Martina Höferl

Correlation of Antimicrobial Activities of Various Essential Oils and Their Main Aromatic Volatile Constituents

Abstract The pure aromatic volatiles p-cymene, carvacrol, eugenol and thymol as well as commercial essential oils of Cinnamomum zeylanicum, Origanum vulgare, Pimenta dioica, Pimenta racemosa, Satureja hortensis, Syzygium aromaticum, Thymus vulgaris and Trachyspermum ammi were investigated concerning antimicrobial activities. Therefore, these samples and, as reference substances, synthetic antibiotics and the natural antimicrobial components carveol, m-, o- and p-cresol were tested against strains of two Gram-positive and five Gram-negative bacteria and the yeast Candida albicans using agar dilution and agar diffusion methods. The analysis of the chemical composition of the essential oils by means of GC and GC/MS focusing on aromatic volatiles produced the following results: C. zeylanicum: eugenol (74.9%); O. vulgare: carvacrol (66.1%) and p-cymene (9.2%); P. dioica: eugenol (76.0%); P. racemosa: eugenol (45.6%); S. hortensis: carvacrol (41.5%), p-cymene (10.7%) and thymol (8.7%); S. aromaticum: eugenol (76.8%); T. vulgaris: thymol (43.4%), p-cymene (23.5%) and carvacrol (4.1%); T. ammi: thymol (43.7%) and p-cymene (17.7%). All investigated aromatic volatiles and essential oils exhibited strong effects against the yeast Candida albicans and medium to strong antimicrobial activity against the Gram-positive bacteria Staphylococcus aureus and Enterococcus faecalis and the Gram-negative bacteria Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, and Salmonella sp., whereas weaker effects were observed against Pseudomonas aeruginosa.

Chemical Composition and Antioxidant Properties of Juniper Berry (Juniperus communis L.) Essential Oil. Action of the Essential Oil on the Antioxidant Protection of Saccharomyces cerevisiae Model Organism

The essential oil of juniper berries (Juniperus communis L., Cupressaceae) is traditionally used for medicinal and flavoring purposes. As elucidated by gas chromatography/flame ionization detector (GC/FID) and gas chromatography/mass spectrometry (GC/MS methods), the juniper berry oil from Bulgaria is largely comprised of monoterpene hydrocarbons such as α-pinene (51.4%), myrcene (8.3%), sabinene (5.8%), limonene (5.1%) and β-pinene (5.0%). The antioxidant capacity of the essential oil was evaluated in vitro by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging, 2,2-azino-bis-3-ethylbenzothiazoline-6 sulfonic acid (ABTS) radical cation scavenging, hydroxyl radical (ОН•) scavenging and chelating capacity, superoxide radical (•O2−) scavenging and xanthine oxidase inhibitory effects, hydrogen peroxide scavenging. The antioxidant activity of the oil attributable to electron transfer made juniper berry essential oil a strong antioxidant, whereas the antioxidant activity attributable to hydrogen atom transfer was lower. Lipid peroxidation inhibition by the essential oil in both stages, i.e., hydroperoxide formation and malondialdehyde formation, was less efficient than the inhibition by butylated hydroxytoluene (BHT). In vivo studies confirmed these effects of the oil which created the possibility of blocking the oxidation processes in yeast cells by increasing activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx).

In Silico Predictions of Drug – Drug Interactions Caused by CYP1A2, 2C9 and 3A4 Inhibition – a Comparative Study of Virtual Screening Performance

The cytochrome P450 (CYP) superfamily represents the major enzyme class responsible for the metabolism of exogenous compounds. Investigation of clearance pathways is therefore an integral part in early drug development, as any alteration of metabolic enzymes may markedly influence the toxicological profile and efficacy of novel compounds. In silico methods are widely applied in drug development to complement experimental approaches. Several different tools are available for that purpose, however, for CYP enzymes they have only been applied retrospectively so far. Within this study, pharmacophore‐ and shape‐based models and a docking protocol were generated for the prediction of CYP1A2, 2C9, and 3A4 inhibition. All theoretically validated models, the validated docking workflow, and additional external bioactivity profiling tools were applied independently and in parallel to predict the CYP inhibition of 29 compounds from synthetic and natural origin. After subsequent experimental assessment of the in silico predictions, we analyzed and compared the prospective performance of all methods, thereby defining the suitability of the applied techniques for CYP enzymes. We observed quite substantial differences in the performances of the applied tools, suggesting that the rational selection of that virtual screening method that proved to perform best can largely improve the success rates when it comes to CYP inhibition prediction.

Chemical composition and antimicrobial activity of essential oil of Algerian Tetraclinis articulata (Vahl) Masters

Abstract This study evaluates the chemical composition and antimicrobial activity of essential oils of Tetraclinis articulata (Vahl) Masters from Algeria. The essential oils of fresh and dried leaves were analyzed by GC-FID and GC-MS, identifying sixty-two and fifty-four volatile compounds representing 88% and 98% of the total essential oil composition, respectively. The main compounds of T. articulata essential leaf oils were α-pinene (36.1% in fresh, 44.1% in dried leaves), camphor (1.7%/20.1%), bornyl acetate (18.3%/3.1%), limonene (2.9%/5.0%), borneol (2.3%/3.1%), myrcene (2.2%/2.9%), β-caryophyllene (2.3%/1.3%) and camphene (1.5%/1.8%). The antimicrobial activity of T. articulata essential oils were tested against clinical isolates of Staphylococcus aureus, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas aeruginosa and Candida albicans, responsible for nosocomial infections. Essential oils of T. articulata were active on all pathogenic strains tested.

Interplay of drug metabolizing enzymes with cellular transporters

SummaryMany endogenous and xenobiotic substances and their metabolites are substrates for drug metabolizing enzymes and cellular transporters. These proteins may not only contribute to bioavailability of molecules but also to uptake into organs and, consequently, to overall elimination. The coordinated action of uptake transporters, metabolizing enzymes, and efflux pumps, therefore, is a precondition for detoxification and elimination of drugs. As the understanding of the underlying mechanisms is important to predict alterations in drug disposal, adverse drug reactions and, finally, drug–drug interactions, this review illustrates the interplay between selected uptake/efflux transporters and phase I/II metabolizing enzymes.ZusammenfassungViele endogene Substanzen und Xenobiotika und ihre Metaboliten sind Substrate für arzneistoffmetabolisierende Enzyme und zelluläre Transporter. Diese Proteine beeinflussen nicht nur die Bioverfügbarkeit, sondern auch deren Aufnahme in Organe, die Plasmakonzentration sowie die Ausscheidung. Das koordinierte Zusammenspiel von Aufnahmetransportern, arzneistoffmetabolisierenden Enzymen und Effluxpumpen ist eine Voraussetzung für Entgiftung und Ausscheidung von Arzneistoffen. Das Verständnis der zugrundeliegenden Mechanismen ist essentiell, um Elimination, Nebenwirkungen und letztendlich Wechselwirkungen vorherzusagen. Daher soll in dieser Übersichtsarbeit das Zusammenspiel am Beispiel von ausgewählten Aufnahme/Effluxtransportern mit Phase I/II Enzyme veranschaulicht werden.

The effect of the molecular adsorbent recirculating system on moxifloxacin and meropenem plasma levels.

Adequate plasma antibiotic concentrations are necessary for effective elimination of invading microorganism; however, extracorporeal organ support systems are well known to alter plasma concentrations of antibiotics, requiring dose adjustments to achieve effective minimal inhibitory concentrations in the patients blood.

Chemical Composition of the Essential Oil of Zanthoxylum avicennae (Lam.) DC Leaves (Rutaceae) from Vietnam

Abstract The volatile components of the essential leaf oil of Zanthoxylum avicennae (Lam.) DC (Rutaceae) from Nghean province (Vietnam) were analyzed by means of capillary GC and GC-MS as well as in some cases by background subtraction of co-eluting compounds. Out of more than fifty identified compounds, the sesquiterpene hydrocarbons β-caryophyllene (17.01 %) and α-humulene (10.38 %) as well as the monoterpene hydrocarbons α-pinene (10.07 %) and β-phellandrene, were determined to be the major individual constituents of the essential oil. Further mono- and sesquiterpene hydrocarbons, such as α-terpinene, (E)-β-ocimene, λ-terpinene, germacrene D and β-selinene, were found in concentrations higher than 3.0 %.

Lack of dermal penetration of topically applied gentamicin as pharmacokinetic evidence indicating insufficient efficacy

Background Treatment of skin and superficial soft tissue infections with topically applied antibiotics is a controversial topic, because only few clinical studies exist and target site concentrations after topical treatment are widely unknown. Objectives This study aimed to investigate the target site concentration of topically applied gentamicin as a potential cause of therapeutic failure and to explore if microporation by laser might be used to improve penetration of gentamicin through the skin barrier. Methods Six healthy volunteers were included in this cross-over Phase 1 study. On two study days, separated by a washout period, microdialysate and plasma sampling was performed for 6 h after administration of 500 mg of gentamicin cream on a predefined area. On one of the study days the skin was microporated before drug application using the P.L.E.A.S.E. Professional laser system. Results In intact skin, Cmax and AUC values were 3.3 ± 5.64 ng/mL and 5.4 ± 10.4 ng·h/mL, respectively; thereby far under the threshold needed to treat common pathogens. With a Cmax of 474.2 ± 555.3 ng/mL laser application showed a significant increase in tissue penetration and decrease in pharmacokinetic variability; however, even after microporation no therapeutically active concentrations were achieved as indicated by Cmax/epidemiological cut-off ratios of 0.237 and 0.059 for Staphylococcus aureus and Pseudomonas aeruginosa, respectively. Solely after administration on microporated skin, plasma concentrations of gentamicin were quantifiable (lower limit of quantification 10 pg/mL). Conclusions This study confirmed that after topical administration gentamicin penetration through the dermal barrier is insufficient, providing pharmacokinetic evidence that topical gentamicin in its current form might be inappropriate to treat skin infections.

Antimicrobial activities of various essential oils and their main aromatic volatile constituents

The pure aromatic volatiles p-cymene, carvacrol, eugenol and thymol as well as commercial essential oils oiCinnamomum zeijlanicum. Origanum vulgäre, Pinienta dioica. Pimenta racemosa. Satureja hortensis, Stjztjgium aroinaticum. Thymus vulgaris and Trachyspemium ammi were investigated concerning antimicrobial activities. Therefore, these samples and, as reference substances, synthetic antibiotics and the natural antimicrobial components carveol, m-, oand p-cresol were tested against strains of two Gram-positive and five Gram-negative bacteria and the yeast Candida alhicans using agar dilution and agar diffusion methods. The analysis ofthe chemical composition ofthe essential oils by means of GC and GG/MS focusing on aromatic volatiles produced the following results: C. zeijlanicum: eugenol (74.9%); O. vulgäre: carvacrol (66.1%) and p-cymene (9.2%); P dioica: eugenol (76.0%); P. racenwsa: eugenol (45.6%); S. hortensis: carvacrol (41.5%), p-cymene (10.7%) and thymol (8.7%); S. aronmtioum: eugenol (76.8%); T. vulgaris: thymol (43.4%), p-cymene (23.5%) and carvacrol (4.1%); T. ammi: thymol (43.7%) and p-cymene (17.7%). All investigated aromatic volatiles and essential oils exhibited strong effects against the yeast Candida albicans and medium to strong antimicrobial activity against the Gram-positive bacteria Staphylococcus aureus and Enterococcus faecalis and the Gram-negative bacteria Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, and Salnwnella sp., whereas weaker effects were observed against Pseudomonas aeruginosa.