OBJECTIVES: To develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify 41 different purine and pyrimidine (PuPy) metabolites in human urine to allow detection of most known disorders in this metabolic pathway and to determine reference intervals. METHODS: Urine samples were diluted with an aqueous buffer to minimize ion suppression. For detection and quantification, liquid chromatography was combined with electrospray ionization, tandem mass spectrometry and multiple reaction monitoring. Transitions and instrument settings were established to quantify 41 analytes and nine stable-isotope-labeled internal standards (IS). RESULTS: The established method is precise (intra-day CV: 1.4-6.3%; inter-day CV: 1.3-15.2%), accurate (95.2% external quality control results within ±2 SD and 99.0% within ±3 SD; analyte recoveries: 61-121%), sensitive and has a broad dynamic range to quantify normal and pathological metabolite concentrations within one run. All analytes except aminoimidazole ribonucleoside (AIr) are stable before, during and after sample preparation. Moreover, analytes are not affected by five cycles of freeze-thawing (variation: -5.6 to 7.4%), are stable in thymol (variation: -8.4 to 12.9%) and the lithogenic metabolites also in HCl conserved urine. Age-dependent reference intervals from 3,368 urine samples were determined and used to diagnose 11 new patients within 7 years (total performed tests: 4,206). CONCLUSIONS: The presented method and reference intervals enable the quantification of 41 metabolites and the potential diagnosis of up to 25 disorders of PuPy metabolism.
Origanum vulgare (O. Vulgare) is a medicinal and aromatic shrub. It is commonly used as a culinary spice and in "traditional medicine" to cure a variety of diseases. Almost all parts including roots, leaves, stems, and flowers, are employed in medical systems to treat a variety of ailments. In recent scientific literature, among other things, the plant was reported to behave clinical effectiveness against antibacterial, hyperglycemia, anthelminthic and antifungal actions. Carvacrol, limonene, thymol, ocimene, pinene, caryophyllene, terpenes-cymene, and other significant medicinal chemicals have been extracted from this genus through phytochemical studies. The phytochemical ingredients of O. vulgare are highlighted in this review and its traditional uses, as well as evidence-based studies on the plant's diverse pharmacological effects. This illustrates the importance of conducting a thorough investigation in order to report new information on the mechanisms of action of these impacts.
- MeSH
- Anti-Inflammatory Agents pharmacology therapeutic use MeSH
- Anti-Infective Agents pharmacology therapeutic use MeSH
- Antioxidants pharmacology therapeutic use MeSH
- Origanum * chemistry MeSH
- Pharmacologic Actions MeSH
- Phytochemicals chemistry pharmacology therapeutic use MeSH
- Antineoplastic Agents pharmacology therapeutic use MeSH
- Plant Extracts pharmacology therapeutic use MeSH
- Therapeutic Uses MeSH
The growing need for processing natural lipophilic and often volatile substances such as thymol, a promising candidate for topical treatment of intestinal mucosa, led us to the utilization of solid-state nuclear magnetic resonance (ss-NMR) spectroscopy for the rational design of enteric pellets with a thymol self-emulsifying system (SES). The SES (triacylglycerol, Labrasol®, and propylene glycol) provided a stable o/w emulsion with particle size between 1 and 7 μm. The ex vivo experiment confirmed the SES mucosal permeation and thymol delivery to enterocytes. Pellets W90 (MCC, Neusilin®US2, chitosan) were prepared using distilled water (90 g) by the M1-M3 extrusion/spheronisation methods varying in steps number and/or cumulative time. The pellets (705-740 μm) showed mostly comparable properties-zero friability, low intraparticular porosity (0-0.71%), and relatively high density (1.43-1.45%). They exhibited similar thymol release for 6 h (burst effect in 15th min ca. 60%), but its content increased (30-39.6 mg/g) with a shorter process time. The M3-W90 fluid-bed coated pellets (Eudragit®L) prevented undesirable thymol release in stomach conditions (<10% for 3 h). A detailed, ss-NMR investigation revealed structural differences across samples prepared by M1-M3 methods concerning system stability and internal interactions. The suggested formulation and methodology are promising for other lipophilic volatiles in treating intestinal diseases.
- Publication type
- Journal Article MeSH
Alveolar osteitis (AO) is a common complication following the extraction of the teeth, particularly the lower third molars. It starts within a few days after the extraction and manifests mainly as pain in the extraction site. Several strategies of treatment are available in order to relieve pain and heal the extraction wound. Recently, a novel medical device combining hyaluronic acid (HA) and octenidine (OCT) was introduced for the treatment of AO. This series of case reports aims to summarize the initial clinical experiences with this new device and to highlight factors possibly interfering with this treatment. The medical documentation of five patients with similar initial situations treated for AO with HA + OCT device was analyzed in detail. Smoking and previous treatment with Alveogyl (Septodont, Saint-Maur-des-Fossés, France) were identified as factors interfering with the AO treatment with the HA + OCT device. In three patients without these risk factors, the treatment led to recovery within two or three days. The patient pretreated with Alveogyl and the smoker required six and seven applications of the HA + OCT device, respectively. According to these initial observations, it seems smoking and previous treatment with Alveogyl prolong the treatment of AO using the HA + OCT device that, in turn, shows a rapid effect if these risk factors are not present.
- MeSH
- Pain drug therapy etiology physiopathology surgery MeSH
- Adult MeSH
- Tooth Extraction adverse effects MeSH
- Drug Combinations MeSH
- Wound Healing drug effects physiology MeSH
- Imines therapeutic use MeSH
- Hydrocarbons, Iodinated adverse effects MeSH
- Smoking adverse effects MeSH
- Creosote adverse effects MeSH
- Hyaluronic Acid therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Molar surgery MeSH
- Dry Socket drug therapy etiology physiopathology surgery MeSH
- Pyridines therapeutic use MeSH
- Risk Factors MeSH
- Thymol adverse effects MeSH
- Treatment Outcome MeSH
- Equipment and Supplies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
The increasing antibiotic resistance of microbial pathogens isolated from farm animals tissues and the environment has been the one of the most important challenges associated with the use of antibiotics. In order to achieve better production on a farm, animal feed is enriched with antibiotics often originally intended for therapeutic purposes, which may lead to notable increases in microbial resistance. One possible approach to decreasing the excessive use of antibiotics in livestock as well as antimicrobial resistance is utilizing the antimicrobial properties of natural substances. The aim of this study was to evaluate the antimicrobial activity of natural substances including carvacrol, thymol, eugenol, gallic acid, octyl gallate, cnicin and usnic acid against a wide spectrum of microorganisms. Cnicin was the only compound which was isolated from the plant with use of column chromatography. The antimicrobial activities of these natural substances were determined on the basis of their minimum inhibitory, minimum bactericidal and minimum fungicidal concentrations using the microdilution method. This determination of antimicrobial activity revealed thymol and cnicin to be effective natural substances against all tested microorganisms. Octyl gallate had a strong inhibitory and bactericidal effect against gram-positive bacteria and was the most effective against Candida strains. Usnic acid was shown to have the lowest minimum inhibitory concentrations for gram-positive bacteria. These results suggest the possible incorporation of natural substances in animal rearing in order to reduce the high amount of antibiotics which are not used directly to treat animal diseases.
- MeSH
- Drug Resistance, Microbial MeSH
- Antifungal Agents analysis MeSH
- Anti-Infective Agents * analysis MeSH
- Bacteria MeSH
- Candida MeSH
- Breeding MeSH
- Livestock * MeSH
- Indicator Dilution Techniques MeSH
- Culture Techniques MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Evaluation Study MeSH
- Research Support, Non-U.S. Gov't MeSH
Medicinal and aromatic plants represent an outstanding source of green active ingredients for a broad range of real-world applications. In the present study, we investigated the insecticidal potential of the essential oils obtained from three medicinal and aromatic plants of economic importance in Algeria, Artemisia campestris, Pulicaria arabica, and Saccocalyx satureioides. Gas chromatography coupled with mass spectrometry (GC-MS) was used to study the essential oil chemical compositions. The three essential oils were tested against a mosquito vectoring filariasis and arboviruses, i.e., Culex quinquefasciatus, a fly pest acting also as pathogens vector, Musca domestica, and an agricultural moth pest, i.e., Spodoptera littoralis, using WHO and topical application methods, respectively. The essential oil from A. campestris, containing β-pinene (15.2%), α-pinene (11.2%), myrcene (10.3%), germacrene D (9.0%) (Z)-β-ocimene (8.1%) and γ-curcumene (6.4%), showed remarkable toxicity against C. quinquefasciatus (LC50 of 45.8 mg L-1) and moderate effects (LD50 of 99.8 μg adult-1) against M. domestica. Those from P. arabica and S. satureioides, containing epi-α-cadinol (23.9%), δ-cadinene (21.1%), α-cadinol (19.8%) and germacrene D-4-ol (8.4%), and thymol (25.6%), α-terpineol (24.6%), borneol (17.4%) and p-cymene (11.4%), respectively, were more active on S. littoralis showing LD50 values of 68.9 and 61.2 μg larva-1, respectively. Based on our results, the essential oil from A. campestris may be further considered a candidate ingredient for developing botanical larvicides.
- MeSH
- Culex * MeSH
- Insecticides * MeSH
- Larva MeSH
- Plants, Medicinal * MeSH
- Oils, Volatile * MeSH
- Artemisia * MeSH
- Pulicaria * MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Algeria MeSH
Terpenoids, one of the major components of essential oils, are known to exert potent antifungal activity against yeast Saccharomyces cerevisiae. They have been the subject of a considerable number of investigations that uncovered extensive pharmacological properties, including antifungal and antibacterial effects. However, their mechanism of action remains elusive. In order to use terpenoids as the antimicrobial and antifungal agents in food preservation in a rational way, a good knowledge of their mode of action is required. We hypothesized that the cellular membrane is the main target site for the antifungal agents, and that structural properties of these agents are key to penetrate and act upon phospholipid bilayers. In this study, we thus aimed to study the effect of terpenoids on the cell membrane integrity, with the focus on both their structural properties, such as the presence of aromatic ring or hydroxyl group; and their hydrophobicity, as a consequence of these structural features. We first uncovered the antifungal properties of phenolic terpenoids thymol, carvacrol and eugenol, cyclic terpenes limonene, carveol, and α-pinene, in addition to the closely related compounds of different chemical structures. We then examined the cell membrane deterioration upon the addition of these reagents. Our results demonstrate that the presence of a phenolic -OH moiety is crucial, and hydrophobicity gained by the aromatic ring structure contributes to the ability of penetration and damaging yeast plasma membrane to achieve high antifungal activity.
- MeSH
- Antifungal Agents chemistry pharmacology MeSH
- Cell Membrane drug effects metabolism MeSH
- Hydrophobic and Hydrophilic Interactions MeSH
- Microbial Sensitivity Tests MeSH
- Molecular Structure MeSH
- Oils, Volatile chemistry pharmacology MeSH
- Cell Membrane Permeability drug effects MeSH
- Saccharomyces cerevisiae drug effects metabolism MeSH
- Terpenes chemistry pharmacology MeSH
- Structure-Activity Relationship MeSH
- Publication type
- Journal Article MeSH
It is generally believed that antibacterial essential oils have the potential to become one of the alternatives in preventing diarrheal diseases of monogastric animals. The disadvantage is their low efficiency per oral due to easy degradation during digestion in the stomach. This study compares the efficacy of chitosan, alginate-chitosan, guar gum-chitosan, xanthan gum-chitosan and pectin-chitosan nanocapsules to the synthesis of pH-responsive biopolymeric nanocapsule for Thymus vulgaris, Rosmarinus officinalis and Syzygium aromaticum essential oils. Using spectrophotometric approach and gas chromatography, release kinetics were determined in pH 3, 5.6 and 7.4. The growth rates of S. aureus and E. coli, as well as minimal inhibition concentration of essential oils were studied. The average encapsulation efficiency was 60%, and the loading efficiency was 70%. The size of the nanocapsules ranged from 100 nm to 500 nm. Results showed that chitosan-guar gum and chitosan-pectin nanocapsules released 30% of essential oils (EOs) at pH 3 and 80% at pH 7.4 during 3 h. Similar release kinetics were confirmed for thymol, eugenol and α-pinene. Minimal inhibition concentrations of Thymus vulgaris and Syzygium aromaticum essential oils ranged from 0.025 to 0.5%. Findings of this study suggest that the suitable pH-responsive nanocapsule for release, low toxicity and antibacterial activity is based on chitosan-guar gum structure.
- MeSH
- Anti-Bacterial Agents chemistry pharmacology MeSH
- Erythrocytes cytology drug effects MeSH
- Escherichia coli drug effects growth & development MeSH
- Hemolysis drug effects MeSH
- Hydrogen-Ion Concentration MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Nanocapsules administration & dosage chemistry MeSH
- Oils, Volatile chemistry pharmacology MeSH
- Polymers chemistry MeSH
- Staphylococcus aureus drug effects growth & development MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Personal care product consumption has increased in the last decades. A typical representative ingredient, i.e., triclosan, was identified in the scientific literature as an endocrine disruptor, and its use is restricted in several applications. Oral hygiene formulations contain various compounds, including synthetic phenol derivatives, quaternary ammonium compounds (QACs), various amides and amines, or natural essential oils containing terpenes. The aim of this paper was to explore possible endocrine-disrupting effects of these most-used compounds. For this purpose, two different assays based on recombinant yeast (BMAEREluc/ERα; BMAEREluc/AR) and human cell lines (T47D; AIZ-AR) were employed to investigate the agonistic and antagonistic properties of these compounds on human estrogen and androgen receptors. The results showed that none of the compounds were indicated as agonists of the steroid receptors. However, octenidine (OCT, QAC-like) and hexadecylpyridinium (HDP, QAC) were able to completely inhibit both androgenic (IC50 OCT = 0.84 μM; IC50 HDP = 1.66 μM) and estrogenic (IC50 OCT = 0.50 μM; IC50 HDP = 1.64 μM) signaling pathways in a dose-dependent manner. Additionally, chlorhexidine was found to inhibit the 17β-estradiol response, with a similar IC50 (2.9 μM). In contrast, the natural terpenes thymol and menthol were found to be competitive antagonists of the receptors; however, their IC50 values were higher (by orders of magnitude). We tried to estimate the risk associated with the presence of these compounds in environmental matrices by calculating hazard quotients (HQs), and the calculated HQs were found to be close to or greater than 1 only when predicted environmental concentrations were used for surface waters.
- MeSH
- Receptors, Androgen metabolism MeSH
- Anti-Bacterial Agents pharmacology therapeutic use MeSH
- Humans MeSH
- Receptors, Estrogen metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
A number of papers reporting antimicrobial properties of extracts, essential oils, resins and various classes of compounds isolated from higher plants have been published in recent years; however, a comprehensive analysis of plant-derived antimicrobial agents currently applied in practice for the improvement of human health is still lacking. This review summarizes data on clinical efficacy, antimicrobial effects and the chemistry of commercially available antibacterial and antifungal agents of plant origin currently used in the prevention and treatment of gastrointestinal, oral, respiratory, skin, and urinary infections. As a result of an analysis of the literature, more than 40 plant-derived over-the-counter pharmaceuticals, dietary supplements, cosmetics, herbal medicines, and functional foods containing complex mixtures (e.g. Glycyrrhiza glabra extract, Melaleuca alternifolia essential oil, and Pistacia lentiscus resin), pure compounds (e.g. benzoic acid, berberine, eucalyptol, salicylic acid and thymol) as well as their derivatives and complexes (e.g. bismuth subsalicylate and zinc pyrithione) have been identified. The effectiveness of many of these products is illustrated by results of clinical trials and supported by data on there in vitro antimicrobial activity. A broad spectrum of various commercial products currently available on the market and their welldocumented clinical efficacy suggests that plants are prospective sources for the identification of new types of antimicrobial agents in future. Innovative approaches and methodologies for effective proof-of-concept research and the development of new types of plant-derived products effective against recently emerging problems related to human microbial diseases (e.g. antimicrobial resistance) are also proposed in this review.
- MeSH
- Anti-Bacterial Agents chemistry pharmacology therapeutic use MeSH
- Antifungal Agents chemistry pharmacology therapeutic use MeSH
- Biological Products chemistry pharmacology therapeutic use MeSH
- Glycyrrhiza chemistry MeSH
- Humans MeSH
- Melaleuca chemistry MeSH
- Microbial Sensitivity Tests MeSH
- Molecular Structure MeSH
- Pistacia chemistry MeSH
- Plant Extracts chemistry MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
