Cytotoxic, acute oral toxicity, genotoxic and mutagenic assessment of the essential oil from fresh leaves of Croton argyrophyllus (Kunth.).

ETHNOPHARMACOLOGICAL RELEVANCE: Croton argyrophyllus Kunth., commonly known as "marmeleiro" or "cassetinga," is widely distributed in the Brazilian Northeast region. Its leaves and flowers are used in traditional medicine as tranquilizers to treat flu and headaches. AIM OF THE STUDY: This study was conducted to determine the chemical composition and toxicological safety of essential oil from C. argyrophyllus leaves using in vitro and in vivo models. MATERIALS AND METHODS: The chemical composition of the essential oil was determined using a gas chromatograph coupled to a mass spectrometer. Cytotoxicity was tested in the HeLa, HT-29, and MCF-7 cell lines derived from human cells (Homo sapiens) and Vero cell lines derived from monkeys (Cercopithecus aethiops) using the MTT method. Acute toxicity, genotoxicity. Mutagenicity tests were performed in Swiss mice (Mus musculus), which were administered essential oil orally in a single dose of 2000 mg/kg by gavage. RESULTS: The main components of the essential oil were p-mentha-2-en-1-ol, α-terpineol, ß-caryophyllene, and ß-elemene. The essential oil exhibited more than 90% cytotoxicity in all cell lines tested. No deaths or behavioral, hematological, or biochemical changes were observed in mice, revealing no acute toxicity. In genotoxic and mutagenic analyses, there was no increase in micronuclei in polychromatic erythrocytes or in the damage and index in the comet assay. CONCLUSIONS: The essential oil was cytotoxic towards the tested cell lines but did not exert toxic effects or promote DNA damage when administered orally at a single dose of 2000 mg/kg in mice.

Critical assessment of the endocrine potential of Linalool and Linalyl acetate: proactive testing strategy assessing estrogenic and androgenic activity of Lavender oil main components.

The acyclic linear monoterpenes Linalool (Lin) and Linalyl acetate (LinAc) occur in nature as major constituents of various essential oils such as lavender oils. A potential endocrine activity of these compounds was discussed in literature including premature thelarche and prepubertal gynecomastia due to lavender product use. This study aims to follow-up on these critical findings reported by testing Lin and LinAc in several studies in line with current guidance and regulatory framework. No relevant anti-/ER and AR-mediated activity was observed in recombinant yeast cell-based screening tests and guideline reporter gene in vitro assays in mammalian cells. Findings in the screening test suggested an anti-androgenic activity, which could not be confirmed in the respective mammalian cell guideline assay. Mechanistic guideline in vivo studies (Uterotrophic and Hershberger assays) with Lin did not show significant dose related changes in estrogen or androgen sensitive organ weights and a guideline reproductive toxicity screening study did not reveal evident effects on sex steroid hormone sensitive organ weights, associated histopathological findings and altered sperm parameters. Estrous cycling and mating/fertility indices were not affected and no evident Lin-related steroid hormone dependent effects were found in the offspring. Overall, the initial concerns from literature were not confirmed. Findings in the yeast screening test were aberrant from follow-up guideline in vitro and in vivo studies, which underlines the need to apply careful interpretation of single in vitro test results to support a respective line of evidence and to establish a biologically plausible link to an adverse outcome.

Predictive toxicological effects of Artemisia absinthium essential oil on hepatic stellate cells.

Medicinal plants are important worldwide, considering their properties for treating diseases; however, few studies have evaluated their toxicological potential. Among them, Artemisia absinthium is frequently used to treat liver diseases, because its essential oil has several popular therapeutic properties. Based on this information, in the present study, we investigated molecular connectors of physiological effects of the Artemisia absinthium essential oil on human hepatic stellate cell line, LX-2, to explore the potential toxicity of the plant on liver cells. LX-2 is a cellular model to investigate mechanisms of liver fibrosis; then, to analyze the essential oil effects LX-2 was cultured under different conditions, treated or not with the essential oil at 0.4 µg/µL for 24 h. Next, fluorescence microscopy analyses, gene expression measurements, and biochemical approaches revealed that the essential oil reduced pro-fibrogenic markers; however, disrupt lipid metabolism, and cause cellular stress, by the activation of cellular detoxification and pro-inflammatory processes. In conclusion, the hepatic stellate cells incubated with the essential oil present an antifibrotic potential, supporting its popular use; however, the combined results suggest that the essential oil of Artemisia absinthium should be used with caution.

Antiedema and antinociceptive potential of the essential oil of Pectis elongata Kunt (Asteraceae) from the Brazilian Amazon.

ETHNOPHARMACOLOGICAL RELEVANCE: Pectis elongata, a herbaceous species that is known in northern Brazil as "cominho" or "limãozinho", is traditionally used in the region for the treatment of fevers, colds, hypotension, genitourinary and gastric disorders, and pain. AIM OF THE STUDY: Determine the chemical composition and acute oral toxicity and evaluate whether Pectis elongata essential oil (PeEO) has antiedema and antinociceptive activity. MATERIALS AND METHODS: The chemical composition was determined using gas chromatography coupled to mass spectrometry (GC/MS) and the degree of toxicity determined by the LD50. The antiedema and antinociceptive potential was evaluated via the λ-carrageenan-induced paw edema test and formalin test, respectively. RESULTS: Citral (geranial and neral) was characterized as a major component of the PeEO, representing 89% of the total identified compounds. According to OECD criteria (2002), the EO was considered non-toxic since it presented LD50 values over 2000 mg kg-1. Its antiedema potential was observed at doses of 200 and 400 mg kg-1 (p ≤ 0.05). At a dose of 400 mg kg-1, PeEO also showed antinociceptive potential (p ≤ 0.05), both in the neurogenic phase and in the inflammatory phase. CONCLUSIONS: PeEO, which is rich in citral, did not induce any characteristic signs of acute oral toxicity and was also efficient in reducing carrageenan-induced paw edema, in addition to presenting antinociceptive potential and acting on both central and peripheral pain. It is thus a promising candidate for the development of a new herbal medicine with anti-inflammatory and analgesic action.

Evaluation of 28-day repeated doses oral toxicity of essential oil from Psidium glaziovianum Kiaersk leaves on various biological parameters in Swiss mice.

Only a small number of the many medicinally important species in the genus Psidium L. have had their safety assessed. Psidium glaziovianum, a plant native to Brazil, is reported to exert antinociceptive and anti-inflammatory effects; however, there are no apparent reports of long-term safety following administering of repeated doses. The aim of this study was to examine the effects of 28-day oral of treatment at 250, 500 or 1,000 mg/kg Psidium glaziovianum essential oil (PgEO) on behavioral and physiological parameters in male and female Swiss mice. First, PgEO was chemically characterized by gas chromatography mass spectrometry (GC-MS). The following parameters were examined: motor activity, body temperature, blood glucose, urine, hematology, biochemistry, histology, and oxidative stress. Characterization of PgEO revealed 48 components which were dominated by sesquiterpenes 1,8-cineol (24.29%), α-pinene (19.73%) and ß-pinene (17.31%). Data showed that PgEO treatment in mice increased activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) without markedly affecting body weight, hematological or biochemical parameters, as well as water or food consumption. Administration of PgEO in repeated daily dosages over 28 days did not significantly alter exploratory or locomotor activities. Based upon our findings, PgEO administration daily for 28 days, exhibited low toxicity and absence of effects on the nervous system. Data demonstrated that PgEO produced hypoglycemic and antioxidant actions which need to be considered in safety assessment.

Silicon dioxide nanoparticles suppress copper toxicity in Mentha arvensis L. by adjusting ROS homeostasis and antioxidant defense system and improving essential oil production.

Copper (Cu) is an essential micronutrient for plants; however, the excessive accumulation of Cu due to various anthropogenic activities generates progressive pollution of agricultural land and that causes a major constraint for crop production. Excess Cu (80 mg kg-1) in the soil diminished growth and biomass, photosynthetic efficiency and essential oil (EO) content in Mentha arvensis L., while amplifying the antioxidant enzyme's function and reactive oxygen species (ROS) production. Therefore, there is a pressing need to explore effective approaches to overcome Cu toxicity in M. arvensis plants. Thus, the present study unveils the potential of foliar supplementation of two distinct forms of silicon dioxide nanoparticles (SiO2 NPs) i.e., Aerosil 200F and Aerosil 300 to confer Cu stress tolerance attributes to M. arvensis. The experiment demonstrated that applied forms of SiO2 NPs (120 mg L-1), enhanced plants' growth and augmented the photosynthetic efficiency along with the activities of CA (carbonic anhydrase) and NR (nitrate reductase), however, the effects were more accentuated by Aerosil 200F application. Supplementation of SiO2 NPs also exhibited a beneficial effect on the antioxidant machinery of Cu-disturbed plants by raising the level of proline and total phenol as well as the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), ascorbate peroxidase (APX) and glutathione reductase (GR), thereby lowering ROS and electrolytic leakage (EL). Interestingly, SiO2 NPs supplementation upscaled EO production in Cu-stressed plants with more pronounced effects received in the case of Aerosil 200F over Aerosil 300. We concluded that the nano form (Aerosil 200F) of SiO2 proved to be the best in improving the Cu-stress tolerance in plants.

Antinociceptive and anti-inflammatory activities of essential oil of the leaves of Amburana cearensis (Allemão) A.C. Smith. from the semi-arid region of Northeastern Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: Amburana cearensis (Allemão) A.C. Smith is a medicinal plant with wide distribution in South America, popularly known in Brazil as "cumaru" or "amburana de cheiro". In folk medicine, in the semi-arid region of Northeastern Brazil, infusions, teas and decoctions of leaves of Amburana cearensis have their practical use for treating fever, gastrointestinal disorders, inflammation, and inflammation pain. However, none of the ethnopharmacological properties has been scientifically evaluated using volatile compounds obtained from its leaves (essential oil). AIM OF THE STUDY: This study investigated the chemical composition, acute oral toxicity, and antinociceptive and anti-inflammatory activities of the essential oil from the leaves of A. cearensis. MATERIAL AND METHODS: The acute toxicity of the essential oil was investigated in mice. The antinociceptive effect was evaluated using the formalin test and, abdominal writhing induced by acetic acid, being investigated the possible mechanisms of action involved in antinociception. The acute anti-inflammatory effect was investigated through models of carrageenan-induced peritonitis, yeast-induced pyrexia, and carrageenan- and histamine-induced paw inflammation. RESULTS: No acute toxicity was observed at doses up to 2000 mg/kg; p.o. The antinociceptive effect was statistically equal to morphine. In the formalin assay, the oil showed analgesic activity in the neurogenic and inflammatory phases, having as mechanisms the cholinergic, adenosinergic system, and ATP-sensitive potassium channels (K-ATP). In peritonitis, a reduction in TNF-α and IL-1ß levels and leukocyte migration were observed. The antipyretic effect was statistically superior to dipyrone. The reduction in paw edema was statistically superior to the standard in both models. CONCLUSION: The results obtained not only support the traditional use of the species in inflammatory conditions and pain in folk medicine but also demonstrate that this is a rich source of phytocomponents such as germacrone, which can be used as a natural and sustainable therapeutic agent with industrial applications.

A Study of the Chemical Composition, Acute and Subacute Toxicity of Bulgarian Tanacetum parthenium Essential Oil.

BACKGROUND: Tanacetum parthenium (L.) Sch.Bip. (T. parthenium) is an aromatic perennial plant belonging to the Asteraceae family, also known as feverfew. It is widely distributed in various regions of Europe and other parts of the world. The plant has a rich background in the traditional medicine of many nations and has been used as a remedy for fever, pain, inflammation, asthma, rheumatism, menstrual disorders, etc. Methods: GC-MS analysis was conducted to determine the chemical composition of the isolated essential oil (EO). Using the method proposed by Litchfield and Wilcoxon, the average lethal dose (LD50) of the EO on Wistar rats was determined for two routes of administration: oral (p.o.) and intraperitoneal (i.p.). The subacute toxicity of the EO was also tested by oral administration of a daily dose of 1.0 g/kg body weight (BW) for 28 days. The toxicity of the EO was evaluated by observing and evaluating changes in behavior, body weight, basic hematological and serum biochemical parameters, and histopathological changes of the internal organs. RESULTS: Thirty-seven volatile organic compounds representing 94.58% of the total oil composition were tentatively detected in the obtained T. parthenium EO. The dominant compounds were camphor (45.47%), trans-chrisantenyl acetate (21.65%), camphene (9.48%), and cis-isogeraniol (5.42%). The results showed that the EO was not toxic when administered in acute oral doses. The acute mean lethal dose for intraperitoneal administration was LD50 i.p. = 2.13 g/kg BW. In the subacute study involving administration of an oral dose of EO for 28 days, there were a number of changes in the hematological and serum biochemical parameters of the blood compared with the control group of animals. However, no symptoms of toxicity, changes in the body weight of the rats, death, or pathological changes in the histological indicators of the examined organs-brain, heart, stomach, liver, spleen and kidney-were found. Extrapolating the results obtained from the rat experiments, we can state that the EO is safe for use in doses below 1 g/kgBW for a period not exceeding one month.

Pharmacokinetic and toxicological prediction of the chemical constituents of the essential oil of the leaves of Croton heliotropiifolius Kunth.

The development of new drugs through studies of candidate molecules is a complex undertaking; however, computational or in silico approaches aimed at optimizing molecules with greater development potential are being utilized for predictions of pharmacokinetic properties such as absorption, distribution, metabolism and excretion (ADME) as well as toxicological parameters. The objective of this study was to examine in silico and in vivo pharmacokinetic and toxicological properties of the chemical constituents present in the essential oil of Croton heliotropiifolius Kunth leaves. The following Pubchem platform as well as Software SwissADME and PreADMET software were employed for in silico studies while micronucleus (MN) testing for in vivo determination of mutagenicity, using Swiss adult male Mus musculus mice. In silico findings demonstrated that all chemical constituents presented (1) high oral absorption (2) medium cellular permeability and (3) high blood brain permeability. As for toxicity, these chemical constituents exhibited low to medium risk of occurrence of cytotoxicity. Regarding in vivo evaluation, peripheral blood samples obtained from animals tested with the oil showed no significant differences in number of MN compared to negative controls. Data indicate that further investigations are necessary to corroborate the findings of this study. Our data suggest that essential oil extracted from Croton heliotropiifolius Kunth leaves may serve as a candidate for new drug development.

Impact of dietary supplementation with Cinnamomum cassia essential oil on silver catfish (Rhamdia quelen): Toxicological effects and muscle antioxidant and fatty acid profiles.

The aim of this study was to determine the biological effects of dietary supplementation with 0.05% and 0.1% cinnamon essential oil extracted from Cinnamomum cassia on silver catfish (Rhamdia quelen). The final body weight, weight gain, and specific growth rate were significantly higher in fish supplemented with 0.05% cinnamon essential oil than in the control(untreated) group. Muscle reactive oxygen species and lipid peroxidation levels were significantly lower in fish supplemented with 0.05% cinnamon essential oil but higher at the 0.1% concentration. Muscle antioxidant capacity against peroxyl radicals (ACAP) and superoxide dismutase activity were significantly higher in fish supplemented with 0.05% cinnamon essential oil, while ACAP levels were lower in fish supplemented with 0.1%. The total saturated fatty acid content was significantly higher in the muscle of supplemented fish than in controls, while the total monounsaturated fatty acid content was significantly higher only in fish fed 0.1% cinnamon essential oil. Finally, the total content of polyunsaturated fatty acids was significantly lower in fish fed 0.1% essential oil. Thus, data demonstrated that 0.05% C. cassia essential oil improves fish health by improving performance and muscle oxidant/antioxidant status. Higher doses of cinnamon essential oil produced oxidative stress in muscle, suggesting toxicity at the 0.1% level. Although this cinnamon essential oil diet exerted positive health effects, this diet impaired the muscle fatty acid profile, suggesting adverse impacts on human health.

Bio-molluscicidal potential and biochemical mechanisms of clove oil and its main component eugenol against the land snail, Theba pisana.

The land snail, Theba pisana is a serious pest that adversely affects various crops in sustainable agriculture. Essential oils and their constituents represent an environmentally sound alternative to synthetic pesticides. Our study aimed to investigate the lethal and sub-lethal toxicity of clove oil and its main component eugenol to understand the mechanisms underlying its toxic action against T. pisana. The GC-MS profile of the clove oil composition was characterized. In the laboratory experiment, LD50 of clove oil and eugenol via the contact testing were determined after 48 and 72 h. Moreover, sub-lethal effects of clove oil or eugenol on the survivors following the exposure of snails to the 25 and 50% of the LD50/48 and 72 h were evaluated through using snail tissues for biochemical measurments. The GC-MS analysis showed that eugenol (64.87%) was the major constituent present in the oil. The results also showed that LD50 values at 48 and 72 h were 2006.5 and 1493.5 µg/g b.w for oil and 239.6 and 195.3 µg/g b.w for eugenol, respectively. Compared to control, the sub-lethal effects of clove oil or eugenol at 48 and 72 h showed a significant increase in reduced glutathione (GSH) levels. Catalase (CAT) and glutathione-S-transferase (GST) activities significantly elevated in oil- or eugenol-treated snails, except at low dose after 48 h. After two exposure times, snails exposed to oil or eugenol at both sub-lethal effects had considerably higher γ-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) activities. Moreover, markedly augmentation in alkaline phosphatase (ALP) and alanine aminotransferase (ALT) activities at all exposure times, with the exception of snails treated with low dose of eugenol after 48 h was observed. Both clove oil and eugenol at the tested doses caused a significant inhibition in acetylcholinesterase (AChE) activity at two exposure times. Our findings highlight the potential of clove oil and eugenol, as an efficient natural molluscicide alternative to its synthetic counterparts for snail control.

Exploration of Synergistic Pesticidal Activities, Control Effects and Toxicology Study of a Monoterpene Essential Oil with Two Natural Alkaloids.

With the increasing development of pest resistances, it is not easy to achieve satisfactory control effects by using only one agrochemical. Additionally, although the alkaloid matrine (MT) isolated from Sophora flavescens is now utilized as a botanical pesticide in China, in fact, its pesticidal activities are much lower in magnitude than those of commercially agrochemicals. To improve its pesticidal activities, here, the joint pesticidal effects of MT with another alkaloid oxymatrine (OMT) (isolated from S. flavescens) and the monoterpene essential oil 1,8-cineole (CN) (isolated from the eucalyptus leaves) were investigated in the laboratory and greenhouse conditions. Moreover, their toxicological properties were also studied. Against Plutella xylostella, when the mass ratio of MT and OMT was 8/2, good larvicidal activity was obtained; against Tetranychus urticae, when the mass ratio of MT and OMT was 3/7, good acaricidal activity was obtained. Especially when MT and OMT were combined with CN, the significant synergistic effects were observed: against P. xylostella, the co-toxicity coefficient (CTC) of MT/OMT (8/2)/CN was 213; against T. urticae, the CTC of MT/OMT (3/7)/CN was 252. Moreover, the activity changes over time of two detoxification enzymes, carboxylesterase (CarE) and glutathione S-transferase (GST) of P. xylostella treated with MT/OMT (8/2)/CN, were observed. In addition, by scanning electron microscope (SEM), the toxicological study suggested that the acaricidal activity of MT/OMT (3/7)/CN may be related to the damage of the cuticle layer crest of T. urticae.

Chemical composition, antinociceptive and anti-inflammatory effects in mice of the essential oil of Psidium cattleyanum Sabine leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: One of the native species of the genus most often mentioned by traditional people is Psidium cattleyanum Sabine, which is used mostly to treat disorders of the respiratory, genitourinary, and digestive systems. These symptoms are mainly treated by the decoction of the leaves. Additionally, there are gaps in the in vivo and toxicity investigations of this species. AIM OF THE STUDY: The aim of this study was evaluate antinociceptive and anti-inflammatory potential of essential oil from P. cattleyanum leaves in vivo. MATERIALS AND METHODS: Gas chromatography-mass spectrometry (GC/MS) was used to examine the essential oil of P. cattleyanum. The acute toxicity test was then done with a 2000 mg/kg dosage. The oil at 50, 100, and 200 mg/kg orally, as well as the reference medications Morphine 10.0 mg/kg IP and/or Indomethacin 20.0 mg/kg IP, were tested using nociception (abdominal writhing, formalin, and tail immersion) and inflammatory models (paw edema and peritonitis). RESULTS: The phytochemical assay showed a high concentration of ß-caryophyllene (46.68%) and α-caryophyllene (10.81%). In the in vivo assays, P. cattleyanum essential oil proved to be an important antinociceptive agent, reaching 76.96% inhibition of abdominal writhing with acetic acid and 67.12% in the formalin assay. An increase in latency time in the tail test was also reported. In the test with carrageenan, the oil showed significant inhibition compared to the control. A decrease in the migration of leukocytes was also reported in the group treated with P. cattleyanum, reaching 60.49% at the dose of 200 mg/kg. CONCLUSIONS: The essential oil from the leaves of P. cattleyanum has anti-inflammatory and antinociceptive action and has potential for application in the pharmaceutical and food industry.

In silico molecular modeling, neuro-behavioral profile, and toxicity assessment of the essential oil of Ferula gummosa Boiss. as an anti-seizure agent.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferula gummosa Boiss., known in Persian as "Baridje," belongs to the Apiaceae family. All parts of this plant, especially the root, contain galbanum. Galbanum, the oleo-gum resin of F. gummosa, is one of the essential traditional herbal medicines in Iran, which is used as a tonic for epilepsy and chorea, memory enhancement, gastrointestinal diseases, and wound healing. AIM OF THE STUDY: We investigated the toxicity, anticonvulsant effects, and molecular modeling of the essential oil (EO) distilled from the oleo-gum resin of F. gummosa. MATERIALS AND METHODS: Gas chromatography-mass spectrometry was used to identify the EO components. The cytotoxicity of EO on HepG2 cell lines was assessed by the MTT method. Male mice were arranged as follows: negative control groups (sunflower oil (10 ml/kg, i.p.) or saline (10 ml/kg, p.o.)), EO groups (0.5, 1, 1.5, and 2.5 ml/kg, p.o.), and positive control groups (ethosuximide (150 mg/kg, p.o.) or diazepam (1.0 or 2 mg/kg, i.p.)). The motor coordination and neurotoxicity of EO were studied using the rota-rod test. Open-field, novel object recognition, and passive avoidance learning tests were used to investigate the effect of EO on locomotor activity and memory function. An acute pentylenetetrazole-induced seizure model was utilized to evaluate the anticonvulsant properties of the EO. The interaction of the EO main components with the GABAA receptor was investigated by coarse-grained molecular dynamics simulations. RESULTS: ß-pinene, sabinene, α-pinene, and ρ-cymene were the main components of EO. The IC50 of the EO at 24, 48, and 72 h was found to be 59.90, 12.96, and 3.93 µl/ml, respectively. No adverse effects were observed in memory, motor coordination, and locomotor activity in mice treated with EO. Administration of EO (1, 1.5, and 2.5 ml/kg) improved survival rates in mice receiving pentylenetetrazole (PTZ; to induce an epileptic seizure). Sabinene was able to bind to the binding site of benzodiazepines at the GABAA receptor. CONCLUSIONS: Acute treatment with the EO of F. gummosa caused antiepileptic effects and could effectively increase the survival rate in PTZ-treated mice with no significant toxicity.

Compositions analysis and insecticidal activity of Aconitum polycarpum Chang ex W.T.Wang petroleum ether fractions and essential oils.

ETHNOPHARMACOLOGICAL RELEVANCE: The Aconitum genus plants as a natural pesticide for insecticide and rodent control has been recorded in Chinese folk. However, the insecticide effect, mechanism, and active composition of Aconitum polycarpum Chang ex W.T.Wang have not been studied further. AIM OF THE STUDY: This study was designed to analyze the chemical composition, evaluate contact toxicity of petroleum ether extracts (PEEs) and essential oils (EOs) of A. polycarpum, and further explore their possible insecticidal mechanism. MATERIALS AND METHODS: The roots of A. polycarpum were extracted with 90% methanol, and then extracted with petroleum ether to obtain PEEs; the EOs was extracted by distillation. The chemical compositions of PEEs and EOs were analyzed by GC-MS. Contact toxicity was evaluated by the immersion method. Exploring insecticidal mechanisms through in vitro enzyme inhibitory activity. RESULTS: 12 compounds were identified from PEEs by GC-MS, mainly including aliphatic (94.8%), the main compositions were Octadecadienol (ODO) (aliphatic, 53.2%) and L-Ascorbyl dipalmitate (LADP) (aliphatic, 36.1%). 24 compounds were identified in EOs. About 44.6% of the identified components were terpenoids and their derivatives, and the rest were mainly aliphatic (34.7%) and phenols (3.0%). The main chemical components were L (-)-Borneol (LB) (terpenoid, 28.3%), LADP (aliphatic, 19.1%), and Isoborneol (terpenoid, 9.1%). The contact toxicity indicated that the PEEs showed great contact toxicity against Spodoptera exigua (LC50 = 126.2 mg/L). Meanwhile, LADP (LC50 = 128.1 mg/L) and ODO (LC50 = 121.3 mg/L) was similar to that of Cyhalothrin (LC50 = 124.2 mg/L) in contact toxicity. In addition, we found that LADP and ODO exhibited excellent inhibitory activity against CarE (IC50 = 58.0, 56.1 mg/L, respectively) by measuring in vitro enzyme inhibitory activity, which was superior than Cyhalothrin (IC50 = 68.1 mg/L). CONCLUSIONS: The chemical compositions and contact toxicity of EOs and PEEs of A. polycarpum were analyzed and evaluated, and their insecticidal mechanisms were preliminarily discussed for the first time. It proved PEEs of A. polycarpum and its main components (LADP and ODO) exhibited excellent contact toxicity against S. exigua, and CarE was identified as a potential target for contact toxicity. This study indicated that the insecticidal activity of petroleum ether extracts from A. polycarpum is quite promising, and provides a practical and scientific basis for the development and application of botanical pesticides.

Eugenia gracillima essential oil has pharmaceutical applications in pain and inflammation without toxic effects in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Eugenia gracillima is widely used by the population in the manufacture of pulps and jellies, with popular reports of its use in the treatment of infections in the urinary system, respiratory and dermatological problems. A previous study reports that EO from E. gracillima leaves proved to be a promising antioxidant agent in combating the promastigote forms of protozoa. Despite this, this species has been little studied due to its pharmacological properties. STUDY OBJECTIVE: In this study, an essential oil extracted (EO) from Eugenia gracillima leaves was evaluated for its acute toxicity and anti-inflammatory, antinociceptive and behavioral effects in mice. METHODS: The EO was obtained by hydrodistillation, and the composition analysis was performed by gas chromatography coupled to mass spectrometry. Acute toxicity assessment was performed with observation of hematological parameters and histopathological evaluation, as well as tests to investigate antinociceptive, anti-inflammatory activities and behavioral effects. RESULTS: Chromatographic analysis showed D-germacrene (16.10%), γ-muurolene-g (15.60%) and bicyclogermacrene (8.53%) as the majority of compounds. In the toxicity evaluation, no death or physiological changes were observed in mice treated with a single oral dose of up to 5000 mg/kg, and it did not lyse erythrocytes in vitro. The hematological parameters evaluated were not changed after treatment; however, 5,000 mg/kg promoted an increase in transaminase levels. In the histopathological evaluation, only the animals that received the dose of 5000 mg/kg showed discrete leukocyte infiltration around the centrilobular vein in the liver. Antinociceptive activity was detected through tests of acetic acid-induced writhing, formalin, and tail flick, promoted in part by the opioid receptor pathway. In the evaluation of anti-inflammatory activity, a reduction in inflammation was observed in the paw edema test and a decrease in the migration of leukocytes and neutrophils in the peritonitis test. The open field and elevated plus maze tests showed that EO did not affect the animals' motor functions or exploratory activity. CONCLUSION: It was concluded that the essential oil of E. gracillima has potential for the development of pharmaceutical formulations with analgesic and anti-inflammatory actions in non-toxic concentrations.

Toxicity and larvicidal activity on Aedes aegypti of citronella essential oil submitted to enzymatic esterification / Toxicidade e atividade larvicida sobre Aedes aegypti de óleo essencial de citronella submetido à esterificação enzimática

Abstract The essential oil of citronella (Cymbopogon winterianus) has several biological activities, among them the insect repellent action. Some studies showed that cinnamic acid esters can be applied as natural pesticides, insecticides and fungicides. In this context, the objective of the present work was to evaluate the production of esters from citronella essential oil with cinnamic acid via enzymatic esterification. Besides, the essential oil toxicity before and after esterification against Artemia salina and larvicidal action on Aedes aegypti was investigated. Esters were produced using cinnamic acid as the acylating agent and citronella essential oil (3:1) in heptane and 15 wt% NS 88011 enzyme as biocatalysts, at 70 °C and 150 rpm. Conversion rates of citronellyl and geranyl cinnamates were 58.7 and 69.0% for NS 88011, respectively. For the toxicity to Artemia salina LC50 results of 5.29 μg mL-1 were obtained for the essential oil and 4.36 μg mL-1 for the esterified oils obtained with NS 88011. In the insecticidal activity against Aedes aegypti larvae, was obtained LC50 of 111.84 μg mL-1 for the essential oil of citronella and 86.30 μg mL-1 for the esterified oils obtained with the enzyme NS 88011, indicating high toxicity of the esters. The results demonstrated that the evaluated samples present potential of application as bioinsecticide.

Resumo O óleo essencial de citronela (Cymbopogon winterianus) possui diversas atividades biológicas, entre elas a ação repelente a insetos. Alguns estudos mostraram que os ésteres do ácido cinâmico podem ser aplicados como pesticidas naturais, inseticidas e fungicidas. Nesse contexto, o objetivo do presente trabalho foi avaliar a produção de ésteres a partir do óleo essencial de citronela com ácido cinâmico via esterificação enzimática. Além disso, foi investigada a toxicidade do óleo essencial antes e após a esterificação contra Artemia salina e a ação larvicida sobre Aedes aegypti. Os ésteres foram produzidos utilizando ácido cinâmico como agente acilante e óleo essencial de citronela (3: 1) em heptano e 15% em peso da enzima NS 88011 como biocatalisadores, a 70 ° C e 150 rpm. As taxas de conversão de cinamatos de citronelil e geranil foram 58,7 e 69,0% para NS 88011, respectivamente. Para a toxicidade sobre Artemia salina foram obtidos CL50 de 5,29 μg mL-1 para o óleo essencial e 4,36 μg mL-1 para os óleos esterificados com NS 88011. Na atividade inseticida contra larvas de Aedes aegypti, obteve-se CL50 de 111,84 μg mL-1 para o óleo essencial de citronela e 86,30 μg mL-1 para os óleos esterificados com a enzima NS 88011, indicando alta toxicidade dos ésteres. Os resultados demonstraram que as amostras avaliadas apresentam potencial de aplicação como bioinseticida.

Toxicity of Essential Oil of Mentha piperita (Lamiaceae) and its Monoterpenoid Menthol Against Tetranychus urticae Kogan 1836 (Acari: Tetranychidae).

Essential oils from plants have remarkable biological properties, for example as insecticides and acaricides. Here we provide chemical analysis and evaluate the toxicity of the essential oil of Mentha piperita (Lamiaceae) and its main constituent menthol against Tetranychus urticae Kogan 1836 (Acari: Tetranychidae), a polyphagous pest present in agricultural landscapes. The essential oil was obtained from M. piperita leaves via hydrodistillation. Subsequently, concentration-response bioassays in adult females (fumigation and contact) were conducted to evaluate the lethal effect on the mite with three exposure intervals. We also evaluated the reproductive performance of females after exposure. Both substances were lethal in the fumigation bioassay, in addition, the essential oil was about 6-fold more toxic than menthol after 24 and 48 h of exposure. The fecundity of T. urticae females decreased inversely proportional to the increase of the used concentrations. Essential oil contact tests showed sublethal effects, with low mortality and reproductive stimulation of T. urticae females. Therefore, menthol and M. piperita essential oil can be considered potential acaricides for T. urticae by fumigant exposure due to the deleterious effect in adults and reduction in the number of individuals in subsequent generations, that represents a promising management tool.

Toxicity of the essential oil from Tetradenia riparia (Hochstetter.) Codd (Lamiaceae) and its principal constituent against malaria and dengue vectors and non-target animals.

Malaria and dengue are diseases transmitted by mosquitoes of the genera Anopheles and Aedes resistant to commercial insecticides, which are toxic to non-target animals. Alternatively, eco-friendly strategies have focused on searching for essential oil (EO) from plants to control these mosquitoes. In this aspect, this study was carried out to investigate the toxicity of the EO from Tetradenia riparia and its main constituent against Anopheles and Aedes larvae and non-target animals Toxorhynchites haemorrhoidalis and Gambusia affinis. The mechanism of the larvicidal action of the EO and its main compound was investigated by the acetylcholinesterase (AChE) inhibition. The EO from T. riparia was extracted by hydrodistillation with yield of 1.4 ± 0.17%. The analysis of the EO by GC-MS and GC-FID revealed fenchone (38.62%) as the main compound. The EO (100 ppm) showed larvicidal activity against Anopheles and Aedes larvae (91 to 100% of mortality) (LC50 from 29.31 to 40.76 ppm). On the other hand, fenchone (10 ppm) showed more activity (89 to 100% of mortality) (LC50 from 5.93 to 7.00 ppm) than the EO. The EO and fenchone caused the inhibition of AChE (IC50 from 1.93 to 2.65 ppm), suggesting the inhibition of this enzyme as a possible mechanism of larvicidal action. Regarding toxicity, the EO (1000 ppm) and fenchone (100 ppm) showed low toxicity against T. haemorrhoidalis and G. affinis (9 to 74% of mortality) (LC50 from 170.50 to 924.89 ppm) (SI/PSF from 17.99 to 31.91) than the α-cypermethrin (0.52 ppm) which was extremally toxic against these non-target animals (100% of mortality, LC50 from 0.22 to 0.29 ppm). This significant larvicidal activity of the T. riparia EO and its main constituent, along with the low toxicity towards non-target organisms indicate these samples as a possible eco-friendly alternative for the control of malaria and dengue vectors.

Effect of thyme essential oil and its two components on toxicity and some physiological parameters in mulberry pyralid Glyphodes pyloalis Walker.

Extensive usage of synthetic pesticides has proved to be destructive to all living being and the resurgence of pest resistance. Compounds derived from certain plants are usually safer compared to chemical control of pest. The present study thus intended to use Thymus vulgaris essential oil (EO) and two of its derivatives including thymol and carvacrol in order to see their deleterious effects on Glyphodes pyloalis (Walker). We also studied the oil components. This pest has recently become a serious concern for the silk industry. Our results showed that the thyme EO contain several components including thymol (26.9%), ρ-Cymene (14.54%), linalool (13.39%) and carvacrol (5.7%). Our toxicity tests revealed an estimated LD50 values for thyme EO, thymol and carvacrol 2.82, 32.18 and 56.54 µg/larva, respectively. However, the thyme EO was more toxic than its two tested compounds. The activity of certain detoxifying enzymes such as α- and ß-esterase, glutathione S-transferase and cytochrome P450 were significantly inhibited by thymol-treated larvae compared to the control group. Similarly, the activity of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and alkaline phosphatases enzymes in thymol-treated larvae decreased while the activity of acid phosphatases increased. Our results suggest that thyme EO and its components have potential for the control of G. pyloalis larvae in mulberry orchards, where no synthetic chemicals are allowed.