GC-MS Analysis and Antimicrobial Activity of the Essential Oil from the Stem of the Jordanian Toothbrush Tree Salvadora persica.

Abstract

Chemical composition of the essential oil of the stem of the toothbrush tree Salvadora persica. L. grown in Jordan was determined by gas chromatography-mass spectrometry (GC-MS). The oil obtained by hydrodistillation (yield: 0.6% w/w) was determined as a mixture of monoterpene hydrocarbons (11%), oxygenated monoterpenes (54%), and sesquiterpene hydrocarbons (21%). The major components identified were 1,8-cineole (eucalyptol) (46%), α-caryophellene (13.4%), β-pinene (6.3%), and 9-epi.-(E.)-caryophellene. The antimicrobial activity of the volatile oils and aqueous and alcohol extracts of the plant has been also evaluated. Among all tested fractions, the volatile oils exhibited potent activity against both sensitive and resistant strains of Pseudomonas aeruginosa. (Schroeter and Migula) and Staphylococcos aureus. (Rosenbach). Moreover, the oil revealed significant inhibition against Candida albicans. (C. P. Robin) and Trichosporon cutaneum. (Beurm, Govgerot and Vaucher).     

Anti-inflammatory and gastroprotective potential of leaf essential oil of Cinnamomum glanduliferum in ethanol-induced rat experimental gastritis

Context: Nothing could be found in the literature concerning Cinnamomum glanduliferum (Wall) Meissn (Lauraceae) bark (CG) in Egypt.

Objective: To investigate CG volatile oil chemically and its anti-inflammatory and gastroprotective effects.

Materials and methods: Essential oils were investigated by GC-MS. Leaves oil was assessed at doses of 250, 500 and 1000?mg/kg for its anti-inflammatory effect against carrageenan-induced rat oedema model. Serum inflammation markers were measured. The gastro-protective effect of the same doses of the volatile oil was also tested in ethanol-induced non-ulcerative gastritis model in rats. Stomach oxidative stress markers were examined following 1?h after intragastric ethanol administration.

Results: Twenty-five and 20 compounds were identified from leaf and branch oils, respectively (98.85 and 99.13%). The major ones were: eucalyptol (59.44%; 55.74%), sabinene (14.99%; 7.12%), α-terpineol (6.44%; 9.81%), α-pinene (5.27%; 4.71%). Following 4?h of treatment leaves volatile oil at doses of 250, 500 and 1000?mg/kg significantly reduced paw volume to 94, 82 and 69%, respectively. The same doses significantly reduced COX-2 activity to 73.8, 50.7 and 21.4?nmol/min/mL, respectively. A significant reduction of PGE2 concentration was observed (2.95?±?0.2, 2.45?±?0.15 and 1.75?±?0.015?pg/mL). CG oil exhibited a significant modulatory effect on ethanol-induced gastritis in rats as the level of NO reduced to 32, 37 and 41?μM nitrate/g and also a significant inhibition of lipid peroxidation was observed via reduction of MDA concentration (1.15, 1.11 and 1.04?nmol/g).

Conclusion: CG volatile oil exhibited an anti-inflammatory effect and protected against ethanol-induced non-ulcerative gastritis.     

Chemical composition,antimicrobial, and cytotoxicity studies on S. erianthum and S. macranthum essential oils

Context: Solanum erianthum D. Don and Solanum macranthum Dunal (Solanaceae) are widely used in traditional medicine. The leaves act as an abortifacient and in particular to treat leucorrhoea, sores, and skin irritations.

Objective: This study was undertaken to characterize the volatile constituents of the leaf and fruit essential oils of S. erianthum and S. macranthum; their antimicrobial and in vitro cytotoxic bioassay against human breast and prostate tumor cells.

Methods: The volatile oils were obtained by hydrodistillation and analyzed for their constituents by gas chromatography-mass spectrometry (GC-MS). Minimum Inhibitory Concentrations (MIC) were determined using the microbroth dilution technique while the cytotoxic potentials were evaluated using the Cell Titre 96^(R) AQ_ueous Non-Radioactive Cell Proliferation Assay method.

Results: Solanum erianthum essential oils were characterized by the abundance of α-terpinolene (17.8%), α-phellandrene (17.5%), p-cymene (15.7%) and β-pinene (11.7%) in the leaves; α-humulene (23.1%), humulene epoxide II (20.0%), caryophyllene oxide (16.5%), methyl salicylate (11.8%) and β-caryophyllene (10.9%) in the fruits. The leaf oil of S. macranthum consisted of (E)-phytol (29.0%), pentadecanal (28.1%) and pentadecane (7.7%) while the major fruit oil constituents were α-humulene (36.5%), β-caryophyllene (17.8%), ethyl palmitate (9.4%), and methyl salicylate (8.2%). Solanum erianthum leaf volatile oil demonstrated potent inhibitory activity against Hs 578T and PC-3 human breast and prostate tumor cells respectively. In addition, the Solanum essential oils exhibited significant antimicrobial activity (19.5–625 µg/mL) on pathogens employed in the assay.

Conclusion: The Solanum essential oils possess strong antimicrobial activity in addition to the potent cytotoxic potential of S. erianthum leaf oil against Hs 578T and PC-3 cells.     

Phytochemical composition,anti-inflammatory activity and cytotoxic effects of essential oils from three Pinus spp.

Context: Inflammation and cell differentiation lead to a number of severe diseases. In the recent years, various studies focused on the anti-inflammatory and anticancer activity of essential oils (EOs) of numerous plants, including different Pinus species.

Objective: The phytochemical composition, anti-inflammatory and cytotoxic activity of EOs from needles and twigs of Pinus heldreichii Christ (Pinaceae) and P. peuce Griseb., and from needles, twigs and cones of P. mugo Turra were determined.

Materials and methods: For separation and identification of the EOs, gas chromatography/flame ion detector (GC/FID) and GC/mass spectrometry were performed. The amount of secreted IL-6 in a lipopolysaccharide (LPS)-stimulated macrophage model was quantified (concentration of oils: 0.0001–0.2%, 3?h incubation). Cytotoxicity on the cancer cell lines HeLa, CaCo-2 and MCF-7 were determined using a MTT (Thiazolyl Blue Tetrazolium Bromide) assay (concentration of oils: 0.001–0.1%, 24?h incubation).

Results: The most prominent members in the oils include: δ-3-carene, α-pinene and linalool-acetate (P. mugo); α-pinene, β-phellandrene and β-pinene (P. peuce); limonene, α-pinene and (E)-caryophyllene (P. heldreichii). EOs showed significant cytotoxic effects on cancer cell lines (IC₅₀ 0.007 to >0.1%), with a reduction in cell viability with up to 90% at a concentration of 0.1%, and anti-inflammatory activity (IC₅₀ 0.0008–0.02%) with a reduction of IL-6 secretion with up to 60% at a concentration of 0.01%.

Discussion and conclusion: The EOs of needles and twigs from P. peuce and P. heldreichii as well as of needles, twigs and cones of P. mugo can be considered as promising agents for anticancer and anti-inflammatory drugs.     

Development of essential oils as skin permeation enhancers: penetration enhancement effect and mechanism of action

Context: Essential oils (EOs) have shown the potential to reversibly overcome the stratum corneum (SC) barrier to enhance the skin permeation of drugs.

Objective: The effectiveness of turpentine, Angelica, chuanxiong, Cyperus, cinnamon, and clove oils were investigated for the capacity and mechanism to promote skin penetration of ibuprofen.

Materials and methods: Skin permeation studies of ibuprofen across rat abdominal skin with the presence of 3% w/v EOs were carried out; samples were withdrawn from the receptor compartment at 8, 10, 22, 24, 26, 28, 32, 36, and 48?h and analyzed for ibuprofen content by the HPLC method. The mechanisms of penetration enhancement of EOs were further evaluated by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) analysis and determination of the properties of EOs. Moreover, the toxicities of EOs on skin cells were also measured.

Results: The enhancement ratio (ER) values of turpentine, Angelica, chuanxiong, Cyperus, cinnamon, clove oils and azone were determined to be 2.23, 1.83, 2.60, 2.49, 2.63 and 1.97, respectively. Revealed by ATR-FTIR analysis, a linear relationship (r?=?0.9045) was found between the ER values and the total of the shift of peak position of SC lipids. Furthermore, the results of HaCaT skin cell toxicity evaluation revealed that the natural EOs possessed relatively lower skin irritation potential.

Conclusion: Compared with azone, the investigated EOs possess significantly higher penetration enhancement effect and lower skin toxicity. EOs can promote the skin permeation of ibuprofen mainly by disturbing rather than extracting the SC lipids.     

The association between blood eosinophil count and benralizumab efficacy for patients with severe,uncontrolled asthma: subanalyses of the Phase III SIROCCO and CALIMA studies

Objective: Benralizumab, an anti-eosinophilic monoclonal antibody, in combination with high-dosage inhaled corticosteroids and long-acting β₂-agonists (ICS/LABA), significantly reduced asthma exacerbations, improved lung function, and reduced symptoms for patients with severe, uncontrolled asthma with blood eosinophil counts ≥300 cells/μL in the Phase III SIROCCO and CALIMA studies. To understand the efficacy and safety of benralizumab for patients with eosinophil-driven disease with blood eosinophil counts lower than 300 cells/μL, we evaluated the effect of applying an eosinophil cutoff of ≥150 cells/μL.

Methods: Adult patients with uncontrolled asthma despite high-dosage ICS/LABA?±?additional asthma controller(s) received subcutaneous benralizumab 30?mg every 8 weeks (Q8W; first three doses every 4 weeks) or placebo for 48 (SIROCCO) or 56 (CALIMA) weeks. Efficacy measures including annual exacerbation rate, prebronchodilator FEV₁, and total asthma symptom score were analyzed by baseline blood eosinophil counts ≥150 vs. <150 cells/μL.

Results: Benralizumab reduced asthma exacerbation rates by 42% in SIROCCO (rate ratio?=?0.58; 95% CI?=?0.46–0.74; p?n?=?325) and 36% in CALIMA (rate ratio?=?0.64; 95% CI?=?0.50–0.81; p?n?=?300) vs. placebo (n?=?306 for SIROCCO, n?=?315 for CALIMA) for patients with blood eosinophil counts ≥150 cells/μL. Benralizumab increased prebronchodilator FEV₁ (both studies, p?≤?0.002) and improved total asthma symptom score in SIROCCO (p?=?0.009) at end of treatment vs. placebo for patients with blood eosinophil counts ≥150 cells/μL. The overall adverse events frequency was similar between treatment groups and eosinophil count cohorts.

Conclusion: These results support the efficacy and safety of benralizumab for patients with severe asthma and blood eosinophil counts ≥150 cells/μL.     

Chemical composition,antioxidant and antibacterial activities of essential oils from Ferulago angulata

Context: Ferulago angulata Boiss. (Apiaceae), a perennial aromatic herb, grows wild in Iran. The aerial parts of F. angulata are used as a flavouring in foods, especially dairy foods by indigenous people in western and southwestern Iran.

Objective: This study investigates variation in chemical compositions, antioxidant and antibacterial activities of the essential oils from F. angulata collected from natural habitats in the alpine regions of southwestern Iran.

Materials and Methods: The antimicrobial activity, minimum inhibitory concentration (MIC) and minimum bactericidal (MBC) of the essential oils were evaluated against four bacteria (Bacillus cereus, Listeria monocytogenes, Staphylococcus aureus and Salmonella typhimurium). Antioxidant activity of the oils was determined by DPPH assay.

Results: The essential oils were analyzed by GC-FID and GC/MS, which 49 volatile components were identified. There were significant differences between the various populations for oil yield and some main compounds. The major constituents of the essential oils from F. angulata were α-pinene, and cis-β-ocimene. The MICs of the essential oils were within concentration ranges from 62 to 250?μg/mL and the respective MBCs were 125 to?>?500?μg/mL. Generally, the oils from F. angulata indicated weak to moderate inhibitory activities against bacteria, especially against Listeria monocytogenes. The highest antioxidant activity was obtained from the oil of the Kallar population (IC₅₀ value_?=_?488?μg/mL) and BHT as positive control (IC_50? value =_?321?μg/mL).

Discussion and conclusion: The essential oil of F. angulata could be serving as a potential source of α-pinene and cis-β-ocimene for use in the food, cosmetic and pharmaceutical industries.     

Chemical composition and bioactivity of essential oils of Hypericum helianthemoides. Hypericum perforatum and Hypericum scabrum

Context: A number Hypericum species are well known for their therapeutic efficacy and use in traditional medicine. The various species of Hypericum have been traditionally used for the treatment of wounds, eczema, burns, trauma, rheumatism, neuralgia, gastroenteritis, ulcers, hysteria, bedwetting and depression.

Objective: This study evaluated the in vitro antioxidant, antibacterial and phytochemical properties of essential oils of Hypericum helianthemoides (Spach) Boiss., Hypericum perforatum L. and Hypericum scabrum L. (Hypericaceae) collected from alpine region of Southwest Iran.

Materials and methods: The essential oils obtained from dried flowering aerial parts of three Hypericum species were analyzed by gas chromatography and gas chromatography/mass spectrometry to determine chemical compositions. The antibacterial activity of essential oils within concentration ranges from 16 to 500?µg/mL was individually evaluated against Bacillus cereus, Listeria monocytogenes. Proteus vulgaris and Salmonella typhimurium. The 1,1-diphenyl-2-picrilhydrazyl (DPPH) radical scavenging activity of essential oils was determined using DPPH assay.

Results: Essential oil yield of H. helianthemoides. H. scabrum and H. perforatum were 0.12, 0.20 and 0.21?mL/100?g dried material, respectively. The major constituents of the essential oils were α-pinene (12.52–49.96%), β-pinene (6.34–9.70%), (E)-β-ocimene (4.44–12.54%), β-caryophyllene (1.19–5.67%), and germacrene-D (2.34–6.92%). The essential oils of three Hypericum species indicated moderate-to-good inhibitory activities against four bacteria, especially against L. monocytogenes.

Discussion and conclusion: The essential oils of the three studied Hypericum species sourced in alpine region of West Iran were rich in monoterpene and sesquiterpenes hydrocarbons. Among the three tested species, the essential oil of H. scabrum showed the highest antibacterial and antioxidant activities.     

武当玉兰花蕾及其枝条挥发油的化学成分分析和比较

用高效毛细管气相色谱法和气相色谱—质谱考察了武当玉兰花蕾及其枝条挥发油的化学成分,共检出40个组分,鉴定了其中的32个成分,并用峰面积归一法作了测定,其中含量在5%以上的有β-蒎烯、香桧烯、对-缴花烃、乙酸龙脑脂、反-丁香烯、丁香烯氧化物和β-桉油醇。比较结果表明,两者的化学成分有着明显的差别,花蕾挥发油所含倍半萜醇和倍半萜烃较枝条挥发油为多,而含单萜烃则较少。     

Chemical composition and pharmacological properties of the essential oils obtained seasonally from Lippia thymoides

Context: Lippia thymoides Mart. & Schauer (Verbenaceae) is used in folk medicine to treat wounds, fever, bronchitis, rheumatism, headaches, and weakness.

Objective: This study determinates the chemical composition of essential oils from L. thymoides, obtained at during each of the four seasons and correlates with pharmacological properties.

Materials and methods: Essential oils were obtained by hydrodistillation and analyzed by gas chromatography coupled to mass spectroscopy (GC-MS). Antioxidant activity was determined by DPPH free radical scavenging and β-carotene bleaching methods. The antimicrobial assays were performed by minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) methods. Isolated rat aorta and uterus, and guinea-pig trachea were utilized to evaluate relaxant potential in pre-contracted smooth muscle.

Results and discussion: Essential oils from leaves of L. thymoides had the sesquiterpene β-caryophyllene (17.22–26.27%) as the major constituent followed by borneol (4.45–7.36%), camphor (3.22–8.61%), camphene (2.64–5.66%), and germacrene D (4.72–6.18%). In vitro assays showed that these essential oils do not have antioxidant activity, have antimicrobial selectivity to Gram-positive bacteria Staphylococcus aureus (MIC?=?0.004?mg/mL and MMC?=?0.26–10.19?mg/mL) and Micrococcus luteus (MIC?=?0.03?mg/mL and MMC?=?8.43?mg/mL), relax isolated rat aorta (EC₅₀?=?305–544?μg/mL, with endothelium; and EC₅₀?=?150–283?μg/mL, without endothelium), and uterus (EC₅₀?=?74–257?μg/mL), and minor potency, isolated guinea-pig trachea.

Conclusions: Lippia thymoides is a source of natural products of pharmaceutical interest, being necessary additional studies to determine the substances involved in the biological activities.     

Chemical composition and acetylcholinesterase inhibitory activity of Artemisia maderaspatana essential oil

Abstract

Context: To date, there are no reports to validate the Indian traditional and folklore claims of Artemisia maderaspatana L. (syn. Grangea maderaspatana L.) (Asteraceae) for the treatment of Alzheimer’s disease.

Objective: The present study characterizes the volatile components (non-polar compounds) of A. maderaspatana and evaluates its acetylcholinesterase inhibition potential.

Materials and methods: The essential oils (yield 0.06% v/w) were obtained from fresh aerial part of A. maderaspatana. The characterization of volatile components (non-polar compounds) was performed by GC–MS data and with those of reference compounds compiled in the spectral library of in-house database. The in vitro acetylcholinesterase (AChE) inhibition of the volatile organic constituents (VOC’s) of A. maderaspatana aerial part was evaluated in varying concentration ranges (0.70–44.75?µg/mL) with Ellman’s method.

Results: The major components were α-humulene (46.3%), β-caryophyllene (9.3%), α-copaene (8.2%), β-myrcene (4.3%), Z(E)-α-farnesene (3.7%), and calarene (3.5%). Chemical variability among other Artemisia spp. from different climatic regions of India and countries namely Iran and France was observed. The experimental results showed that diverse volatile organic constituents of A. maderaspatana have significant acetylcholinesterase inhibitory activity (an IC₅₀ value of 31.33?±?1.03?µg/mL). This is the first report on the inhibition of acetylcholinesterase properties of essential oil of A. maderaspatana obtained from fresh aerial part.

Conclusions: The present results indicate that essential oil of A. maderaspatana isolated from the northern region of India could inhibit AChE moderately. Therefore, the possibility of novel AChE inhibitors might exist in VOCs of this plant.     

Biological activity of terpene compounds produced by biotechnological methods

Context Biotransformation systems are profitable tools for structural modification of bioactive natural compounds into valuable biologically active terpenoids.

Objective This study determines the biological effect of (R)-(+)-limonene and (?)-α-pinene, and their oxygenated derivatives, (a) perillyl alcohol and (S)-(+)- and (R)-(?)-carvone enantiomers and (b) linalool, trans-verbenol and verbenone, respectively, on human colon tumour cells and normal colonic epithelium.

Materials and methods Biotransformation procedures and in vitro cell culture tests were used in this work. Cells were incubated for 24?h with terpenes at concentrations of 5–500?μg/mL for NR, MTT, DPPH, and NO assays. IL-6 was determined by ELISA with/without 2?h pre-activation with 10?μg/mL LPS.

Results trans-Verbenol and perillyl alcohol, obtained via biotransformation, produced in vitro effect against tumour cells at lower concentrations (IC₅₀ value?=?77.8 and 98.8?μg/mL, respectively) than their monoterpene precursors, (R)-(+)-limonene (IC₅₀ value?=?171.4?μg/mL) and (?)-α-pinene (IC₅₀ value?=?206.3?μg/mL). They also showed lower cytotoxicity against normal cells (IC₅₀?>?500 and?>?200?μg/mL, respectively). (S)-(+)-Carvone was 59.4% and 27.1% more toxic to tumour and normal cells, respectively, than the (R)-(?)-enantiomer. (R)-(+)-limonene derivatives decreased IL-6 production from normal cells in media with or without LPS (30.2% and 13.9%, respectively), while (?)-α-pinene derivatives induced IL-6 (verbenone had the strongest effect, 60.2% and 29.1% above control, respectively). None of the terpenes had antioxidative activity below 500?μg/mL.

Discussion and conclusions Bioactivity against tumour cells decreased in the following order: alcohols?>?ketones?>?hydrocarbons. (R)-(+)-limonene, (?)-α-pinene, and their derivatives expressed diverse activity towards normal and tumour cells with noticeable enantiomeric differences.     

In vitro photo-induced cytotoxic activity of Citrus bergamia and C. medica L. cv. Diamante peel essential oils and identified active coumarins

Context: The search for innovative therapeutic approaches is gaining more interest in clinical oncology.

Objective: In the present investigation we reported the chemical profile and the photo-induced cytotoxic activity of two endemic Calabrian Citrus species (Rutaceae): Citrus bergamia Risso & Poit. and Citrus medica L. cv. Diamante.

Materials and methods: Essential oils were obtained by hydrodistillation and analyzed by GC and GC/MS. In order to evaluate the cytotoxic activity two melanoma models, such as amelanotic melanoma C32 and malignant melanoma A375, were used.

Results: The essential oil of C. bergamia was characterized by limonene, linalyl acetate, γ-terpinene, linalool and β-pinene as major components. The most abundant compounds of C. medica cv. Diamante oil were limonene, γ-terpinene, citral, geranial, β-pinene and α-pinene. Two coumarins, bergapten and citropten, were also identified in C. bergamia and C. medica cv. Diamante, respectively and tested for biological activity. Both C. bergamia and C. medica cv. Diamante oils exhibited a selective interesting activity against the A375 cell line with IC₅₀ values of 79.3 and 89.1?µg/mL, respectively, after 100?min exposure to UV irradiation. The strong antiproliferative activity demonstrated with bergapten (IC₅₀ value of 71.3?µg/mL after 20?min of irradiation) was not found with citropten.

Discussion and conclusion: Our study suggested that UV irradiation is effective in activating essential oils and in particular bergapten. This phototoxicity may be considered as a treatment option in some cases of lentigo maligna or lentigo maligna melanoma.     

Variability,toxicity, and antioxidant activity of Eupatorium cannabinum (hemp agrimony) essential oils

Content: Eupatorium cannabinum L. (Asteraceae) is as a potential source of biologically active compounds. The plant is used in traditional medicine for the treatment of diarrhea and livers diseases.

Objective: The present study provides investigation on pharmacological properties (antioxidant and toxic activities) of essential oils of E. cannabinum, collected from 11 wild populations in Lithuania.

Materials and methods: Twenty-two hemp agrimony essential oil samples were prepared by hydrodistillation according to the European Pharmacopoeia, and their chemical composition was determined by GC–FID and GC–MS. Compositional data were subjected to principal components analysis (PCA). Instead of conventional spectrophotometric methods, cyclic voltammetry (CV) and square wave voltammetry (SWV) techniques were applied to determine antioxidant activity of hemp agrimony essential oils. Meanwhile, toxicity of the oils was determined using brine shrimp (Artemia sp.) assay.

Results: Chemical profiles of E. cannabinum oils were described according to the first predominant components: germacrene D (≤22.0%), neryl acetate (≤20.0%), spathulenol (≤27.2%), and α-terpinene (11.5%). For the first time, α-zingiberene (≤7.8%) was found to be among three major constituents (as the second one) for hemp agrimony oils. SWV measurements revealed that oxidation potentials of compounds present in the oils are lower (below 0.1 V) compared with that of well-known antioxidant quercetin (0.15 V). Toxicity tests evaluated that hemp agrimony oils containing predominant amounts of germacrene D and neryl acetate were notably toxic (LC₅₀ value 16.3–22.0 μg/mL).

Conclusion: The study provided some new data concerning chemical composition and pharmaceutical properties of E. cannabinum essential oils.     

A Polydrug and Psychosocial Profile of Synthetic Cannabinoid Use in a New York City Community Sample, 2016–2017

Background: Epidemiologic reports available on synthetic cannabinoids (SCs) have focused on sociodemographics, indicating high prevalence of SC use predominantly among white, relatively affluent, males. However, there is emerging evidence suggesting high SC prevalence among socioeconomically disadvantaged, racial/ethnic minority males. Objectives: The purpose of this study is to investigate the risk correlates of SC use among psychosocial vulnerable communities. Method: The sample of 100 participants was recruited from two harm reduction-focused, community-based organizations in the South Bronx and East Harlem neighborhoods in New York City. Consented individuals 18 years and older underwent a 30- minute survey ascertaining sociodemographics, psychosocial characteristics, SC and polydrug use characteristics, and mental health history. Results: The study population was majority male (61%), Latino (56%), commonly diagnosed with psychiatric illness (67%), and with a mean age of 45.4. Those reporting SC use (74%) were more likely to be male, homeless, and report polydrug use. After adjustment, being male (AOR?=?5.64), homelessness (AOR?=?4.88) along with cocaine (AOR?=?5.63) and opiate use (AOR?=?31.1) were independently associated with SC use. The most common reasons for using SC were affordability, inability to detect SC in drug tests, and perceived physical and emotional benefits. Conclusion/importance: This work is significant in expanding the populations thought to be impacted by and understanding social disparities related to SC use. Further investigation is needed to assess the relationship between concomitant use of SC and other drug, particularly opiates. This may suggest that the sequelae of one drug may enhance or alleviate the effects of the other.     

Sulphur-containing compounds in the essential oil of Ferula alliacea roots and their mass spectral fragmentation patterns

Context GC-MS analysis is the best way to characterize volatile sulphur-containing compounds. Ferula (Apiaceae) is a genus of perennial herbs. Due to the occurrence of essential oils or oleoresins in the Ferula species, these plants usually possess strong aromatic scent. Terpenoid compounds were the most abundant constituents of Ferula oils, however, in some of Ferula species, the essential oils were dominated by volatile sulphur-containing compounds.

Objectives Ferula alliacea Boiss. is considered one of the sources of the oleo-gum-resin asafoetida. In this study, we analyzed the hydrodistilled essential oil from its dried roots and provide new data about retention indices and mass fragmentation patterns of some volatile sulphur-containing compounds that are useful for future studies on this class of compounds.

Materials and methods The roots of F. alliacea were collected during the flowering stage of plant, from Bezgh, Kashmar to Neishabour road, Khorasan-Razavi province, Iran, in June 2012. The oil was obtained by hydrodistillation using a Clevenger apparatus and analyzed by GC-MS.

Results This is the first report on phytochemical analysis of F. alliacea roots. Seventy-six components, representing 99.5% of the oil, were characterized. The major components were 10-epi-γ-eudesmol (22.3%), valerianol (12.5%), hinesol (8.3%), guaiol (7.3%) and Z-propenyl-sec-butyl trisulphide (6.5%). Predominant mass fragment ions of the identified sulphur-containing compounds are explained in this paper.

Conclusion The volatile oil of F. alliacea mostly contains oxygenated sesquiterpenes, however, its odour was dominated by sulphur-containing compounds. The most abundant sulphur-containing compound includes Z-propenyl-sec-butyl trisulphide (6.5%).     

Topical anti-inflammatory phytomedicine based on Sphagneticola trilobata dried extracts

Context: The aerial parts of Sphagneticola trilobata (L.) Pruski (Asteraceae) are popularly used to treat topical inflammation, but have not been fully investigated.

Objective: To identify polar compounds in S. trilobata extracts and develop a new topical phytomedicine based on the kaurenoic acid (KA) content while monitoring and demonstrating its topical anti-inflammatory activity.

Materials and methods: Ethanol spray-dried extract of S. trilobata was analysed by LC-MS while the KA content from semisolid was analysed by LC-UV. The extent of ear edema induced by applying 20?μL of croton oil (2.5%), arachidonic acid (AA; 2?mg/ear) and decanoylphorbol-13-acetate (TPA; 2.5?mg/ear) in mice was used to evaluate the biological activity of the semisolids, which were applied 30?min before the phlogistic agents.

Results: Eight phenylpropanoids and four oleanane-type triterpenoid saponins were identified, majority of them reported for the first time in this species, in addition to KA. The semisolid containing 1.0% of dried extract reduced the ear edema induced by croton oil [77.2?±?4.5%; ID50?=?0.49 (0.28–0.87%)], TPA (81.5?±?2.4%) and AA (39.1?±?6.9%), with decreasing effect at higher KA concentrations. This was accompanied by neutrophil migration inhibition as investigated by biochemical and histological assays.

Discussion and conclusion: The anti-inflammatory effects were (at least in part) due to the interference in protein kinase C (PKC) activation, AA-cascade products and neutrophil migration inhibition, demonstrating the efficacy of the folk topical usage of this plant. The results support the development of a novel topical anti-inflammatory phytomedicine properly standardized to treat inflammatory dermatological diseases.     

Comparative effectiveness of interferons in relapsing–remitting multiple sclerosis: a meta-analysis of real-world studies

Background: Differences between interferons have been evaluated for over 20 years. While randomized controlled trial (RCT) data is mainly used for assessments and strong data for causal inferences, it does not necessarily reflect everyday practice. Real-world data may provide additional information.

Purpose: To assess the results, quality, and representativeness of observational studies directly comparing interferons (IFNs) in RRMS.

Methods: Medline and Embase were searched for observational studies comparing IFN-beta-1a 30?mcg IM (Avonex¹), IFN-beta-1a 44?mcg SC (Rebif²) and/or IFN-beta-1b 250?mcg SC (Betaseron³). Outcomes included annualized relapse rate (ARR), proportions relapse free, confirmed progression free, treatment persistence, and neutralizing antibodies rates (NABs) measured up to 5 years of treatment. Data was combined using random effects meta-analyses. Categorical values were analyzed using chi-squared and Mann–Whitney tests.

Results: Thirty-six studies examining 32,026 patients (72.5% females, age?=?39.2?±?3.7 years, disease duration?=?5.6?±?2.0 years) were identified. Thirty-three studies investigated IFN-beta-1a IM (N?=?11,925), 30 IFN-beta-1a SC (N?=?10,684) and 34 IFN-beta-1b SC (N?=?9417). Baseline ARRs were similar (1.37?±?0.35, 1.51?±?0.27 and 1.55?±?0.23, respectively; P?=?.101) as were EDSS scores (2.24?±?0.39, 2.33?±?0.30, 2.55?±?0.38; P?=?.070) and >75% were naïve to IFNs. On treatment, ARRs were comparable (IFN-beta-1a IM 0.52?±?0.27, IFN-beta-1a SC 0.51?±?0.24, IFN-beta-1b SC 0.55?±?0.23; P?=?.595). Proportions of relapse-free patients were similar between drugs (P?>?.05 for all data points), except that IFN-beta-1a SC was superior to IFN-beta-1b SC in years 3–5 (all P?≤?.001). After 1 year, EDSS scores were comparable; after 2 years, IFN-beta-1a IM and IFN-beta-1a SC incurred less disease progression than IFN-beta-1b SC (P?P?P?Conclusions: In this comprehensive meta-analysis of real-world studies in RRMS, IFN-beta-1a IM, IFN-beta-1a SC and IFN-beta-1b SC had similar clinical profiles. When selecting an IFN, practitioners should consider observational data in their decision making process.     

Comparative effects of biological therapies on the severity of skin symptoms and health-related quality of life in patients with plaque-type psoriasis: a meta-analysis

ABSTRACT

Background: The comparative effects of biological response modifiers (BRMs) on the severity of psoriasis and its effects on health-related quality of life (HRQoL) have not been evaluated.

Objective: To conduct a meta-analysis to assess the effects of available biological agents on the severity of psoriasis, as well as to provide data on the effects of these agents on HRQoL.

Methods: Medline and other databases were searched for randomized controlled trials (≥?10 weeks’ duration in adults) comparing biological therapies for moderate-to-severe psoriasis with placebo. A Mantel–Haenszel fixed-effects model was employed to estimate the pooled relative risks (RR) of patients achieving?≥?75% reduction of baseline Psoriasis Area and Severity Index (PASI 75) after?≥?10 weeks of treatment. Similar analyses were also conducted on PASI 50 and PASI 90. Using a random-effects model, we estimated the likelihood of achieving PASI 50, PASI 75, and PASI 90 at 10–12 weeks and 24 weeks. Data on the effects of different BRMs (vs. placebo) on HRQoL were also presented. Numbers (%) of patients discontinuing treatment were presented as a general index of drug tolerability.

Results: Patients receiving infliximab 5?mg/kg intra­venously at weeks 0, 2, and 6, then every 8 weeks, had the highest RR of achieving PASI 75, with a pooled RR value of 25.48 (95% confidence interval [CI], 14.04–46.23); followed by etanercept 50?mg administered sub­cutaneously (SC) twice weekly with RR?=?11.92 (95% CI, 8.17–17.39); etanercept 25?mg SC twice weekly with RR?=?10.68 (95% CI, 6.15–18.57); efalizumab 1–2?mg/kg SC per week with RR?=?7.47 (95% CI, 5.20–10.73); and alefacept administered weekly (various doses) with RR?=?3.37 (95% CI, 2.18–5.23). (All RR values were estimated vs. placebo.) Similar findings were observed with regard to proportions of patients achieving PASI 50 and PASI 90. The random-effects analysis suggested that infliximab significantly increased the likelihood of achieving PASI 50, PASI 75, and PASI 90 compared with placebo at 10–12 weeks; however, there were no signif­icant differences between biological treatments at 24 weeks. Each BRM improved HRQoL compared with placebo according to findings from the Dermatology Life Quality Index. Proportions of patients discontinuing treatment were similar in active-treatment and placebo groups.

Conclusions: Infliximab significantly reduced disease severity by both fixed- and random-effects models. All biological therapies improved HRQoL compared with placebo, and proportions of patients discontinuing treat­ment were similar in active-treatment and placebo groups. The analysis is potentially limited by statistical factors and did not systematically account for different toxicity profiles, but the findings establish a foundation for head-to-head comparative trials.     

Clinical response to golimumab in rheumatoid arthritis patients who were receiving etanercept or adalimumab: results of a multicenter active treatment study

Objective: Evaluate the efficacy and safety of subcutaneous (SC) golimumab?+?methotrexate (MTX) in patients with active rheumatoid arthritis (RA) despite etanercept?+?MTX or adalimumab?+?MTX therapy and evaluate whether intravenous (IV) golimumab could rescue patients who were nonresponders to SC golimumab.

Methods: In this multicenter, assessor-blinded, active-switch study of patients with RA (n?=?433) with inadequate response to etanercept or adalimumab?+?MTX, patients continued MTX and received open-label SC golimumab 50?mg every 4 weeks through week 12. DAS28-ESR good responders at week 16 continued open-label SC golimumab through week 52 (Group 1); nonresponders were randomized to double-blind golimumab SC 50?mg (Group 2-SC) or IV 2?mg/kg (Group 2-IV). Week 14 ACR20 was the primary endpoint; assessments continued through week 52 and for patients in the voluntary long-term extension through week 76. A major secondary endpoint was the proportions of patients with ACR20 response at week 52 relative to week 16 in Group 2-SC and Group 2-IV.

Results: At week 14, 34.9% (p?n?=?75) achieved an ACR20 (62.7%). In Groups 2-SC (n?=?91) and 2-IV (n?=?184), 13.2% and 9.2% had an ACR20 at week 52 relative to week 16, with no significant difference between the randomized groups; 42.9% and 47.8% achieved DAS28-ESR response relative to week 0. Through week 16, 4.6% of patients had a serious adverse event. No differences in the rates or types of adverse events were observed between SC and IV golimumab from weeks 16 to 52. The trial limitations included a higher than expected discontinuation rate as a result of a programming error.

Conclusion: SC golimumab?+?MTX significantly suppressed disease activity in RA patients with inadequate response to etanercept and/or adalimumab + MTX. Patients randomized to Groups 2-SC and 2-IV had lower response rates than Group 1, with no difference between SC or IV mode of administration. The safety profile with IV golimumab was comparable to that established with SC golimumab.

Trial registration: NCT01004432, EudraCT 2009-010582-23.