. Seventy-two components, comprising almost 94.29% of the total peak area, were identified in the analysis. The main components were tridecane (13.18%), undecane (10.42%), pentadecane (8.71%), beta-caryophyllene (5.53%) and beta-caryophyllene oxide (5.29%). The ability of the oil to reduce diphenylpicrylhydrazine (DPPH(.)) and to prevent the degradation of deoxyribose were used to evaluate the antioxidant activity and the corresponding IC50 values (drug concentration which resulted in a 50% reduction in inhibition of the activity) were found to be 3.66 mg/ml and 17.4 microg/ml, respectively. Inhibition of both prostaglandin E(2) production and lipoxygenase were used to assess the anti-inflammatory activity (IC50 of 63.64 microg/ml for lipoxygenase, 26.04% inhibition of prostaglandin E(2) at 25 microg/ml dose). The oil also showed a significant in-vitro antimicrobial activity against Gram positive pathogens (Streptococcus pyogenes and Streptococcus agalactiae) with minimum inhibitory concentration (MIC) values ranging from 0.125 up to 4.00 mg/ml. The in-vitro cytotoxicity of the essential oil on six human cancer cell lines (HepG2, Caco-2, CCRF-CEM, HeLa, MiaPaCa-2 and MCF-7) examined using the MTT assay revealed the highest activity to be in the CCRF-CEM cell line with an IC50 (concentration which resulted in a 50% reduction in cell viability) of 46.01 microg/ml after 24 h treatment. The essential oil of B. marginatum exhibited a promising anti-inflammatory activity along with strong cytotoxicity against many cancer cells (CCRF-CEM and HepG2) mediated through induction of apoptosis, and this in-vitro activity make its local traditional uses rational. However, its limited antimicrobial activity indicates that a combination with other drugs is essential for effective use. Further selectivity testing is required to evaluate the effect of the oil against normal cells.

Di- and sesqui-terpenoids isolated from the pods ofSindora sumatrana and their potential to inhibit lipopolysaccharide-induced nitric oxide production

Activity-guided fractionation of the n-hexane and CHCl3-soluble fractions of Sindora sumatrana using a bioassay based on the inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production by inducible nitric oxide synthase (iNOS) in murine macrophage RAW 264.7 cells led to the isolation of the known compound, (+)-7beta-acetoxy-15,16-epoxy-3,13(16),14-clerodatriene-18-oic acid (2) as an active constituent. In addition, a new trans-clerodane diterpenoid, (+)-2-oxokolavenic acid (1), together with six known compounds, (+)-3,13-clerodadiene-16,15-olide-18-oic acid (3), (+)-7beta-acetoxy-3,13-clerodadiene-16,15-olide-18-oic acid (4), (+)-7beta-acetoxy-16-hydroxy-3,13-clerodadiene-16,15-olide-18-oic acid (5), beta-caryophyllene oxide (6), clovane-2beta,9beta-diol (7), and caryolane-1,9beta-diol (8) were isolated and found to be inactive. The structure of compound 1 was determined using physical and spectroscopic methods such as 1D and 2D-NMR experiments. The known compounds 2-8 were identified by the spectroscopic data and by comparison with the published values. Of eight isolates (1-8), only compound 2 exhibited an iNOS inhibitory activity with IC50 value of 51.6 microM.

The Influence of the Harvest Cut Height on the Quality of the Herbal Drugs Melissae folium and Melissae herba

Variability in both the content and quality of essential oil was observed in herb and leaf drugs in dependence on the harvest cut height of lemon balm (Melissa officinalis L. cv. Citra). Three different cuts were carried out on the respective plants. The oil content in the herb was highest in the top third (0.13 % V/m), satisfactory in the herb including both the top and middle thirds (0.08 % V/m) and lowest in the whole herb (0.06 % V/m). The oil content in the leaves of the respective herbs was in the range 0.39 % - 0.14 % V/m (top third part - whole aerial part). The percentage of citrals, linalool and beta-caryophyllene in essential oil decreased in the basipetal direction, whilst the amounts of beta-caryophyllene oxide and citronellal increased in the same direction. Citrals (A and B): 55.79 % in the top third part of the herb, 48.46 % in the whole herb, 59.74 % and 56.87 % in the leaves from that parts, respectively. Similarly, beta-caryophyllene: 5.01 %, 3.87 %, 6.97 %, 5.13 %; beta-caryophyllene oxide: 17.19 %, 24.07 %, 15.64 %, 17.82 %; citronellal: 2.73 %, 5.51 %, 2.82 %, 6.44 %.

Effects of inhibition of calcium and potassium currents in guinea-pig cardiac contraction: comparison of beta-caryophyllene oxide, eugenol, and nifedipine.

1. To investigate the effects of the clove oil constituents beta-caryophyllene oxide and eugenol on the heart muscle, experiments were performed on isolated papillary muscles and on ventricular myocytes of the guinea-pig. The results were compared with those obtained with the dihydropyridine, nifedipine. 2. All three substances exerted negative inotropic effects in heart muscle although with different potencies and different influences on the time course of the contraction curve. 3. They all reduced rested-state contractions (RSCs) in the presence of isoprenaline which are thought to be due to the Ca(2+) current (I(Ca)). 4. beta-Caryophyllene oxide, eugenol and nifedipine inhibited the I(Ca) in single cells from the guinea-pig ventricle in a concentration-dependent, reversible way, but with different potencies. 5. In addition to the I(Ca)-inhibiting effect, beta-caryophyllene oxide strongly inhibited and eugenol slightly inhibited the potassium current. 6. The action potential of papillary muscles at a 1 Hz contraction frequency was greatly shortened by nifedipine, slightly shortened by eugenol, but not changed by beta-caryophyllene oxide. 7. The inhibition of the potassium current by beta-caryophyllene oxide obviously prevents a shortening of the action potential due to the diminution of the I(Ca). Accordingly, the negative inotropic effect of beta-caryophyllene oxide is closely related to the inhibition of I(Ca). In contrast, eugenol and nifedipine, which shorten the action potential, exert stronger negative inotropic effects than expected from their influence on I(Ca). 8. The results show that the negative inotropic effect of a calcium channel blocker can be attenuated by an additional inhibition of potassium channels.

Sesquiterpenes from clove (Eugenia caryophyllata) as potential anticarcinogenic agents.

Bioassay-directed fractionation of clove terpenes from the plant Eugenia caryophyllata has led to the isolation of the following five active known compounds: beta-caryophyllene [1], beta-caryophyllene oxide [2], alpha-humulene [3], alpha-humulene epoxide I [4], and eugenol [5]. Their structures were determined on the basis of spectral analysis (hreims, 1H and 13C nmr). These compounds showed significant activity as inducers of the detoxifying enzyme glutathione S-transferase in the mouse liver and small intestine. The ability of natural anticarcinogens to induce detoxifying enzymes has been found to correlate with their activity in the inhibition of chemical carcinogenesis. Thus, these sesquiterpenes show promise as potential anticarcinogenic agents.

Composition of Essential Oils ofLaurus nobilis, L. nobilisVar.angustifoliaandLaurus azorica

The essential oils of Laurus nobilis, L. nobilis var. angustifolia and L. azorica were investigated by means of GLC, IR, PMR, CMR and GC-MS. The composition of the oils of the first two mentioned species was about the same with as main constituent 1,8-cineole, whereas the oil of L. azorica was different with low content of 1,8-cineole (10% vice 40-50%), absence of spathulenol, high content of alpha- and beta-pinene and presence of alpha-copaene, cinnamyl acetate, allo-aromadendrene, beta-eudesmol, beta-caryophyllene oxide and 1 (12), 8 (15)-caryophylladiene-9alpha-ol. About 50 components were tentatively identified.

Identification and Quantitative Analysis of the Volatile Substances Emitted by Maturing Cotton in the Field

When atmosphere from cotton plants (Gossypium hirsutum L., var. Deltapine Smoothleaf) was condensed by passing it over the expansion coil of an air conditioner and three 1-hour collections per day (early morning, noon, and late afternoon) were made, the total essential oils were found to consist of 50 to 60% beta-bisabolol (I(k) 1660) and gamma-bisabolene (I(k) 1550) and 30 to 40% geraniol (I(k) 1250), myrtenal (I(k) 1328), nerolidol (I(k) 1520), and beta-caryophyllene oxide (I(k) 1590). As the plant matured, trans-2-hexanol was produced in concentrations of 7 to 27%. Before fruiting, beta-bisabolol made up as much as 60% of the total essential oil transpired by the plants, and as the concentration of beta-bisabolol increased, that of gamma-bisabolene decreased.