4-Carvomenthenol ameliorates the murine combined allergic rhinitis and asthma syndrome by inhibiting IL-13 and mucus production via p38MAPK/NF-κB signaling pathway axis.

The aim of this study was to analyze the 4-carvomenthenol (carvo) oral treatment on the experimental model of the combined allergic rhinitis and asthma syndrome (CARAS). BALB/c mice were OVA-sensitized on day zero and 7th (50 µg/mL OVA in 10 mg/mL Al (OH)3) and OVA-challenged (5 mg/mL, 20 µL/animal) for three weeks. In the last week, the animals were dally challenged with aerosol of OVA and the carvo treatment (12.5, 25 or 50 mg/kg) occurred one hour before each OVA-challenge. Data were analyzed and p < 0.05 was considered significant. Carvo (12.5-50 mg/kg) decreased significantly the eosinophil migration into the nasal (NALF) and bronchoalveolar (BALF) cavities as well as on the nasal and lung tissues of sick animals. The treatment also decreased mucus production on both tissue sections stained with PAS (periodic acid-Schiff satin). In addition, the histological analyzes demonstrated that sick mice presented hyperplasia and hypertrophy of the lung smooth muscle layer followed by increasing of extracellular matrix and carvo (50 mg/kg) inhibited these asthmatic parameters. We analyzed the allergic rhinitis signals as nasal frictions and sneezing and observed that carvo decreased these two signals as well as serum OVA-specific IgE titer, type 2 cytokine synthesis, mainly IL-13, with increasing of IL-10 production. Decreasing of IL-13 production corroborated with decreasing of mucus production and these effects were dependent on p38MAPK/NF-κB(p65) signaling pathway inhibition. Therefore, these data demonstrated that a monoterpene of essential oils presents anti-allergic property on an experimental model of CARAS suggesting a new drug prototype to treat this allergic syndrome.

Reconsidering Hydrosols as Main Products of Aromatic Plants Manufactory: The Lavandin (Lavandula intermedia) Case Study in Tuscany.

: The present work evaluates for the first time two Lavandin (Lavandula × intermedia Emeric ex Loisel.) aromatic waters obtained from different plant organs, the flowers and the stems. Both extracts were analysed by GC-MS, which indicates semi-quantitative differences between the major metabolites including linalool, 1,8-cineole, camphor, linalyl acetate and 4-terpineol. 1H-NMR and LC-MS investigation confirmed the presence of these compounds. Moreover, behavioural tests with the food insect pest Tribolium confusum (Coleoptera Tenebrionidae) showed a good repellency for both hydrosols extracts with RD50 values of 3.6 and 3.3 µL cm-2 for the flowers and stems, respectively; at the higher concentrations, however, the hydrosol extract from the flowers is expected to be more effective than the one from the stems. The effect of the flowers and stems aromatic water of Lavandin on seed germination of Raphanus sativus was also evaluated. Results showed that seed germination was completely inhibited by flowers hydrolate, having a possible application as natural herbicide. The overall experience with these Lavandin extracts indicates the potential of improved hydrolates to become the main distillation products, rather than by-products, of the aromatic plants manufacturing; this stimulates further discussions about the potential positive impacts that such a shift could have in the context of ecopharmacognosy.

A Milestone In Botanical Mosquito Repellents: Novel PMD-Based Formulation Protects More Than Twice As Long As High-Concentration Deet and Other Leading Products.

The use of skin-applied repellents is the primary method recommended by the Centers for Disease Control and Prevention for personal protection against biting mosquitoes. Historically, the majority of long-efficacy mosquito repellents have been N,N diethyl-3-methylbenzamide (deet)-based. Recently, a variety of new botanical formulations have been marketed, but their protection times generally continue to fall well short of high-concentration deet products. We present a laboratory arm-in-cage study of a Neo-Innova® repellent that has a prolonged action "NEO-PART®" (Prolonged Action Release Technology) formulation with 40% Citriodiol®. This formulation provides the botanical molecule para-menthane 3,8-diol (PMD) at 25% w/v of the total formulation. Against Aedes aegypti, Neo-Innova's mean complete protection time (CPT; 14.2 h) was approximately 2 to 3 times longer than that of 5 leading high-performance repellents marketed in the USA, including 25% deet and a 20% PMD ethanolic formulation. When testing Neo-Innova, 5 of the 6 subjects had no landings after 15 h. The 6th had single landings at 10 and 11 h (individual CPT of 10 h), but received no additional landings in further exposures made at 13 and 15 h. Neo-Innova repellency against Culex quinquefasciatus was similarly prolonged. The tremendous increment in repellency duration observed for the Neo-Innova product, when compared with both current standard and botanical repellent options, represents a milestone in repellent development and supports "once-a-day" applications as a practical strategy for personal protection against mosquitoes.

A Novel Ileocolonic Release Peppermint Oil Capsule for Treatment of Irritable Bowel Syndrome: A Phase I Study in Healthy Volunteers.

INTRODUCTION: Peppermint oil (PO) has been shown to reduce abdominal pain in patients with irritable bowel syndrome (IBS). PO is assumed to induce intestinal smooth muscle relaxation and desensitization of nociceptive nerve afferents. To increase colonic PO concentration, an ileocolonic release peppermint oil (IC-PO) capsule has been developed. The aim of this study was to compare pharmacokinetic parameters of the currently available small intestinal release PO (SI-PO) and the novel IC-PO. METHODS: In this randomized, double-blind, crossover study, subjects received 182 mg of either SI-PO or IC-PO in a crossover design with a washout period of more than 14 days. Blood samples were collected to determine menthol glucuronide concentrations. RESULTS: Eight healthy volunteers (50% female, median age 22) were included. The time to reach the maximum concentration (Tmax) of IC-PO was significantly longer compared to SI-PO with a median (IQR) of 360 (360-405) versus 180 (120-180) min. The lag time (Tlag) was significantly longer with a median (IQR) of 225 (204-284) for IC-PO compared to 37 (6-65) min for SI-PO. The areas under the menthol glucuronide plasma concentration-time curves were significantly smaller with a median (IQR) of 2331 µg h/L (2006-2510) for IC-PO compared to 2623 µg h/L (2471-2920) for SI-PO. No significant differences were found in peak concentrations and elimination half-lives. CONCLUSION: IC-PO has a significantly delayed peak menthol glucuronide concentration and Tlag, both pointing to the release of PO in the more distal part of the intestine. This may enhance therapeutic efficacy as it results in increased exposure of colonic mucosal afferents to the PO. A randomized controlled trial investigating the efficacy of SI and IC-PO in IBS is currently ongoing. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02291445, EudraCT database 2014-004195-32.

Tea tree oil: contact allergy and chemical composition.

In this article, contact allergy to, and the chemical composition of, tea tree oil (TTO) are reviewed. This essential oil is a popular remedy for many skin diseases, and may be used as neat oil or be present in cosmetics, topical pharmaceuticals and household products. Of all essential oils, TTO has caused most (published) allergic reactions since the first cases were reported in 1991. In routine testing, prevalences of positive patch test reactions have ranged from 0.1% to 3.5%. Nearly 100 allergic patients have been described in case reports and case series. The major constituents of commercial TTO are terpinen-4-ol, γ-terpinene, 1,8-cineole, α-terpinene, α-terpineol, p-cymene, and α-pinene. Fresh TTO is a weak to moderate sensitizer, but oxidation increases its allergenic potency. The major sensitizers appear to be ascaridole, terpinolene, α-terpinene, 1,2,4-trihydroxymenthane, α-phellandrene, and limonene. The clinical picture of allergic contact dermatitis caused by TTO depends on the products used. Most reactions are caused by the application of pure oil; cosmetics are the culprits in a minority of cases. Patch testing may be performed with 5% oxidized TTO. Co-reactivity to turpentine oil is frequent, and there is an overrepresentation of reactions to fragrance mix I, Myroxylon pereirae, colophonium, and other essential oils.

DEET (N,N-diethyl-meta-toluamide)/PMD (para-menthane-3,8-diol) repellent-treated mesh increases Culicoides catches in light traps.

Biting midges (Culicoides spp.) are vectors of bluetongue and Schmallenberg viruses. Treatment of mesh barriers is a common method for preventing insect-vectored diseases and has been proposed as a means of limiting Culicoides ingression into buildings or livestock transporters. Assessments using animals are costly, logistically difficult and subject to ethical approval. Therefore, initial screening of test repellents/insecticides was made by applying treatments to mesh (2 mm) cages surrounding Onderstepoort light traps. Five commercial treatments were applied to cages as per manufacturers' application rates: control (water), bendiocarb, DEET/p-menthane-3,8-diol (PMD) repellent, Flygo (a terpenoid based repellent) and lambda-cyhalothrin. The experimental design was a 5 × 5 Latin square, replicated in time and repeated twice. Incongruously, the traps surrounded by DEET/PMD repellent-treated mesh caught three to four times more Obsoletus group Culicoides (the commonest midge group) than the other treatments. A proposed hypothesis is that Obsoletus group Culicoides are showing a dose response to DEET/PMD, being attracted at low concentrations and repelled at higher concentrations but that the strong light attraction from the Onderstepoort trap was sufficient to overcome close-range repellence. This study does not imply that DEET/PMD is an ineffective repellent for Culicoides midges in the presence of an animal but rather that caution should be applied to the interpretation of light trap bioassays.

Two new menthane monoterpenes from Illicium wardii.

Two new menthane monoterpenes, wardicines A (1) and B (2), were isolated from the fruits of Illicium wardii A.C. Smith. Their structures were determined on the basis of spectroscopic data analysis. Cytotoxicities of compounds 1 and 2 against three human tumor cell lines A549, HCT-116, and CCRF-CEM were also evaluated, but no significant activities were observed for the two compounds.

Identification of insecticidal constituents of the essential oils of Dahlia pinnata Cav. against Sitophilus zeamais and Sitophilus oryzae.

The aim of this research was to determine the chemical composition of the essential oils of Dahlia pinnata, their insecticidal activity against Sitophilus zeamais and Sitophilusoryzae and to isolate insecticidal constituents. Based on bioactivity-guided fractionation, active constituents were isolated and identified as D-limonene, 4-terpineol and α-terpineol. Essential oils and active compounds tested exhibited contact toxicity, with LD50 values ranging from 132.48 to 828.79 µg/cm(2) against S. zeamais and S. oryzae. Essential oils possessed fumigant toxicity against S. zeamais and S. oryzae with LC50 from 14.10 to 73.46 mg/L. d-Limonene (LC50 = 4.55 and 7.92 mg/L) showed stronger fumigant toxicity against target insects. 4-Terpineol (88 ± 8%) and d-limonene (87 ± 5%) showed the strongest repellency against S. zeamais and S. oryzae, respectively. The results indicate that essential oils and insecticidal constituents have potential for development into natural fumigants, insecticides or repellents for control of the stored-product insect pests.

New withanolide, acyl and menthyl glucosides from fruits of Withania coagulans Dunal.

The fruits of Withania coagulans Dunal (family: Solanaceae) are sweet, sedative, emetic, alterative and diuretic; used to treat asthma, biliousness, strangury, wounds, dyspepsia, flatulent colic, liver complaints and intestinal infections. Phytochemical investigation of the fruits yielded a withanolide tetraglucoside identified as (20S, 22R)-5alpha, 20alpha-diacetoxy-6beta-hydroxy- 1-oxowitha-2,24-dienolide-6-beta-D-glucopyranosyl-(6' --> 1")-beta-D-glucopyranosyl-(6" --> 1''')-beta-D-glucopyranosyl-(6''' --> 1''''-beta-D-glucopyranoside), a capryloyl hexaglucoside formulated as n-octanoyl-beta-D-glucopyranosyl-(6a --> 1b)-beta-D-glucopyranosyl-(6b --> c)-beta-D-glucopyranosyl-(6c --> 1d)-beta-D-glucopyranosyl-(6d --> 1e)-glucopyranosyl-(6e --> 1f)-glucopyranoside and a menthyl tetraglucoside characterized as menthol-O-alpha-L-glucopyranosyl-(2a --> 1b)-O-alpha-L-glucopyranosyl-(2b --> 1c)-O-alpha-L-glucopyranosyl-(2c --> 1d)-O-alpha-L-glucopyranoside along with three fatty acid esters, n-nonacosanyl linolenate, n-octacosanyl linolenate and n-heptacosanyl linolenate. The structures of the isolated phytoconstituents have been established on the basis of spectral data analysis and chemical means.

A push-pull system to reduce house entry of malaria mosquitoes.

BACKGROUND: Mosquitoes are the dominant vectors of pathogens that cause infectious diseases such as malaria, dengue, yellow fever and filariasis. Current vector control strategies often rely on the use of pyrethroids against which mosquitoes are increasingly developing resistance. Here, a push-pull system is presented, that operates by the simultaneous use of repellent and attractive volatile odorants. METHOD/RESULTS: Experiments were carried out in a semi-field set-up: a traditional house which was constructed inside a screenhouse. The release of different repellent compounds, para-menthane-3,8-diol (PMD), catnip oil e.o. and delta-undecalactone, from the four corners of the house resulted in significant reductions of 45% to 81.5% in house entry of host-seeking malaria mosquitoes. The highest reductions in house entry (up to 95.5%), were achieved by simultaneously repelling mosquitoes from the house (push) and removing them from the experimental set-up using attractant-baited traps (pull). CONCLUSIONS: The outcome of this study suggests that a push-pull system based on attractive and repellent volatiles may successfully be employed to target mosquito vectors of human disease. Reductions in house entry of malaria vectors, of the magnitude that was achieved in these experiments, would likely affect malaria transmission. The repellents used are non-toxic and can be used safely in a human environment. Delta-undecalactone is a novel repellent that showed higher effectiveness than the established repellent PMD. These results encourage further development of the system for practical implementation in the field.

[Mucolytic therapy of sinusitis].

The authors overview the articles concerning the treatment of sinusitis with the use of mucolytic preparations published in the Russian-speaking and foreign literature during the period from 1987 to 2013. Special attention is given to GeloMyrtol and GeloMyrtol forte therapy. The analysis of the papers of interest has demonstrated that the herbal medicinal products based on standardized myrtol have a number of advantages over other preparations of the same type. It is concluded, taking into consideration the evidence-based effectiveness of GeloMyrtol and simplicity of its application, that this remedy can be prescribed to the patients suffering from sinusitis.

A multi-centre, randomised, double-blind, placebo-controlled clinical trial on the efficacy and tolerability of GeloMyrtol® forte in acute bronchitis.

UNLABELLED: GeloMyrtol® forte (Myrtol®) is a phytomedicine obtained by distillation from essential oils. The trial was conducted to confirm the efficacy of Myrtol® in the treatment of acute bronchitis. METHODS: Patients with acute bronchitis and without confounding co-morbidity or co-medication were randomly assigned to treatment with either Myrtol® 300 mg 4 times daily or matched placebo in double-blind, parallel-group fashion. Signs and symptoms were evaluated by the investigator at baseline and after 7, 10 and 14 days of treatment; intake of medication, wellbeing and symptoms were recorded daily by the patient in the patients' diaries. FINDINGS: 413 patients were enrolled and randomised (Myrtol®: 202; Placebo: 211); 398 had at least one on-treatment efficacy evaluation (Myrtol®: 196; Placebo: 202). The mean change in coughing fits from D01 (baseline) to D07-D09 (after about one week treatment) was 62.1% (95% CI: 57.6-66.6%) and 49.8% (95% CI: 44.6-55.0%) for treatment with Myrtol® and placebo, respectively (p<0.0001). With Myrtol®, the median time to 50% reduction in coughing fits was statistically significantly shorter and there were more patients without day-time coughing fits; there also were statistically significantly less day-time coughing fits, less difficulty coughing up, less sleep disturbance due to night-time coughing; with Myrtol® there was less symptomatic impairment (composite bronchitis severity score and subscores) and significant more patients had a clinically satisfying response to the investigational treatment.Both treatments were generally well tolerated. CONCLUSIONS: Myrtol® is statistically significantly superior to placebo in treating acute bronchitis.

Efficacy of DEET and non-DEET-based insect repellents against bites of Simulium damnosum vectors of onchocerciasis.

Coping strategies including smoke screens are used against nuisance bites of Simulium damnosum Theobald (Diptera:Simuliidae) in onchocerciasis endemic communities. To find more effective alternatives, the efficacy of commercially available N,N-diethyl-3-methylbenzamide (DEET) products with active concentrations of 9.5, 13, 25, 50 and 98.1-100% and 'NO MAS,' (active component: para-menthane-3,8-diol and lemon grass oil) were tested at Bui-Agblekame, Ghana. A Latin square study design was implemented using eight groups of two vector collectors each, who used repellents (treatment), mineral oil or nothing each day until the end of the study. Flies were caught and their numbers each hour recorded using the standard methods for onchocerciasis transmission studies. T-tests were used to compare the mean duration of protection and a one-way analysis of variance controlling for catchers and repellents was performed. Tukey's test was used to compare protection by repellents and mineral oil. The highest percentage protection was 80.8% by NO MAS and the least 42.5% by the 13% DEET product. The period of absolute protection was 5 h by NO MAS and 1 h by 50% DEET product. No significant increase in protection was offered beyond 25% active DEET products and no significance was observed in terms of catcher × repellent effect (F = 1.731, d.f. = 48, P = 0.209).

[GC-MS study on fingerprint of volatile oil from Kadsura heteroclita].

OBJECTIVE: To study the fingerprint of volatile oil from Kadsura heteroclita by GC-MS. METHODS: 10 batches of Kadsura heteroclita were analyzed by GC-MS. TIC profiles were evaluated by" computer aided similarity evaluation system". The characteristic peaks in chromatograms were identified. Hierarchical clustering analysis was performed by SPSS. RESULTS: 23 main peaks was established preliminarily from 10 batches. Resemblance values of 10 batches were a little low. 10 batches were divided into three main clusters based on hierarchical clustering analysis. CONCLUSION: With Good reproducibility, fingerprints established for volatile oil from Kadsura heteroclita provides an effective method for quality control.