Biosynthesis of dillapiole/apiole in dill (Anethum graveolens): characterization of regioselective phenylpropene O-methyltransferase.

The phenylpropene volatiles dillapiole and apiole impart one of the characteristic aromas of dill (Anethum graveolens) weeds. However, very few studies have been conducted to investigate the chemical composition of volatile compounds from different developmental stages and plant parts of A. graveolens. In this study, we examined the distribution of volatile phenylpropenes, including dillapiole, in dill plants at various developmental stages. We observed that young dill seedlings accumulate high levels of dillapiole and apiole, whereas a negligible proportion was found in the flowering plants and dry seeds. Based on transcriptomics and co-expression approaches with phenylpropene biosynthesis genes, we identified dill cDNA encoding S-adenosyl-L-methionine-dependent O-methyltransferase 1 (AgOMT1), an enzyme that can convert 6- and 2-hydroxymyristicin to dillapiole and apiole, respectively, via the methylation of the ortho-hydroxy group. The AgOMT1 protein shows an apparent Km value of 3.5 µm for 6-hydroxymyristicin and is 75% identical to the anise (Pimpinella anisum) O-methyltransferase (PaAIMT1) that can convert isoeugenol to methylisoeugenol via methylation of the hydroxy group at the para-position of the benzene ring. AgOMT1 showed a preference for 6-hydroxymyristicin, whereas PaAIMT1 displayed a large preference for isoeugenol. In vitro mutagenesis experiments demonstrated that substituting only a few residues can substantially affect the substrate specificity of these enzymes. Other plants belonging to the Apiaceae family contained homologous O-methyltransferase (OMT) proteins highly similar to AgOMT1, converting 6-hydroxymyristicin to dillapiole. Our results indicate that apiaceous phenylpropene OMTs with ortho-methylating activity evolved independently of phenylpropene OMTs of other plants and the enzymatic function of AgOMT1 and PaAIMT1 diverged recently.

Development, validation and application of a gas chromatography method for the determination of dillapiole from Piper aduncum essential oil in skin permeation samples.

The essential oil extracted from the leaves of Piper aduncum has antifungal, insecticidal and antibacterial activity. Studies with its main compound, dillapiole (DIL) revealed antibacterial and anti-inflammatory potential. Despite all this bioactivity, there is no updated report on the development and validation of analytical and bioanalytical methodology to quantify DIL in skin samples. A selective, precise, accurate and adequate method for the determination of DIL in solutions, porcine ear skin samples and receptor fluid was developed and validated by headspace extraction-gas chromatography with flame ionization detection (HS-GC-FID). HS-GC-FID was applied to determine DIL in Franz cell permeation and retention studies using porcine ear skin samples. In the HS-GC-FID method, matrix-related interferences were not observed at the peak of the DIL retention time. The results showed a high recovery (>97%) after the extraction procedure, allowing the quantification of DIL in complex matrices. In vitro permeation/retention for DIL showed cumulative amounts permeated in the order: receptor fluid (21.98 ± 1.19 µg/cm2 ) > epidermis (15.40 ± 1.20 µg/cm2 ) > dermis (9.52 ± 1.13 µg/cm2 ). HS-GC-FID was successfully validated and the results point to DIL transdermal permeation and to the potential to develop pharmaceutical formulations for skin delivery to treat inflammation or infections.

Isolation, screening and identification of key components having intense insect repellent activity against Plodia interpunctella from four different medicinal plant materials.

BACKGROUND: Global warming and the indiscriminate use of pesticides have increased the propagation of the stored-product insect pests, leading to enormous losses in the agriculture and food industries. The most used insect repellents are synthetic derivatives; however, these have an adverse effect on human health as well as on the environment. Therefore, we attempted to find materials with insect repellent activity in natural products. The present study aimed to identify the single chemical component with intense insect repellent activity in extracts from four different Oriental medicinal plant materials: (i) Anethum graveolens L. (dill) seeds; (ii) Artemisia capillaris Thunb. (capillary wormwood) leaves; (iii) smoked Prunus mume Siebold & Zucc. (mume) fruits; and (iv) Rhus javanica L. (galls). RESULTS: As a result of the bioassay-guided fractionation of each extract against the Plodia interpunctella, stored-product insect, the n-hexane fraction of dill seeds extract was confirmed as the optimal fraction between all of the fractions. In total, 32 chemical components were identified from the n-hexane fraction of dill seeds by gas chromatography-mass spectrometry analysis, and the two main components were dillapiole (47.51%) and carvone (26.76%). Of the two components, dillapiole was confirmed as the key component playing an essential role in insect repellent activity. CONCLUSION: Our study suggests that dillapiole has the potential to be used as a natural insect repellent for the control of P. interpunctella infestation in agricultural and food products during distribution and storage. © 2021 Society of Chemical Industry.

Dillapiole in Piper holtonii as an Inhibitor of the Symbiotic Fungus Leucoagaricus gongylophorus of Leaf-Cutting Ants.

Plants of the Piperaceae family are studied for their diverse secondary metabolism with a vast array of compounds that act as chemical defense agents against herbivores. Of all the agricultural pests, the management of insects is a highly significant challenge in the Neotropics, and ants of the Attini tribe pose a major problem. Due to their symbiotic association with the fungus Leucoagaricus gongylophorus (Möller) Singer (Agaricaceae), the species of Atta and Acromyrmex have exhaustive foraging activity which has intensified as deforestation and monoculture farming have increased. The control of leaf-cutting ants is still carried out with synthetic products with negative consequences to the environment and human health. In search for natural and sustainable alternatives to synthetic pesticides, Piper holtonii C. DC. was selected among other plant species after field observations of the foraging activity of Atta cephalotes, which revealed that P. holtonii was never chosen by ants. In vitro evaluation of an ethanol extract of the leaves of P. holtonii resulted in promising inhibitory activity (IC50 102 ppm) against L. gongylophorus. Subsequently, bioassay-guided fractionation led to the isolation of the phenylpropanoid dillapiole, which was also detected in the essential oil. This compound demonstrated inhibition of the fungus with an IC50 of 38 ppm. Considering the symbiotic relationship between the Attini ants and L. gongylophorus, the negative effect on the survival of one of the organisms will affect the survival of the other, so dillapiole or standardized essential oil extracts of P. holtonii containing this active principle could be a unique and useful source as a control agent for leaf cutting-ants.

Apoptotic effects of dillapiole on maturation of mouse oocytes, fertilization and fetal development.

Previously, we reported that dillapiole, a phenylpropanoid with antileishmanial, anti-inflammatory, antifungal and acaricidal activities, is a risk factor for normal embryonic development that triggers apoptotic processes in the inner cell mass of mouse blastocysts, leading to impaired embryonic development and cell viability. In the current study, we investigated the deleterious effects of dillapiole on mouse oocyte maturation, in vitro fertilization (IVF) and subsequent pre- and post-implantation development, both in vitro and in vivo. Notably, dillapiole induced significant impairment of mouse oocyte maturation, decrease in the IVF rate and inhibition of subsequent embryonic development in vitro. Pre-incubation of oocytes with dillapiole during in vitro maturation led to an increase in post-implantation embryo resorption and decrease in mouse fetal weight. In an in vivo animal model, 2.5, 5 or 10 µM dillapiole provided in drinking water caused a decrease in oocyte maturation and IVF, and led to deleterious effects on early embryonic development. Importantly, pre-incubation of oocytes with a caspase-3-specific inhibitor effectively blocked dillapiole-triggered deleterious effects, clearly implying that embryonic injury induced by dillapiole is mediated via a caspase-dependent apoptotic mechanism. To the best of our knowledge, this is the first study to establish the impact of dillapiole on maturation of mouse oocytes, fertilization and sequential embryonic development.

PPAR gamma agonistic activity of dillapiole: protective effects against diabetic nephropathy.

Using structural similarity approach we identified dillapiole, a phenylpropanoid, the main component of Piper aduncum L. and Anethum graveolens L. essential oils as potential PPARγ agonist. Molecular docking revealed that dillapiole binds to the active site of PPARγ, similar to pioglitazone binding. In silico ADME studies showed that dillapiole has high water solubility and GI absorption. Dillapiole was also observed to be partial agonist of PPARγ receptors with EC50 of 43.95 µM. In BHK-21 cells cultured under hyperglycaemic conditions, dillapiole administration reduced oxidative stress and prevented decrease in histone H3 acetylation (k9/14) levels. In HFD + STZ induced diabetic mice, dillapiole treatment for 7 days was able to improve renal functions and decrease plasma glucose level to 138.39 ± 12.36 mg/dl along with decreasing total cholesterol (29%), triglycerides (48.8%), LDL (24.7%), and VLDL (65%) levels in serum. These results show that dillapiole is a potential PPARγ-agonist and thus needs to explore further.

Structural and Functional Characterization of Medicinal Plants as Selective Antibodies towards Therapy of COVID-19 Symptoms.

Considering the COVID-19 pandemic, this research aims to investigate some herbs as probable therapies for this disease. Achillea millefolium (Yarrow), Alkanet, Rumex patientia (Patience dock), Dill, Tarragon, and sweet fennel, including some principal chemical compounds of achillin, alkannin, cuminaldehyde, dillapiole, estragole, and fenchone have been selected. The possible roles of these medicinal plants in COVID-19 treatment have been investigated through quantum sensing methods. The formation of hydrogen bonding between the principal substances selected in anti-COVID natural drugs and Tyr-Met-His (the database amino acids fragment), as the active area of the COVID protein, has been evaluated. The physical and chemical attributes of nuclear magnetic resonance, vibrational frequency, the highest occupied molecular orbital energy and the lowest unoccupied molecular orbital energy, partial charges, and spin density have been investigated using the DFT/TD-DFT method and 6-311+G (2d,p) basis set by the Gaussian 16 revision C.01 program toward the industry of drug design. This research has exhibited that there is relative agreement among the results that these medicinal plants could be efficient against COVID-19 symptoms.

Composition and Biological Activity of the Essential Oils from Wild Horsemint, Yarrow, and Yampah from Subalpine Meadows in Southwestern Montana: Immunomodulatory Activity of Dillapiole.

Agastache urticifolia (Benth.) Kuntze (horsemint), Achillea millefolium L. (yarrow), and Perideridia gairdneri (Hook. & Arn.) Mathias (yampah) are native, culturally important plants that grow in the subalpine meadows of Montana. Analysis of the composition of essential oils extracted from these plants showed that the main components of essential oils obtained from flowers and leaves of A. urticifolia (designated as AUF/AUL) were menthone (2.7/25.7%), isomenthone (2.6/29.1%), pulegone (78.9/28.8%), and limonene (4.2/6.2%), whereas essential oils obtained from the inflorescence of A. millefolium (designated as AMI) were high in α-thujone (17.1%) and ß-thujone (14.9%), 1,8-cineole (17.0%), camphor (13.0%), sabinene (7.0%), guaia-3,9-dien-11-ol (3.2%), and terpinen-4-ol (2.5%). Essential oils obtained from the inflorescence of P. gairdneri (designated as PGI) contained high amounts of dillapiole (30.3%), p-cymen-8-ol (14.1%), terpinolene (12.0%), 4-hydroxy-4-methyl-cyclohex-2-enone (6.2%), and γ-terpinene (2.4%). Evaluation of their immunomodulatory activity demonstrated that essential oils extracted from all of these plants could activate human neutrophils with varying efficacy. Analysis of individual components showed that dillapiole activated human neutrophil intracellular Ca2+ flux ([Ca2+]i) (EC50 = 19.3 ± 1.4 µM), while α-thujone, ß-thujone, menthone, isomenthone, and pulegone were inactive. Since dillapiole activated neutrophils, we also evaluated if it was able to down-regulate neutrophil responses to subsequent agonist activation and found that pretreatment with dillapiole inhibited neutrophil activation by the chemoattractant fMLF (IC50 = 34.3 ± 2.1 µM). Pretreatment with P. gairdneri essential oil or dillapiole also inhibited neutrophil chemotaxis induced by fMLF, suggesting these treatments could down-regulate human neutrophil responses to inflammatory chemoattractants. Thus, dillapiole may be a novel modulator of human neutrophil function.

Piper aduncum Essential Oil Rich in Dillapiole: Development of Hydrogel-Thickened Nanoemulsion and Nanostructured Lipid Carrier Intended for Skin Delivery.

The essential oil extracted from the leaves of Piper aduncum, an aromatic plant from the Amazon region, is rich in dillapiole and presents anti-inflammatory activity. In this study, nanoemulsions (NE) and nanostructured lipid carriers (NLC), which are biocompatible nanostructured systems of a lipid nature, were prepared by high-pressure homogenization for the yet unexplored skin delivery of dillapiole. The addition of hydroxyethylcellulose produced hydrogel-thickened NE or NLC in view to improving the viscosity and skin adherence of the nanoformulations. Formulations were characterized with respect to dillapiole content, droplet size, polydispersity index, zeta potential, morphology, rheological behavior, bioadhesion, skin permeation profile, and in vitro irritancy (HET-CAM). The formulations developed presented spherical, homogeneous nanometric particle size (around 130 nm), narrow polydispersity index (<0.3), and negative zeta potential (around −40 mV). Dillapiole content was slightly lower in NLC compared to NE since the production process involves heating. The hydrogels containing nanocarriers showed pseudoplastic behavior with bioadhesive characteristics. The developed formulations exhibited a controlled release profile, dillapiole delivery up to the dermis, the layer of interest for anti-inflammatory potential, and low irritant potential in the chorioallantoic membrane (HET-CAM). Both hydrogels-thickened NE and NLC seemed to be promising formulations for skin delivery of Piper aduncum essential oil.

Safety and efficacy of a feed additive consisting of an essential oil from the fruit of Cuminum cyminum L. (cumin oil) for use in all animal species (FEFANA asbl).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of an essential oil obtained from the fruit of Cuminum cyminum L. (cumin oil), when used as a sensory additive in feed and water for drinking for all animal species. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the use of cumin oil up to the maximum proposed use levels in feed of 15 mg/kg complete feed is considered as safe for all animal species. The FEEDAP Panel considered the use in water for drinking as safe provided that the total daily intake of the additive does not exceed the daily amount that is considered safe when consumed via feed. No concerns for consumers were identified following the use of cumin oil up to the maximum proposed use level in feed. The additive under assessment should be considered as irritant to skin and eyes, and as a dermal and respiratory sensitiser. When handling the essential oil, exposure of unprotected users to estragole (and dillapiole) cannot be excluded. Therefore, to reduce the risk, the exposure of the users should be minimised. The use of cumin oil at the proposed use level in feed is not expected to pose a risk to the environment. Since C. cyminum and its preparations are recognised to flavour food and its function in feed would be essentially the same as that in food, no further demonstration of efficacy is considered necessary.

Piper aduncum essential oil: a promising insecticide, acaricide and antiparasitic. A review.

Several studies have assessed the potential of essential oils as substitutes for synthetic pesticides, in order to counter insect resistance to commercial pesticides. Piper aduncum L. is a very common shrub in the Amazon Rainforest and in other subtropical areas. The objective of this review was to analyse the existing information on P. aduncum essential oil as a raw material for new bioproducts for sustainable pest disease management. With this review, we collected and critically analysed 59 papers, representing all the studies that aimed to evaluate the essential oil properties of this species as an insecticide, acaricide and antiparasitic. The chemical composition differs depending on the origin, although phenylpropanoid dillapiole is the most cited component, followed by myristicin, 1,8-cineole and ß-ocimene. Between the acaricidal, antiparasitic and synergistic activities, the insecticidal effects are highly promising, with optimal results against the malaria vector Aedes aegypti, with an LC50 that ranges between 57 and 200µg/mL. Acaricidal activity has mainly been reported against Tetranychus urticae, showing an LC50 that ranges between 5.83 and 7.17µg/mL. Antiparasitic activity has predominately been found on Leishmania amazonensis, and antipromastigote activity has been found to be between 23.8 and 25.9µg/mL. Concerning the synergistic effect between dillapiole and synthetic insecticides, four studies on Spodoptera frugiperda found promising results with cypermethrin. In this review, we highlighted the potential of P. aduncum essential oil as a biopesticide, also focusing on the lack of information about applied research. We also provide suggestions for future investigations.

TITLE: L'huile essentielle de Piper aduncum: un insecticide, acaricide et antiparasitaire prometteur. Une synthèse. ABSTRACT: Plusieurs études ont abordé le potentiel des huiles essentielles comme substitut aux pesticides de synthèse, afin de lutter contre la résistance des insectes aux pesticides commerciaux. Piper aduncum L. est un arbuste très commun dans la forêt amazonienne et dans d'autres zones subtropicales. L'objectif de ce travail est d'analyser les informations existantes sur l'huile essentielle de P. aduncum comme matière première de nouveaux bioproduits pour une gestion durable des maladies nuisibles. Dans cette synthèse, nous avons collecté et analysé de manière critique 59 articles, représentant toutes les études qui visaient à prouver les propriétés des huiles essentielles de cette espèce en tant qu'insecticide, acaricide et antiparasitaire. La composition chimique diffère selon la provenance, bien que le phénylpropanoïde dillapiole soit le composant le plus cité, suivi de la myristicine, du 1,8-cinéole et du ß-ocimène. À côté des activités acaricide, antiparasitaire et de synergie avec les autres composants, les effets insecticides sont les plus prometteurs, avec des résultats optimaux contre le vecteur du paludisme Aedes aegypti, avec une CL50 comprise entre 57 et 200µg/mL. Une activité acaricide a été principalement rapportée contre Tetranychus urticae avec une CL50 comprise entre 5,83 et 7,17µg/mL. L'activité antiparasitaire a été montrée principalement sur Leishmania amazonensis et l'activité antipromastigote s'est avérée être comprise entre 23,8 et 25,9µg/mL. Concernant l'effet synergique entre le dillapiole et les insecticides synthétiques, quatre études sur Spodoptera frugiperda ont mis l'accent sur des résultats prometteurs avec la cyperméthrine. Avec cette étude, nous avons mis en évidence le potentiel de l'huile essentielle de P. aduncum en tant que biopesticide, en insistant sur le manque d'informations de la recherche appliquée et sur certaines propositions pour de futures recherches.

Effects of inoculation by arbuscular mycorrhizal fungi on the composition of the essential oil, plant growth, and lipoxygenase activity of Piper aduncum L.

The aim of this study was to evaluate the changes in the production of secondary metabolites Piper aduncum seedlings were inoculated by spores of the arbuscular mycorrhizal fungi (AMF) Rhizophagus clarus and Claroideoglomus etunicatum. P. aduncum seedlings were inoculated by spores of R. clarus and C. etunicatum and then, development parameters, root colonization, lipoxygenase (LOX) activity, and essential oil (OE) chemical composition were monitored at 30, 60 and 90 days' post-inoculation (dpi). The inoculation had influenced the plant height and root length at 30 and 90 dpi and microscopic analysis of roots showed the presence of hyphae, arbuscules and vesicles in the inoculated plants. Phenylpropanoids and sesquiterpene hydrocarbons were the main compounds in the EO. In the leaves, the concentration of phenylpropanoids showed a decrease, mainly at 60 dpi, with increased sesquiterpene hydrocarbon production. The main compounds were dillapiole, myristicin, and germacrene D; the dillapiole concentration decreased in all treatments. LOX activity had an increase in the leaves and roots at 90 dpi. These results suggest that alterations in the secondary metabolites of P. aduncum can be induced by its mechanisms of resistance during AMF interaction.

Comparative essential oil composition of flowers, leavesand stems of basil (Ocimum basilicum L.) used as herb.

The chemical composition of flower, leaves and stems from basil (Ocimum basilicum L.) have been examined by GC and GC-MS. The identified components constituting 99.03%, 95.04% and 97.66% of the flower, leaves and stem oils, respectively. The main constituents of the essential oil of flower, leaves and stem oils, respectively, were estragole (58.26%, 52.60% and 15.91%) and limonene (19.41%, 13.64% and 2.40%) and p-cymene (0.38%, 2.32% and 2.40%). Dill apiole (50.07%) was identified as the highest main constituent for stem. Estragole (15.91%), apiole (9.48) and exo-fenchyle acetate (6.14%) followed in order to decreasing them. Minor qualitative and major quantitative variations for some compounds of essential oils were determined with respect to different parts of O. basilicum. It was reported that the chemical composition of different parts oils of basil are very variable. It is known that specific estragole chemotypes are also known.

Toxic effect and genotoxicity of the semisynthetic derivatives dillapiole ethyl ether and dillapiole n-butyl ether for control of Aedes albopictus (Diptera: Culicidae).

Two derivatives of dillapiole, dillapiole ethyl ether (1KL39-B) and butyl ether-n dillapiole (1KL43-C), were studied for their toxicity and genotoxicity against Aedes albopictus, to help develop new strategies for the control of this potential vector of dengue and other arboviruses, because it is resistant to synthetic insecticides. Eggs and larvae exposed to different concentrations of 1KL39-B (25, 30, 50, 70, and 80µg/mL) and of 1KL43-C (12.5, 20, 25, 30 and 40µg/mL) exhibited toxicity and susceptibility, with 100% mortality. The LC50 was 55.86±1.57µg/mL for 1KL39-B and 25.60±1.24µg/mL for 1KL43-C, while the LC90 was 70.12µg/mL for 1KL39-B and 41.51µg/mL for 1KL43-C. The gradual decrease in oviposition of the females of the G1 to G4 generations was proportional to the increase in concentrations of these compounds, which could be related to the cumulative effect of cell anomalies in neuroblasts and oocytes (P<0.05), including micronuclei, budding, multinucleated cells and nuclear bridges. These findings showed that both 1KL39-B and 1KL43-C can serve as potential alternatives in the control of A. albopictus.

Genotoxic Effects of Semi-Synthetic Isodillapiole on Oviposition in Aedes aegypti (Linnaeus, 1762) (Diptera: Culicidae)

Abstract INTRODUCTION: Semi-synthetic dillapiole compounds derived from Piper aduncum essential oil are used as alternative insecticides to control insecticide-resistant Aedes aegypti. Thus, we aimed to evaluate the genotoxic effects of semi-synthetic isodillapiole on the nuclei of neuroblasts (larvae) and oocytes (females) and the mean oviposition rates of the females over four generations (G1, G2, G3, and G4) of Ae. aegypti. METHODS: Larvae were captured in the city of Manaus, Amazonas state, Brazil, and exposed to isodillapiole in bioassays (20, 40, and 60 µg/mL) and a negative control (0.05% DMSO in tap water) for 4 h. The cerebral ganglia were extracted from the larvae and oocytes from the adult females to prepare slides for cytogenetic analysis. Breeding pairs were established and eggs counts were quantified taken after the bioassays. RESULTS: The analysis of 20,000 interphase nuclei of neuroblasts and oocytes indicated significant genotoxicity (micronuclei, budding, polynucleated cells, and other malformations) compared to that of the control. Metaphasic and anaphasic nuclei presented chromosomal breaks; however, no significant variation and damage was observed in the negative control. A significant reduction in mean oviposition rates was also recorded following exposure to isodillapiole over the four generations (G1, G2, G3, and G4). CONCLUSIONS: The toxic and genotoxic effects of isodillapiole on Ae. aegypti were caused by reduced oviposition in the females and nuclear abnormalities over the four generations of the trials. Further studies are required, rather than our in vitro assays, to verify the efficacy of exposure to this compound for controlling Ae. aegypti.

Age-dependent changes from allylphenol to prenylated benzoic acid production in Piper gaudichaudianum Kunth.

HPLC-DAD and principal component analysis (PCA) of the (1)H NMR spectrum of crude plant extracts showed high chemical variability among seedlings and adult organs of Piper gaudichaudianum. While gaudichaudianic acid was the major compound in the adult leaves, apiole and dillapiole were the major compounds in their seedling leaves. By the 15th month of seedling growth, the levels of apiole and dillapiole decreased and gaudichaudianic acid appeared along with two compounds, biosynthetically related to gaudichaudianic acid.

Cytotoxic effects of dillapiole on MDA-MB-231 cells involve the induction of apoptosis through the mitochondrial pathway by inducing an oxidative stress while altering the cytoskeleton network.

Breast cancer is the world's leading cause of death among women. This situation imposes an urgent development of more selective and less toxic agents. The use of natural molecular fingerprints as sources for new bioactive chemical entities has proven to be a quite promising and efficient method. Here, we have demonstrated for the first time that dillapiole has broad cytotoxic effects against a variety tumor cells. For instance, we found that it can act as a pro-oxidant compound through the induction of reactive oxygen species (ROS) release in MDA-MB-231 cells. We also demonstrated that dillapiole exhibits anti-proliferative properties, arresting cells at the G0/G1 phase and its antimigration effects can be associated with the disruption of actin filaments, which in turn can prevent tumor cell proliferation. Molecular modeling studies corroborated the biological findings and suggested that dillapiole may present a good pharmacokinetic profile, mainly because its hydrophobic character, which can facilitate its diffusion through tumor cell membranes. All these findings support the fact that dillapiole is a promising anticancer agent.

First phytochemical description of essential oils from Piper cachimboense (Piperales, Piperaceae) / Primeira descrição fitoquímica de óleos essenciais de Piper cachimboense (Piperales, Piperaceae)

Piper cachimboense is recorded only for the Amazon region of Brazil and Colombia, and the objective of this study was to report the first phytochemical assessment of the composition of the essential oils (EOs) from this species collected in the Amazon rainforest, in Novo Progresso, Pará State, Brazil. Samples of leaves were subjected to hydrodistillation in a Clevenger-type apparatus. The chemical identification was carried out by gas chromatography. The yield of oils was of 11.03 ± 5.94% for fresh leaves, and 1.07 ± 0.27% for dry leaves. The analysis showed 36 volatile compounds from fresh leaves and 49 from dried leaves. Main constituents in EOs of both fresh and dried leaves from P. cachimboense were (E)-caryophyllene, germacrene-D, -amorfene, -cadinene and apiole.

Piper cachimboense é registrada apenas para a região amazônica do Brasil e Colômbia, e o objetivo deste estudo foi relatar, pela primeira vez, a composição fitoquímica dos óleos essenciais (OEs) desta espécie coletada na floresta amazônica, em Novo Progresso/PA, Brasil. Amostras de folhas foram submetidas a hidrodestilação em aparelho tipo Clevenger. A identificação química foi realizada por cromatografia gasosa e o rendimento dos óleos foi de 11,03 ± 5,94% para as folhas frescas e de 1,07 ± 0,27% para as folhas secas. A análise mostrou 36 compostos voláteis para folhas frescas e 49 para folhas secas. Os constituintes principais dos OEs de folhas frescas e secas de P. cachimboense foram (E)-cariofileno, germacreno-D, -amorfeno, -cadineno e apiol.

Piper aduncum against Haemonchus contortus isolates: cross resistance and the research of natural bioactive compounds / Piper aduncum contra isolados de Haemonchus contortus: resistência cruzada e a pesquisa de bioativos naturais

Abstract The anthelminthic activity of the essential oil (EO) of Piper aduncum L. was tested in vitro on eggs and larvae of resistant (Embrapa2010) and susceptible (McMaster) isolates of Haemonchus contortus. The EO was obtained by steam distillation and its components identified by chromatography. EO concentrations of 12.5 to 0.02 mg/mL were used in the egg hatch test (EHT) and concentrations of 3.12 to 0.01 mg/mL in the larval development test (LDT). Inhibition concentrations (IC) were determined by the SAS Probit procedure, and significant differences assessed by ANOVA followed by Tukey’s test. In the EHT, the IC50 for the susceptible isolate was 5.72 mg/mL. In the LDT, the IC50 and IC90 were, respectively, 0.10 mg/mL and 0.34 mg/mL for the susceptible isolate, and 0.22 mg/mL and 0.51 mg/mL for the resistant isolate. The EO (dillapiole 76.2%) was highly efficacious on phase L1. Due to the higher ICs obtained for the resistant isolate, it was raised the hypothesis that dillapiole may have a mechanism of action that resembles those of other anthelmintic compounds. We further review and discuss studies, especially those conducted in Brazil, that quantified the major constituents of P. aduncum-derived EO.

Resumo Este estudo avaliou a atividade anti-helmíntica in vitro do óleo essencial (OE) de Piper aduncum L. sobre ovos e larvas de Haemonchus contortus, verificando se um isolado resistente (Embrapa2010), apresentaria o mesmo comportamento que um sensível (McMaster). O OE foi obtido por arraste a vapor e analisado por cromatografia para identificação dos constituintes. O óleo foi avaliado nas concentrações de 12,5 a 0,02 mg/mL no Teste de eclosão dos ovos (TEO) e nas concentrações de 3,12 a 0,01 mg/mL no Teste de desenvolvimento larvar (TDL). As concentrações inibitórias (CI) foram determinadas pelo procedimento Probit do SAS e as diferenças estatísticas geradas pela ANOVA seguida pelo teste de Tukey. Para o isolado sensível obteve-se CI50 de 5,72 mg/mL no TEO. No TDL o óleo apresentou CI50 e CI90 de 0,10 mg/mL e 0,34 mg/mL para o isolado sensível e 0,22 mg/mL e 0,51 mg/mL para o resistente, respectivamente. Demonstrou-se que o OE (dilapiol 76,2%) teve alta eficácia sobre a fase L1. Devido às elevadas CIs obtidas para o isolado resistente, levantou-se a hipótese de que o dilapiol talvez possua um mecanismo de ação semelhante a algum grupo anti-helmíntico. O artigo faz uma revisão e discute estudos de quantificação dos constituintes majoritários do OE de P. aduncum, destacando os realizados no Brasil.

Antibacterial activity of the Piper aduncum oil and dillapiole, its main constituent, against multidrug-resistant strains / Actividad antibacteriana del aceite de Piper aduncum y dillapiole, su componente principal, frente a cepas resistentes a múltiples fármacos

The study aimed to evaluate the bactericidal activity of oil essential and dillapiole from P. aduncum against standard and multidrug-resistant strains of Staphylococcus spp. The oil showed antimicrobial action against these strains, but better results were obtained for the standards strains of S. epidermidis and S. aureus, with MIC of 250 and 500 ug/mL, respectively. Dillapiolle was less effective than the oil against the same standard and multi-drug resistant strains (MIC =1000 ug/mL). However, when dillapiolle was tested in combination with myristicin, another component of the oil, it increased its bactericidal activity and showed a synergistic action...

El objetivo del estudio fue evaluar la actividad bactericida de los aceites esenciales y dillapiole de P. aduncum contra cepas estándar y multirresistentes de Staphylococcus spp. El aceite mostró acción antimicrobiana frente a estas cepas, pero se obtuvo mejores resultados para las cepas de S. epidermidis y S. aureus, con MIC de 250 y 500 ug/ml, respectivamente. Dillapiolle fue menos eficaz que el aceite contra cepas estándar y multirresistentes (MIC = 1000 ug/ml). Sin embargo, cuando dillapiolle fue probado en combinación con la miristicina, otro componente del aceite, que aumentó su actividad bactericida y mostró una acción sinérgica...