Search

Background: Several species of Verbenaceae have been widely used in medicine, and some species of Verbenaceae have been observed good insecticidal activity, such as Lantana camara and Vitex negundo. There is no report about repellent activity of Clerodendrum bungei Steud. (C. bungei) against stored product insects. The chemical composition of C. bungei essential oil (EO) were identified, repellent activity of methanol extract, EO of C. bungei and two main components of EO against T. castaneum, L. serricorne and L. bostrychophila were evaluated for the first time., Results: EO of C. bungei was obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS) and GC. A total of 25 components of the C. bungei EO were identified. The principal compounds in the EO were myristicin (75.0%), 2,2,7,7-Tetramethyltricyclo[6.2.1.0(1,6)]undec-4-en-3-one (4.1%) and linalool (3.4%). Results of bioassays indicated that C. bungei EO exerted strong repellent activity against three target insects. As main constituents, myristicin and linalool also had certain repellency., Conclusion: This work suggests that the EO of C. bungei has promising potential to develop into botanical repellents for the control of pest damage in warehouses and grain stores., (© 2021. Springer Nature Switzerland AG.)

Staphylococcus aureus is a Gram-positive bacterium that is considered an important human pathogen. Due to its virulence and ability to acquire mechanisms of resistance to antibiotics, the clinical severity of S. aureus infection is driven by inflammatory responses to the bacteria. Thus, the present study aimed to investigate the modulating role of citral in inflammation caused by S. aureus infection. For this, we used an isolate obtained from a nasal swab sample of a healthy child attending a day-care centre in Vitória da Conquista, Bahia, Brazil. The role of citral in modulating immunological factors against S. aureus infection was evaluated by isolating and cultivating human peripheral blood mononuclear cells. The monocytes were treated with 4%, 2%, and 1% citral before and after inoculation with S. aureus. The cells were analysed by immunophenotyping of monocyte cell surface molecules (CD54, CD282, CD80, HLA-DR, and CD86) and cytokine dosage (IL-1β, IL-6, IL-10, IL-12p70, IL-23, IFN-γ, TGF-β, and TNF-α), and evaluated for the expression of 84 genes related to innate and adaptive immune system responses. GraphPad Prism software and variables with P values < 0.05, were used for statistical analysis. Our data demonstrated citral's action on the expression of surface markers involved in recognition, presentation, and migration, such as CD14, CD54, and CD80, in global negative regulation of inflammation with inhibitory effects on NF-κB, JNK/p38, and IFN pathways. Consequently, IL-1β, IL-6, IL-12p70, IL-23, IFN-γ, and TNF-α cytokine expression was reduced in groups treated with citral and groups treated with citral at 4%, 2%, and 1% and infected, and levels of anti-inflammatory cytokines such as IL-10 were increased. Furthermore, citral could be used as a supporting anti-inflammatory agent against infections caused by S. aureus. There are no data correlating citral, S. aureus, and the markers analysed here; thus, our study addresses this gap in the literature., (© 2021. The Author(s).)

Natural products, including essential oils and their components, have been used for their bioactivities. Linalool (2,6-dimethyl-2,7-octadien-6-ol) is an aromatic monoterpene alcohol that is widely found in essential oils and is broadly used in perfumes, cosmetics, household cleaners and food additives. This review covers the sources, physicochemical properties, application, synthesis and bioactivities of linalool. The present study focuses on the bioactive properties of linalool, including anticancer, antimicrobial, neuroprotective, anxiolytic, antidepressant, anti-stress, hepatoprotective, renal protective, and lung protective activity and the underlying mechanisms. Besides this, the therapeutic potential of linalool and the prospect of encapsulating linalool are also discussed. Linalool can induce apoptosis of cancer cells via oxidative stress, and at the same time protects normal cells. Linalool exerts antimicrobial effects through disruption of cell membranes. The protective effects of linalool to the liver, kidney and lung are owing to its anti-inflammatory activity. On account of its protective effects and low toxicity, linalool can be used as an adjuvant of anticancer drugs or antibiotics. Therefore, linalool has a great potential to be applied as a natural and safe alternative therapeutic.

This research aims to develop white bread shelf-life extension sachet with controlled release of antimicrobial agent prepared from multicomponent bio-based materials. The structure of antimicrobial sachet consists of two major parts i.e., controlled release part and active part. The first part produced from paper coated with ethylene vinyl alcohol (EVOH). The second one was an active part which produced from biodegradable poly(butylene succinate) (PBS) and geraniol essential oil blend. Inhibition clear zone test results showed that a suitable geraniol concentration, encapsulated in PBS, was 10 wt%. Based on the water vapor transmission test, coating paper with EVOH for three times (around 450 μm) was an optimal condition for the use as a controlled release part. Release test indicated that geraniol migration concentration increased with increasing the relative humidity (RH) in the package which correlated to the moisture liberated from bread slice. Shelf-life extension study informed that the spoilage of bread stored with antimicrobial sachet was delayed by more than three weeks. In summary, this antimicrobial sachet could be used in food shelf-life extension purpose which easily placed in any food container. This is an alternative way of food waste minimization., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Essential oils (EOs) are widely recognized as efficient and safe alternatives for controlling pest insects in foods. However, there is a lack of studies evaluating the toxicological stability of botanical insecticides in stored grains in order to establish criteria of use and ensure your efficiency. The objective of this work was to evaluate the toxicological stability of basil essential oil ( O. basilicum ) and its linalool and estragole components for Sitophilus zeamais (Motschulsky) adults in corn grains by fumigation. The identification of the chemical compounds of the essential oil was performed with a gas chromatograph coupled to a mass selective detector. Mortality of insects was assessed after 24 h exposure. After storage for six (EO) and two months (linalool and estragole) under different conditions of temperature (5, 20, and 35 °C) and light (with and without exposure to light), its toxicological stability was evaluated. Studies revealed that the essential oil of O. basilicum and its main components exhibited insecticidal potential against adults of S. zeamais . For greater toxicological stability, suitable storage conditions for them include absence of light and temperatures equal to or less than 20 °C.

Objectives: Geraniol, a natural monoterpene, is an essential oil component of many plants. Methotrexate is an anti-metabolite drug, used for cancer and autoimmune conditions; however, clinical uses of methotrexate are limited by its concomitant renal injury. This study investigated the efficacy of geraniol to prevent methotrexate-induced acute kidney injury and via scrutinizing the Keap1/Nrf2/HO-1, P38MAPK/NF-κB and Bax/Bcl2/caspase-3 and -9 pathways., Methods: Male Wister rats were allocated into five groups: control, geraniol (orally), methotrexate (IP), methotrexate and geraniol (100 and 200 mg/kg)., Results: Geraniol effectively reduced the serum levels of creatinine, urea and Kim-1 with an increase in the serum level of albumin when compared to the methotrexate-treated group. Geraniol reduced Keap1, escalated Nrf2 and HO-1, enhanced the antioxidant parameters GSH, SOD, CAT and GSHPx and reduced MDA and NO. Geraniol decreased renal P38 MAPK and NF-κB and ameliorated the inflammatory mediators TNF-α, IL-1β, IL-6 and IL-10. Geraniol negatively regulated the apoptotic mediators Bax and caspase-3 and -9 and increased Bcl2. All the biochemical findings were supported by the alleviation of histopathological changes in kidney tissues., Conclusion: The current findings support that co-administration of geraniol with methotrexate may attenuate methotrexate-induced acute kidney injury.

The objective of this study was to evaluate the possible relaxing effect of essential oils (EOs) (Aloysia triphylla and Lippia alba) and phytochemicals (citral and linalool) in the gastropod Pomacea canaliculata. Animals were exposed to compounds at the concentrations range of 25-750 µL L-1. Magnesium chloride (MgCl2, 10-50 g L-1) and control group (ethanol 6.75 mL L-1, highest concentration used for treatment dilution) were also tested. The EOs, citral and MgCl2 had no relaxing effect at the concentrations range tested, and citral caused aversive behavior (closure of the operculum) from 90 μL L-1. Exposure to linalool at 25, 50, 100, 200 and 400 µL L-1 relaxed 28, 76, 88, 96 and 100% of the animals, respectively. The concentrations of 25, 50 and 400 µL L-1 differed statistically from each other, while 100 and 200 µL L-1 were equal to 50 and 400 µL L-1. All animals recovered up to 40 min, except at of 400 µL L-1. Linalool is effective for relaxing P. canaliculata and can be useful in management techniques that require relaxation. However, further studies are needed to certify whether linalool is appropriate for maintaining animal welfare in invasive procedures that require total insensitivity.

Cinnamomum verum is widely used in traditional medicines, and the different parts of the plant, such as bark, leaves, and flowers, are used for essential oil production. The present study compared the chemical composition of the essential oil of C. verum extracted from the leaves and flowers. In addition, efficacy of these essential oils against the two common pests Sitophilus oryzae and Callosobruchus maculatus was also evaluated. The results indicated the presence of cinnamaldehyde, eugenol, caryophyllene, and linalool in these essential oils, however, at different concentrations. The leaf essential oil was found to be 10-20% more effective as a fumigant against both the pests. Likewise, the leaf essential oil found to repel these pests even at lower concentrations than that of flower essential oil of C. verum . Besides, these essential oils were also effective in controlling the growth of various gram positive and gram negative microbial pathogens and possibly a safeguard for human health. On contrary, both the essential oils were found to be safe for the application on grains, as indicated by their germination potentials. It was also observed that these essential oils do not cause any significant toxicity to guppy fishes, thus confirming their ecological safety for use as a biopesticide.

Aeromonas hydrophila is one of the most important aquatic pathogens causing huge economic losses to aquaculture. Linalool, a vital ingredient of a variety of essential oils, was proved as a good antimicrobial agent in our previous studies. However, the low solubility and volatility of Linalool obstruct its application in the field of aquatic drugs. Thus, in this study, Linalool nano-emulsion (LN) was prepared to solve these obstructions. We investigated the physicochemical properties, antibacterial activity, and mode of action of LN against A. hydrophila. LN with different medium chain triglycerides (MCT) concentrations were prepared by ultrasonic method. The results showed that the emulsion droplet size of LN was the smallest when MCT was not added to the formulation. Nano-emulsions are usually less than 500 nm in diameter. In our study, LN in this formulation were spherical droplet with a diameter of 126.57 ± 0.85 nm and showed good stability. LN showed strong antibacterial activity, the MIC and MBC values were 0.3125% v / v and 0.625% v / v , respectively. The bacterial population decreased substantially at 1 × MIC of LN. LN exhibited disruptive effect on cell membranes by scanning electron microscope (SEM) and transmission electron microscope (TEM). The present study provided a formulation of Linalool nano-emulsion preparation. Moreover, the good antibacterial activity of LN showed in our study will promote the application of Linalool for the control and prevention of A. hydrophila in aquaculture.

Background: The transient receptor potential ankyrin 1 (TRPA1) cation channels function as broadly-tuned sensors of noxious chemicals in many species. Recent studies identified four functional TRPA1 isoforms in Drosophila melanogaster (dTRPA1(A) to (D)), but their responses to non-electrophilic chemicals are yet to be fully characterized., Methods: We determined the behavioral responses of adult flies to the mammalian TRPA1 non-electrophilic activators citronellal and menthol, and characterized the effects of these compounds on all four dTRPA1 channel isoforms using intracellular Ca 2+ imaging and whole-cell patch-clamp recordings., Results: Wild type flies avoided citronellal and menthol in an olfactory test and this behavior was reduced in dTrpA1 mutant flies. Both compounds activate all dTRPA1 isoforms in the heterologous expression system HEK293T, with the following sensitivity series: dTRPA1(C) = dTRPA1(D) > dTRPA1(A) ≫ dTRPA1(B) for citronellal and dTRPA1(A) > dTRPA1(D) > dTRPA1(C) > dTRPA1(B) for menthol., Conclusions: dTrpA1 was required for the normal avoidance of Drosophila melanogaster towards citronellal and menthol. All dTRPA1 isoforms are activated by both compounds, but the dTRPA1(B) is consistently the least sensitive. We discuss how these findings may guide further studies on the physiological roles and the structural bases of chemical sensitivity of TRPA1 channels.

The aim of the present study was to encapsulate linalool into chitosan nanocomposite (Nm-linalool) for developing novel controlled release delivery system in order to protect stored rice against fungal infestation, aflatoxin B 1 (AFB 1 ) contamination, and lipid peroxidation. The chitosan-linalool nanocomposite showed spherical shapes, smooth surface with monomodal distribution as revealed by SEM and AFM investigation. FTIR and XRD represented peak shifting and changes in degree of crystallinity after incorporation of linalool into chitosan nanocomposite. Nanoencapsulation of linalool showed higher zeta potential and lowered polydispersity index. TGA analysis reflected the stability of Nm-linalool with reduced weight loss at varying temperatures. Biphasic pattern, with initial rapid release followed by sustained release illustrated controlled delivery of linalool from chitosan nanocomposite, a prerequisite for shelf-life enhancement of stored food products. Chitosan nanocomposite incorporating linalool displayed prominent antifungal and antiaflatoxigenic activity during in vitro as well as in situ investigation in rice with improved antioxidant potentiality. Further, Nm-linalool displayed considerable reduction of lipid peroxidation in rice without exerting any adverse impact on organoleptic attributes. In conclusion, the investigation strengthens the application of chitosan-linalool nanocomposite as an innovative controlled nano-delivery system for its practical application as novel environmentally friendly eco-smart preservative in food and agricultural industries., (Copyright © 2021 Elsevier B.V. All rights reserved.)

For combating life-threatening infections caused by Candida albicans there is an urgent requirement of new antifungal agents with a targeted activity and low host cytotoxicity. Manipulating the mechanistic basis of cell death decision in yeast may provide an alternative approach for future antifungal therapeutics. Herein, the effect of an active citral derivative (Cd1) over the physiology of cell death in C. albicans was assessed. The viability of C. albicans SC5314 cells was determined by broth microdilution assay. The crucial morphological changes and apoptotic markers in Cd1-exposed yeast cells were analyzed. Subsequently the results confirmed that Cd1 arrested growth and caused death in yeast cells. Furthermore, this molecule inhibited antioxidant enzymes that resulted in production of reactive oxygen species. DNA fragmentation and condensation, phosphatidylserine exposure at the outer leaflet of cell membrane, mitochondrial disintegration as well as accumulation of cells at G2/M phase of the cell cycle were recorded. Altogether, this derivative induced apoptotic-type cell death in C. albicans SC5314., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: Zinc oxide nanoparticles (ZnO-NPs) are currently applied in food and pharmaceutical industries whose neurotoxic effect on the central nervous system (CNS) is a major concern. Considering the pharmacological properties (antioxidant, anti-inflammatory) of the geraniol (GE), we aimed to investigate the efficacy of geraniol on ZnO-NPs neurotoxicity., Materials and Methods: We used 32 male Wistar rats, randomly assigned to four groups (n = 8): Control, GE (daily received 100 mg/kg of GE by gavage), ZnO-NPs (received intraperitoneal injection of 75 mg/kg of ZnO-NPs twice a week), and ZnO-NPs + GE (received both GE and ZnO-NPs at same doses above during 4 weeks). Morris water maze (MWM) and Y-maze tasks were done to evaluate learning and memory function. Biochemical assays were done to measure total antioxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX) and ZnO-NPs bioaccumulation. Nissl and H&E staining were performed for histological evaluations., Key Findings: The results of behavioral study revealed that GE improved learning and memory impairment induced by ZnO-NPs. Moreover, neuroprotective effect of GE significantly decreased pathological parameters such as necrosis and gliosis, and consequently increased the number of nerve cells in the cortex and different hippocampal areas. Furthermore, biochemical studies demonstrated that GE significantly increased antioxidant indices (namely, TAC, SOD, and GPX) and reduced oxidative stress marker (MDA) and Zn bioaccumulation in ZnO-NPs treated animals., Significance: Our results provide experimental evidence to further investigate the precise mechanisms underlying the geraniol as a promising therapeutic approach for improvement of cognitive function and neurotoxicity induce by ZnO-NPs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Essential oils' active compounds present great potential as a bactericidal agent in active packaging. The encapsulation in polymeric walls promotes their protection against external agents besides allowing controlled release. This work produced PLA capsules with three different active compounds, Cinnamomum cassia essential oil (CEO), eugenol (EEO), and linalool (LEO), by emulsion solvent evaporation method. Characterizations included SEM, Zeta potential, FTIR, TGA, and bactericidal activity against E. coli, S. aureus, L. monocytogenes, and Salmonella. The active compounds showed microbiological activity against all pathogens. CEO capsules showed superior colloidal stability. The active compounds' presence in all capsules was confirmed by FTIR analysis, with possible physical interaction between CEO, EEO, and the polymeric matrix, while LEO had a possible chemical interaction with PLA. TGA analysis showed a plasticizing effect of active compounds, and the loading efficiency was 39.7%, 50.7%, and 22.3% for CEO-PLA, EEO-PLA, and LEO-PLA, respectively. The capsules presented two release stages, sustaining activity against pathogens for up to 28 days, indicating a satisfactory internal morphology. This study presented methodology for encapsulation of antimicrobial compounds that can be suitable for active food packaging. CEO-PLA capsules regarding stability and antibacterial activity achieved the best results., (Published by Elsevier B.V.)

Background: Aspergillus ochraceus causes food spoilage and produces mycotoxin ochratoxin A (OTA) during storage of agricultural commodities. In this study, citral was used to inhibit A. ochraceus growth and OTA accumulation, proteomic analysis was employed to verify the mechanism of citral., Results: Citral was found to significantly inhibit fungal growth and mycotoxin production in A. ochraceus. Specifically, 75, 125, 150 and 200 μL L -1 citral suppressed mycelial growth by 33%, 46%, 50% and 100%, respectively. Additionally, 75 μL L -1 citral inhibited OTA accumulation by 25%. Proteomic analysis was performed to elucidate the inhibitory mechanism of citral on mycelial growth and OTA production at subinhibitory concentrations (75 μL L -1 ). Proteomics analysis identified 2646 proteins in A. ochraceus fc-1, of which 218 were differentially expressed between control and 75 μL L -1 citral treatment samples. Differentially expressed proteins were identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of biological process, cellular component and molecular function terms. Potential factors affecting mycelial growth and OTA production were analysed, and OTA production was revealed to be a complex process involving many associated factors related to various processes including nutrient intake, sterol biosynthesis, ribosome biogenesis, energy metabolism, oxidative stress and amino acid metabolism. In addition, citral at 75 μL L -1 down-regulated OTA biosynthetic genes including pks and nrps, but slightly up-regulated the global regulatory factors veA, velB and laeA., Conclusion: The findings further demonstrate the potential of citral for the preservation of grains and other agricultural products, and provide new insight into its antifungal mechanisms at subinhibitory concentrations. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Lindera umbellata ( Lu ) essential oil primarily contains linalool and has relaxation properties. We investigated the psychological and antibacterial effects of footbath with Lu essential oil. The participants included 20 women without medical history and received two intervention plans: footbath without any essential oil and footbath using Lu essential oil. Next, questionnaires regarding impressions and mood states were provided for them to answer. In addition, their autonomic nervous system activity was measured, and the aerobic viable of count on the feet was determined. The high-frequency value reflecting the parasympathetic nervous system activity significantly increased after footbath using Lu essential oil. In the questionnaire about the mood states, the subscale scores of tension-anxiety, depression, fatigue, and confusion after intervention were lower than those before intervention regardless of the use of the essential oil. Conversely, the anger-hostility score decreased only in the group using Lu essential oil. Furthermore, the decrease in aerobic viable count after intervention was not significantly different between the two groups. Footbath using Lu essential oil increased the parasympathetic nervous system activity and relieved anger. Taken together, we suggest that footbath using Lu essential oil has a relaxation effect.

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for high morbidity and mortality rates. Citral has been studied in the pharmaceutical industry and has shown antimicrobial activity. This study aimed to analyze the antimicrobial activity of citral in inhibiting biofilm formation and modulating virulence genes, with the ultimate goal of finding a strategy for treating infections caused by MRSA strains. Citral showed antimicrobial activity against MRSA isolates with minimum inhibitory concentration (MIC) values between 5 mg/mL (0.5%) and 40 mg/mL (4%), and minimum bactericidal concentration (MBC) values between 10 mg/mL (1%) and 40 mg/mL (4%). The sub-inhibitory dose was 2.5 mg/mL (0.25%). Citral, in an antibiogram, modulated synergistically, antagonistically, or indifferent to the different antibiotics tested. Prior to evaluating the antibiofilm effects of citral, we classified the bacteria according to their biofilm production capacity. Citral showed greater efficacy in the initial stage, and there was a significant reduction in biofilm formation compared to the mature biofilm. qPCR was used to assess the modulation of virulence factor genes, and icaA underexpression was observed in isolates 20 and 48. For icaD, seg, and sei, an increase was observed in the expression of ATCC 33,591. No significant differences were found for eta and etb. Citral could be used as a supplement to conventional antibiotics for MRSA infections., (© 2021. The Author(s).)

Nerol, a monoterpene is evident to possess diverse biological activities, including antioxidant, anti-microbial, anti-spasmodic, anthelmintic, and anti-arrhythmias. This study aims to evaluate its hepatoprotective effect against paracetamol-induced liver toxicity in a rat model. Five groups of rats (n = 7) were orally treated (once daily) with 0.05% tween 80 dissolved in 0.9% NaCl solution (vehicle), paracetamol 640 mg/kg (negative control), 50 mg/kg silymarin (positive control), or nerol (50 and 100 mg/kg) for 14 days, followed by the hepatotoxicity induction using paracetamol (PCM). The blood samples and livers of the animals were collected and subjected to biochemical and microscopical analysis. The histological findings suggest that paracetamol caused lymphocyte infiltration and marked necrosis, whereas maintenance of the normal hepatic structural was observed in group pre-treated with silymarin and nerol. The rats pre-treated with nerol significantly and dose-dependently reduced the hepatotoxic markers in animals. Nerol at 100 mg/kg significantly reversed the paracetamol-induced altered situations, including the liver enzymes, plasma proteins, antioxidant enzymes and serum bilirubin, lipid peroxidation (LPO) and cholesterol [e.g., total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c)] levels in animals. Taken together, nerol exerted significant hepatoprotective activity in rats in a dose-dependent manner. PCM-induced toxicity and nerol induced hepatoprotective effects based on expression of inflammatory and apoptosis factors will be future line of work for establishing the precise mechanism of action of nerol in Wistar albino rats., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Geraniol, a natural compound found in the essential oils of various aromatic plants, has attracted attention for its probable anticancer effects. The molecular mechanisms of the cell proliferation suppression and apoptosis induction via geraniol in gastric cancer cells (AGS), however, remain unclear. Gastric cancer cells were treated with geraniol, and it was found that the IC 50 values were 25 μM/ml, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Results showed that 20 and 25 μM geraniol-induced reactive oxygen species (ROS) production (2'-7'dichlorofluorescin diacetate staining) and decreased mitochondrial membrane potential (rhodamine 123 staining) in AGS cells. Then, it effectively inhibited cell growth and induced apoptosis, confirmed through acridine orange/ethidium bromide, 4',6-diamidino-2-phenylindole, and propidium iodide staining and molecular marker analysis in AGS cells. Also, geraniol potently diminished caspase-9, Bax, Bcl-2, and caspase-3 expression in AGS cells. We also evaluated the essential mechanism of the cytotoxic effect of geraniol. Moreover, the present study depicted that geraniol-induced cell death through mitochondrial ROS production and inhibited the phosphorylation form of mitogen-activated protein kinase (p38, MAPK, JNK, and ERK1/2) signaling pathway. Taken together, these results concluded that geraniol has a novel therapeutic property against human stomach cancer., (© 2021 Wiley Periodicals LLC.)

Angiogenesis crucially contributes to various diseases, such as cancer and diabetic retinopathy. Hence, anti-angiogenic therapy is considered as a powerful strategy against these diseases. Previous studies reported that the acyclic monoterpene linalool exhibits anticancer, anti-inflammatory and anti-oxidative activity. However, the effects of linalool on angiogenesis still remain elusive. Therefore, we investigated the action of (3R)-(-)-linalool, a main enantiomer of linalool, on the angiogenic activity of human dermal microvascular endothelial cells (HDMECs) by a panel of angiogenesis assays. Non-cytotoxic doses of linalool significantly inhibited HDMEC proliferation, migration, tube formation and spheroid sprouting. Linalool also suppressed the vascular sprouting from rat aortic rings. In addition, Matrigel plugs containing linalool exhibited a significantly reduced microvessel density 7 days after implantation into BALB/c mice. Mechanistic analyses revealed that linalool promotes the phosphorylation of extracellular signal-regulated kinase (ERK), downregulates the intracellular level of adenosine triphosphate (ATP) and activates the transient receptor potential cation channel subfamily M (melastatin) member (TRPM)8 in HDMECs. Inhibition of ERK signaling, supplementation of ATP and blockade of TRPM8 significantly counteracted linalool-suppressed HDMEC spheroid sprouting. Moreover, ATP supplementation completely reversed linalool-induced ERK phosphorylation. In addition, linalool-induced ERK phosphorylation inhibited the expression of bone morphogenetic protein (BMP)-2 and linalool-induced TRPM8 activation caused the inhibition of β1 integrin/focal adhesion kinase (FAK) signaling. These findings indicate an anti-angiogenic effect of linalool, which is mediated by downregulating intracellular ATP levels and activating TRPM8., (© 2021. The Author(s).)

Ethnopharmacological Relevance: Cymbopogon citratus (DC.) Stapf (C. citratus) is consumed as an infusion in folk medicine due to its pharmacological properties and action in the central nervous system. Epilepsy is a neurological disorder that affects millions of people. Since the currently available antiepileptic drugs often cause undesirable side effects, new alternative therapeutic strategies based on medicinal plants have been proposed., Aim of the Study: This study aimed to investigate the anticonvulsant and neuroprotective effects of C. citratus essential oil (EO) and hydroalcoholic extract (E1) from its leaves, as well as of its related compounds citral (CIT) and geraniol (GER) against the effects of pentylenetetrazole (PTZ) induced seizures in zebrafish (Danio rerio)., Materials and Methods: To evaluate the anticonvulsant properties of the samples, adult animals were pre-treated (by immersion) and subsequently exposed to PTZ solution. The involvement of GABA A receptors in the antiepileptic effects was investigated by the coadministration of flumazenil (FMZ), a known GABA A receptor antagonist. Oxidative stress markers malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and nitric oxide (NO) were assessed in zebrafish brain homogenates after PTZ exposure., Results: All samples increased the latency time for the first seizure, which was reduced when animals were pretreated with FMZ, suggesting the involvement of GABA A receptors in the observed properties. The association between CIT and GER at the lowest concentration studied showed a synergistic effect on the anticonvulsant activity. Decreases in MDA and NO levels and increases in GSH and CAT levels in the brain of treated animals suggested the neuroprotective effect of the compounds investigated., Conclusions: Our results proved that C. citratus EO, E1, CIT and GER have anticonvulsant effects in zebrafish and could be used as a promising adjuvant therapeutic strategy for epilepsy treatment. Furthermore, zebrafish demonstrated to be an alternative animal model of epilepsy to evaluate the anticonvulsant and neuroprotective effects of C. citratus., (Copyright © 2021. Published by Elsevier B.V.)

Trichophyton rubrum causes ringworm worldwide. Citral (CIT), extracted from Pectis plants, is a monoterpene and naturally composed of geometric isomers neral ( cis -citral) and geranial ( trans -citral). CIT has promising antifungal activities and ergosterol biosynthesis inhibition effects against several pathogenic fungi. However, no study has focused on neral and geranial against T. rubrum , which hinders the clinical application of CIT. This study aimed to compare antifungal activities of neral and geranial and preliminarily elucidate their ergosterol biosynthesis inhibition mechanism against T. rubrum . Herein, the disc diffusion assays, cellular leakage measurement, flow cytometry, SEM/TEM observation, sterol quantification, and sterol pattern change analyses were employed. The results showed geranial exhibited larger inhibition zones ( p < 0.01 or 0.05), higher cellular leakage rates ( p < 0.01), increased conidia with damaged membranes ( p < 0.01) within 24 h, more distinct shriveled mycelium in SEM, prominent cellular material leakage, membrane damage, and morphological changes in TEM. Furthermore, geranial possessed more promising ergosterol biosynthesis inhibition effects than neral, and both induced the synthesis of 7-Dehydrodesmosterol and Cholesta-5,7,22,24-tetraen-3β-ol, which represented marker sterols when ERG6 was affected. These results suggest geranial is more potent than neral against T. rubrum , and both inhibit ergosterol biosynthesis by affecting ERG6.

Geraniol, an acyclic monoterpene present in several plant species' essential oils, is utilized as a food additive. It possesses potent antiproliferative and antitumor effects ascribed to its antiinflammatory, and antioxidant properties. The study aimed to understand geraniol's mechanism in human lung and skin cancer cells by employing molecular and cell target-based assays. SRB, NRU, MTT assays, qRT-PCR, molecular docking, and EAC model were used. Geraniol inhibits the proliferation of PC-3, A431, and A549 cells (~50%) and suppresses the activity of ornithine decarboxylase (15.42 ± 0.61 μM) and hyaluronidase (57.61 ± 8.53 μM) in A549 cells; LOX-5 (25.44 ± 3.50 μM) and hyaluronidase (90.71 ± 2.38 μM) in A431 cells. The qRT-expression analysis of the targeted gene depicts non-significant change at the transcriptional level of LOX-5 in A431 cells. A robust binding interaction of geraniol with molecular targets was observed in the molecular docking studies. In Ehrlich Ascites Carcinoma model, geraniol inhibit tumor growth by 50.08% at 75 mg/kg bw and was found to be safe up to 1,000 mg/kg bw in a toxicity study. Geraniol has two prenyl units allied head-to-tail and functionalized with one hydroxyl group at its tail end could be responsible for the antiproliferative activity. These observations provide evidence for geraniol to be used as a new prototype to develop a novel anticancer agent., (© 2021 John Wiley & Sons Ltd.)

In order to improve the anti-inflammatory activity of chitosan oligosaccharide (COS), chitosan oligosaccharide graft citronellol derivatives (COS-g-Cit1-3) were successfully synthesized via grafting citronellol (Cit) onto COS backbone. The degrees of substitution (DS) of COS-g-Cit1-3 were 0.165, 0.199 and 0.182, respectively. The structure of COS-g-Cit1-3 was confirmed by UV-vis, FT-IR, 1 H NMR and elemental analysis. The in vivo anti-inflammatory activity evaluation results displayed that COS-g-Cit1-3 drastically reduced the paw swelling, and the oedema inhibitions were 22.58 %, 29.03 % and 25.81 %, respectively. The results indicated that the anti-inflammatory effects of COS-g-Cit1-3 were significantly higher than COS and COS-g-Cit2 exhibited the highest anti-inflammatory ability. The results also presented that COS-g-Cit1-3 reduced the expression levels of TNF-α by promoting the secretion of IL-4 and IL-10. Moreover, western blot analysis data proved that COS-g-Cit1-3 inactivated the NF-κB signaling pathway via inhibiting the phosphorylation of p65, IKBα and IKKβ., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Fresh herbs are not commonly associated with foodborne pathogens, due to the production of essential oils with antimicrobial activity. Recalls of contaminated basil, and basil outbreaks caused by Salmonella motivated studies aimed to comprehend the antimicrobial activity of basil essential oils, and to explore the mechanisms in which Salmonella can overcome them. Linalool, a major constituent of basil oil, increases the permeability of Salmonella Senftenberg cells by damaging their membrane. Linalool also induces bacterial aggregation. We hypothesized that the membrane perforation effect triggers cell aggregation through leakage of intracellular substances from live and dead cells. By exposing S. Senftenberg to additional physical (sonication) or chemical (eugenol, Triton-X-100) treatments, we showed that the aggregation is caused by various membrane-targeted treatments. Enzymatic degradation of leaked proteins restricted the bacterial aggregation, and disassembled existing aggregates. Moreover, supplemented proteins such as bacterial intracellular proteins or BSA also caused aggregation, further supporting the hypothesis that non-specific proteins trigger the bacterial aggregation. This study provides a novel understanding of the role of protein leakage in promoting bacterial aggregation. Since aggregation has significant roles in food safety and microbial ecology, this finding may establish future studies about microbial resistance via formation of clusters similar to biofilm development., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Food packaging films were coated with polyvinyl acetate (PVA) containing different concentrations of citral or Litsea (L.) cubeba essential oil (EO). Antimicrobial contact trials in style of ISO22916 were performed. Citral coatings achieved bactericidal effects against Escherichia coli (2.1 log) and Staphylococcus aureus (4.3 log) at concentrations of 20% DM . L. cubeba inactivated more than 4 log cycles of both bacteria at a concentration of 20% DM . To determine the antimicrobial activity across the gas phase, a unique method for volatile agents was developed, adapting ISO22196. GC/MS measurements were performed to supplement microbiological tests in a model packaging system with a defined 220 ml headspace (HS). HS-equilibrium concentrations of 1.8 μg/ml Air were found for 20% DM ' citral-coatings, resulting in antimicrobial effects of 3.8 log against of E. coli. Saccharomyces cerevisiae (4.74 log) and Aspergillus niger (4.29 log) were more effectively inactivated by 3% DM and 5% DM coatings. In an application trial with strawberries, simulating a headspace packaging, growth inhibitory effects on the yeast and mold microbiota were found for the 20% DM coatings., (Copyright © 2020. Published by Elsevier Ltd.)

Cinnamomum plants (Lauraceae) are a woody species native to South and Southeast Asia forests, and are widely used as food flavors and traditional medicines. This study aims to evaluate the chemical constituents of Cinnamomum osmophloeum ct. linalool leaf oil, and its antidepressant and motor coordination activities and the other behavioral evaluations in a rodent animal model. The major component of leaf oil is linalool, confirmed by GC-MS analysis. Leaf oil would not induce the extra body weight gain compared to the control mice at the examined doses after 6 weeks of oral administration. The present results provide the first evidence for motor coordination and antidepressant effects present in leaf oil. According to hypnotic, locomotor behavioral, and motor coordination evaluations, leaf oil would not cause side effects, including weight gain, drowsiness and a diminishment in the motor functions, at the examined doses. In summary, these results revealed C. osmophloeum ct. linalool leaf essential oil is of high potential as a therapeutic supplement for minor/medium depressive syndromes.

With an upsurge in multidrug resistant bacteria backed by biofilm defence armours, there is a desperate need of new antibiotics with a non-traditional mechanism of action. Targeting bacteria by misguiding them or halting their communication is a new approach that could offer a new way to combat the multidrug resistance problem. Quorum sensing is considered to be the achilles heel of bacteria that has a lot to offer. Since, both quorum sensing and biofilm formation have been related to drug resistance and pathogenicity, in this study we synthesised new derivatives of citral with antiquorum sensing and biofilm disrupting properties. We previously reported antimicrobial and antiquorum sensing activity of citral and herein we report the synthesis and evaluation of citral and its derivatives (CD1-CD3) for antibacterial, antibiofilm and antiquorum sensing potential against Chromobacterium violaceum using standard methods. Preliminary results revealed that CD1 is the most active of all the derivatives. Qualitative and quantitative evaluation of antiquorum sensing activity at sub-inhibitory concentrations of these compounds also revealed high activity for CD1 followed by CD2, CD3 and citral. These compounds also inhibit biofilm formation at subinhibitory concentrations without causing any bacterial growth inhibition. These results were replicated by RT-qPCR with down regulation of the quorum sensing genes when C. violaceum was treated with these test compounds. Overall, the results are quite encouraging, revealing that biofilm and quorum sensing are interrelated processes and also indicating the potential of these derivatives to impede bacterial communication and biofilm formation.

The oil from the leaves of Limnocitrus littoralis (Miq.) Swingle was obtained by hydrodistillation and investigated by gas chromatography combined with mass spectrometry (GC/MS), the anti-inflammatory effect of the oil was examined on a LPS-induced RAW264.7 cells. An aggregate of forty components were identified, representing 93.0% of the oil. This oil was subjugated by monoterpene hydrocarbons (27.7%), sesquiterpene hydrocarbons (32.3%) and oxygenated sesquiterpenes (4.6%). The significant constituents of L. littoralis essential oil were determined as follows; myrcene (24.9%), γ-muurolene (11.0%), and oleic acid (10.3%). The essential oil of L. littoralis showed activity against the nitric oxide (NO) generation with the IC 50 value to 12.50 ± 1.19 µg/L. The anti-inflammatory effect of essential oil from the leaves of L. littoralis is reported for the first time.

Linalool odor exposure induces an analgesic effect in mice. This effect disappeared in the anosmic model mice, indicating that olfactory input evoked by linalool odor triggered this effect. Furthermore, hypothalamic orexinergic neurons play a pivotal role in this effect. However, the neuronal circuit mechanisms underlying this effect have not been fully addressed. In this study, we focused on the descending orexinergic projection to the spinal cord and examined whether this pathway contributes to the effect. We assessed the effect of intrathecal administration of orexin receptor antagonists on linalool odor-induced analgesia in the tail capsaicin test. We found that the selective orexin type 1 receptor antagonist, but not the selective orexin type 2 receptor antagonist, prevented the odor-induced analgesic effect. Furthermore, immunohistochemical analyses of c-Fos expression induced by the capsaicin test revealed that neuronal activity of spinal cord neurons was suppressed by linalool odor exposure, which was prevented by intrathecal administration of the orexin 1 receptor antagonist. These results indicate that linalool odor exposure drives the orexinergic descending pathway and suppresses nociceptive information flow at the spinal level.

We compared the ability of product formulations representing a synthetic pyrethroid acaricide (Talstar P Professional Insecticide), a natural product-based acaricide (Essentria IC3), and an entomopathogenic fungal acaricide (Met52 EC Bioinsecticide) to suppress Ixodes scapularis Say and Amblyomma americanum (L.) nymphs when applied following USEPA approved manufacturers' label recommendations for tick control using hand-pumped knapsack sprayers before the beginning of their seasonal activity period in the spring. We applied Met52 EC Bioinsecticide (11% Metarhizium anisopliae Strain F52) to five 100 m2 plots (10.6 ml AI/plot) in mid-April 2020. Two weeks later at the end of April 2020, we treated an additional five 100 m2 plots each with either Talstar P Professional Insecticide (7.9% bifenthrin @ 2.5 ml AI/plot) or Essentria IC3 (10% rosemary oil, 5% geraniol, and 2% peppermint oil @ 86.6 ml AI/plot). Weekly sampling of all plots through the end of June 2020 showed that both Met52 EC Bioinsecticide and Essentria IC3 failed to maintain a 90% suppression threshold for I. scapularis, compared to control plots, and required two additional applications over the course of the trial. In contrast, Talstar P Professional Insecticide suppressed 100% of I. scapularis nymphs and ≥96 and 100% of A. americanum nymphs and adults, respectively. Such pre-season applications of synthetic pyrethroids significantly reduce the early season acarological risk for exposure to host-seeking ticks as well as the frequency of acaricide applications., (© The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Terpenes are vital metabolites found in various plants and animals and known to be beneficial in the treatment of various diseases. Previously, our group identified terpenes that increased the survival of Alzheimer's disease (AD) model flies expressing human amyloid β (A β ) and identified linalool as a neuroprotective terpene against A β toxicity. Linalool is a monoterpene that is commonly present as a constituent in essential oils from aromatic plants and is known to have anti-inflammatory, anticancer, antihyperlipidemia, antibacterial, and neuroprotective properties. Although several studies have shown the beneficial effect of linalool in AD animal models, the mechanisms underlying the beneficial effect of linalool on AD are yet to be elucidated. In the present study, we showed that linalool intake increased the survival of the AD model flies during development in a dose-dependent manner, while the survival of wild-type flies was not affected even at high linalool concentrations. Linalool also decreases A β -induced apoptosis in eye discs as well as the larval brain. Moreover, linalool intake was found to reduce neurodegeneration in the brain of adult AD model flies. However, linalool did not affect the total amount of A β 42 protein or A β 42 aggregation. Rather, linalool decreased A β -induced ROS levels, oxidative stress, and inflammatory response in the brains of AD model flies. Furthermore, linalool attenuated the induction of oxidative stress and gliosis by A β 1-42 treatment in the rat hippocampus. Taken together, our data suggest that linalool exerts its beneficial effects on AD by reducing A β 42-induced oxidative stress and inflammatory reactions., Competing Interests: The authors declare that they have no potential conflicts of interest, including any financial, personal, or other relationships, with other people or organizations., (Copyright © 2021 Chunyu Yuan et al.)

Rhabdomyosarcoma (RMS) is a rare type of soft tissue sarcoma most commonly found in pediatric patients. Despite progress, new and improved drug regimens are needed to increase survival rates. Citral, a natural product plant oil can induce cell death in cancer cells. Another compound, metformin, isolated originally from French lilac and used by diabetics, has been shown to reduce the incidence of cancer in these patients. Application of citral to RMS cells showed increase in cell death, and RD and RH30 cells showed half maximal inhibitory concentration (IC 50 ) values as low as 36.28 μM and 62.37 μM, respectively. It was also shown that the citral initiated cell apoptosis through an increase in reactive oxygen species (ROS) and free calcium. In comparison, metformin only showed moderate cell death in RMS cell lines at a very high concentration (1,000 μM). Combinatorial experiments, however, indicated that citral and metformin worked antagonistically when used together. In particular, the ability of metformin to quench the ROS induced by citral could lead to the suppression of activity. These results clearly indicate that while clinical use of citral is a promising anti-tumor therapy, caution should be exercised in patients using metformin for diabetes., (© 2020 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.)

Essential oils and their main components, monoterpenes, have been proven to be important alternatives for the control of pathogenic and spoiling microorganisms, but the mode of action of these compounds is poorly understood. This work aimed to determine the mode of action of citral and geraniol on the model yeast Saccharomyces cerevisiae using a flow cytometry approach. Exponentially growing yeast cells were treated with different concentrations of citral and geraniol for 3 h, and evaluated for cell wall susceptibility to glucanase, membrane integrity, reactive oxygen species (ROS) accumulation, mitochondrial membrane potential, and metacaspase activity. Results provide strong evidence that citral and geraniol acute fungicidal activity against Saccharomyces cells involves the loss of membrane and cell wall integrity resulting in a dose-dependent apoptotic/necrotic cell death. However, yeast cells that escape this first cell membrane disruption, particularly evident on sub-lethal concentration, die by metacaspase-mediated apoptosis induced by the accumulation of intracellular ROS. The deleted mutant on the yca1 gene showed high tolerance to citral and geraniol.

Doxorubicin (DOX) is a very effective broad-spectrum anticancer drug, yet its clinical application is badly restricted due to its serious side effects. Citronellal (CT), a specialized metabolite of plants found in Cymbopogon spp., is proved to exhibit many beneficial properties. In the current study, we intended to investigate the effect of CT on DOX-induced hepatotoxicity in rats. Rats were treated with CT (200 mg/kg b.w./day orally), and given DOX (2.5 mg/kg b.w./week, intraperitoneally) to induce hepatotoxicity for six consecutive weeks. The results showed that CT administration could attenuate the DOX-induced pathological changes of liver tissues and ameliorated the inappropriate alteration of liver function biomarkers (serum glutamic aspartate aminotransferase, glutamic pyruvic transaminase, and albumin) in serum and oxidative stress parameters (malondialdehyde, superoxide dismutase, and reduced glutathione) in the liver. Moreover, CT mitigated the Bax/Bcl-2 ratio and caspase-3 expression to inhibit cell apoptosis. Further study indicated that CT therapy could enhance the protein levels of p-PI3K, p-Akt, and CD31 in the liver. These results demonstrate that CT can ameliorate DOX-induced hepatotoxicity in rats mediated by antioxidative stress, antiapoptosis, and proangiogenesis., (© 2020 The Authors. Journal of Biochemical and Molecular Toxicology Published by Wiley Periodicals LLC.)

The demand for reduced chemical preservative usage is currently growing, and natural preservatives are being developed to protect seafood. With its excellent antibacterial properties, linalool has been utilized widely in industries. However, its antibacterial mechanisms remain poorly studied. Here, untargeted metabolomics was applied to explore the mechanism of Shewanella putrefaciens cells treated with linalool. Results showed that linalool exhibited remarkable antibacterial activity against S. putrefaciens , with 1.5 µL/mL minimum inhibitory concentration (MIC). The growth of S. putrefaciens was suppressed completely at 1/2 MIC and 1 MIC levels. Linalool treatment reduced the membrane potential (MP); caused the leakage of alkaline phosphatase (AKP); and released the DNA, RNA, and proteins of S. putrefaciens , thus destroying the cell structure and expelling the cytoplasmic content. A total of 170 differential metabolites (DMs) were screened using metabolomics analysis, among which 81 species were upregulated and 89 species were downregulated after linalool treatment. These DMs are closely related to the tricarboxylic acid (TCA) cycle, glycolysis, amino acid metabolism, pantothenate and CoA biosynthesis, aminoacyl-tRNA biosynthesis, and glycerophospholipid metabolism. In addition, linalool substantially affected the activity of key enzymes, such as succinate dehydrogenase (SDH), pyruvate kinase (PK), ATPase, and respiratory chain dehydrogenase. The results provided some insights into the antibacterial mechanism of linalool against S. putrefaciens and are important for the development and application of linalool in seafood preservation.

Alzheimer's disease (AD) is a neurodegenerative disorder leading to cognitive deficits and cognitive decline. Since no cure or preventing therapy is currently available to counteract AD, natural-derived compounds are investigated to find new potential neuroprotective agents for its treatment. In the present study, we tested the neuroprotective effect of lavender and coriander essential oils (EOs) and their main active constituent linalool, against the neurotoxicity elicited by Aβ 1-42 oligomers, a key molecular factor in the neurodegeneration of AD. Importantly, our findings on neuronally differentiated PC12 cells exposed to Aβ 1-42 oligomers are in accordance with previous in vivo studies reporting the neuroprotective potential of lavender and coriander EOs and linalool. We found that lavender and coriander EOs at the concentration of 10 μg/mL as well as linalool at the same concentration were able to improve viability and to reduce nuclear morphological abnormalities in cells treated with Aβ 1-42 oligomers for 24 hours. Lavender and coriander EOs and linalool also showed to counteract the increase of intracellular reactive oxygen species production and the activation of the pro-apoptotic enzyme caspase-3 induced by Aβ 1-42 oligomers. Our findings provide further evidence that these EOs and their main constituent linalool could be natural agents of therapeutic interest against Aβ 1-42 -induced neurotoxicity., (© 2020 John Wiley & Sons Ltd.)

Background: Triple-Negative Breast Cancer (TNBC) requires targeted therapies to better manage and prevent metastatic mammary gland tumors. Due to the resistance problem associated with the approved drugs, researchers are now focusing on phytochemicals for the treatment of TNBC as they possess pleiotropic mode of action and fewer side effects., Objective: To investigate the antiproliferative effect of citronellal on triple-negative breast cancer cells., Methods: Anticancer potential of citronellal was explored by employing SRB, MTT, and NRU antiproliferative assay. Further, the effect of citronellal was observed on molecular targets (Tubulin, COX-2, and LOX-5) utilizing in vitro and in silico methods. Furthermore, the efficacy of citronellal was examined on Ehrlich Ascites Carcinoma cells. In addition, the safety profiling of it was observed at 300 and 1000 mg/kg of body weight in mice., Results: Citronellal suppresses the growth of MDA-MB-231 cells by more than 50% in NRU assay and ~41% and 32% in SRB and MTT assay, respectively. Further, citronellal's effect was observed on molecular targets wherein it suppressed LOX-5 activity (IC50 40.63±2.27 μM) and prevented polymerization of microtubule (IC50 63.62 μM). The result was more prominent against LOX-5 as supported by molecular docking interaction studies, but a non-significant effect was observed at the transcriptional level. The efficacy of citronellal was also determined in Ehrlich Ascites Carcinoma (EAC) model, wherein it inhibited the growth of tumor cells (45.97%) at 75 mg/kg of body weight. It was non-toxic up to 1000 mg/kg of body weight in mice and did not cause significant lysis of erythrocytes., Conclusion: These observations could provide experimental support for citronellal to be used as a chemopreventive agent for breast cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Linalool, a major odorous constituent in essential oils extracted from lavender, is known to have a wide range of physiological effects on humans including pain management. The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) is involved in transmission of orofacial nociceptive responses through thin myelinated A[Formula: see text] and unmyelinated C primary afferent fibers. Up to date, the orofacial antinociceptive mechanism of linalool concerning SG neurons of the Vc has not been completely clarified yet. To fill this knowledge gap, whole-cell patch-clamp technique was used in this study to examine how linalool acted on SG neurons of the Vc in mice. Under a high chloride pipette solution, non-desensitizing and repeatable linalool-induced inward currents were preserved in the presence of tetrodotoxin (a voltage-gated Na[Formula: see text]channel blocker), CNQX (a non-NMDA glutamate receptor antagonist), and DL-AP5 (an NMDA receptor antagonist). However, linalool-induced inward currents were partially suppressed by picrotoxin (a GABA[Formula: see text] receptor antagonist) or strychnine (a glycine receptor antagonist). These responses were almost blocked in the presence of picrotoxin and strychnine. It was also found that linalool exhibited potentiation with GABA- and glycine-induced responses. Taken together, these data show that linalool has GABA- and glycine-mimetic effects, suggesting that it can be a promising target molecule for orofacial pain management by activating inhibitory neurotransmission in the SG area of the Vc.

Background: Citral is one of the main components of lemongrass oil present at a concentration of 65-85% approximately and is generally separated by steam refining. It is an important component in the manufacturing of scents, citrus chemicals, cosmetics, food and pharmaceutical products., Objectives: This article aims at reviewing the published literature to highlight the metabolism, extraction strategies and therapeutic significance of citral for improving the scope of its application in the food and pharma industry., Discussions: Apart from steam refining, there are other techniques like solvent extraction, supercritical fluid extraction and ultrasonication by which citral can be extracted and the method of extraction defines its quality. It is an unstable molecule and undergoes rapid deterioration on exposure to air. Citral is biosynthesized by the plants through the 5 carbon precursor isopentenyl diphosphate (IPP) units utilizing two diverse biochemical pathways, acetate- mevalonate (acetate- MVA) pathway or 2C-methylerythritol-4-phosphate (MEP). Orally Citral was absolutely digested in the gastrointestinal tract and its metabolism leads to the discharge of metabolites which include a number of acids and a biliary glucuronide. There is no scientific evidence about the long term bioavailability of citral in the body and it has no adverse effect on tissue related to its accumulation and delayed excretion. Citral exhibits various important therapeutic properties like antimicrobial, antioxidant, anticancer, anti-diabetic and anti-inflammatory., Conclusion: Citral is a potent biomolecule with various important biological activities and therapeutic implications. Strategies are required to increase the stability of citral which could increase its applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A new chitosan oligosaccharide derivative (COS-N-Ger), based on geraniol (Ger) modificated onto the NH 2 position of chitosan oligosaccharide (COS) via a facile method, was prepared and employed to evaluate in vitro antibacterial activity. The structures of COS-N-Ger derivatives were confirmed by FT-IR, 1 H, 13 C NMR, and elemental analysis. The characterization results showed successful synthesis of derivatives and the degrees of substitution (DS) of COS-N-Ger1-3 were from 0.260 to 0.283 with the yields up to 78 %. The in vitro antibacterial activity evaluation results presented a significant inhibition effect of COS-N-Ger1-3 derivatives on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as compared to COS. Moreover, their antibacterial activities were dose-dependent and more sensitive to S. aureus than E. coli. The results provide reliable theoretical supports for exploring the application of COS derivatives in the food industry as new potential antibacterial agents., (Copyright © 2020. Published by Elsevier Ltd.)

The extensive use of chemical pesticides in agricultural production has caused great damage to the soil and ecological environment. Citral, a monoterpene aldehyde, has been shown to inhibit the growth of a variety of pathogenic fungi by affecting mitochondrial structure. However, the high volatility and chemical instability of citral may restrict its applications in the agricultural industries. In this study, a concise and facile method for the preparation of modified copolymer chitosan/carboxymethyl cellulose (CS/CMC) hydrogels microspheres loaded with citral was developed to increase and stabilize the bioavailability of this natural bioactive substance. Polyelectrolyte composite scaffold hydrogel microspheres were synthesized by polycationic chitosan (CS) and polyanionic carboxymethyl (CMC). Citral was embedded into the microspheres by coupling the carbonyl group of citral with the amino group of CS to form a Schiff base structure. The effects of three parameters including CS/CMC weight ratio, concentration of CMC and citral on the loading ratio were investigated and optimal loading of 68% was achieved based on single-factor experiments. X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM) were employed to confirm and characterize the structure and surface morphology of the microspheres. Both the XRD and FTIR spectra indicated that the microspheres contain -C=N- covalent bonds between CS and citral. The hydrogel microspheres with incorporated citral exhibited effective and improved in vitro antibacterial effects against E. coli, S. aureus and B. subtilis than non-loaded CS microspheres. Moreover, CS/CMC-citral-MPs showed a good antifungal effect in vivo in reducing disease incidence caused by the plant pathogenic fungus Botrytis cinerea in Solanum lycopersicum. Different from the previous applications of CS and citral in the preservation of picked fruits, citral was embedded into CS/CMC microspheres to achieve improved plant protection against Botrytis cinerea. The microspheres are a promising green antimicrobial agent against plant pathogens in crop protection and other fields., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Deregulated activity of protein kinase B/mammalian target of rapamycin complex-1 (Akt/mTORC1) incites crucial pathological characteristics of diabetic nephropathy. The acyclic monoterpene geraniol has been recently reported to possess antidiabetic effects; however, its potential renoprotective effect in diabetes has not yet been elucidated. This study aimed to assess the possible modulatory effect of geraniol on the Akt/mTORC1 pathway in diabetes-induced nephropathy in rats compared to the standard antidiabetic drug gliclazide. Geraniol and gliclazide was administered daily to diabetic rats for 6 weeks starting on the 3rd-day post diabetes induction by streptozotocin (STZ). Geraniol amended the deteriorated renal function (serum creatinine; blood urea nitrogen). It exerted a remarkable antihyperglycemic effect that is comparable to that of gliclazide and suppressed the fibrotic marker, transforming growth factor-β. Geraniol restored redox balance and inhibited lipid peroxidation by reducing nicotine amide adenine dinucleotide phosphate oxidase and enhancing the antioxidant enzyme, superoxide dismutase. These beneficial effects were associated with a robust downregulation of miRNA-21 and consequently, reversion of tumor suppressor protein phosphatase and tension homolog (PTEN)/Akt/mTORC1 cue and its downstream proteins required for mesangial cell proliferation and matrix protein synthesis. The current study indicates that geraniol interfered with miRNA-21/ PTEN/AKT/mTORC1 pathway signaling that contributes largely to the progression of mesangial expansion and extracellular matrix deposition in diabetic nephropathy.

The aim of this study was to evaluate a hurdle strategy for orange-tangerine (OT) and orange-banana-mango-kiwi-strawberry (OBMKS) juices processing based on UV-C treatment assisted or not by mild heat and the addition of natural antimicrobials. Vanillin and citral emulsions were successfully encapsulated using maltodextrin and HI-CAP (5,18,3) and characterized. The susceptibility of Lactobacillus plantarum ATCC 8014, Escherichia coli ATCC 25922, and Saccharomyces cerevisiae KE 162 to binary mixtures of the encapsulated agents was examined in culture media according to the Berenbaum experimental design. The boundary between growth and non-growth as a function of vanillin and citral concentrations was predicted by means of the probabilistic model using logistic regression. Microbial inactivation achieved by pilot-scale UV-C light (0-390 mJ/cm 2 ) on its own, assisted by mild heat (50 °C, UV-C/H) and combined with antimicrobials (1000 ppm vanillin plus 100 ppm citral) addition (UV-C + A/UV-C/H + A) was assessed in OT and OBMKS. Yeast induced damage in a model solution treated by UV-C + A was studied by flow cytometry (FC). All the antimicrobial mixtures resulted in additive effects (FIC index = 1), thus offering through the probabilistic models a range of formulation possibilities with antimicrobial capacity encompassing lower vanillin and citral concentrations compared to those required when used alone (V range  = 0-1875 ppm plus C range  = 392-0 ppm). UV-C led up to 3.7-3.8, 2.4-3.6 and 1.5-1.6 log-reductions of E. coli, L. plantarum and S. cerevisiae in OT and OBMKS, respectively. A significant increase of 1.7-2.2, 2.1-2.7 and 4.1-5.3 log cycles in microbial inactivation was observed after UV-C/H treatment. Additional inactivation of 0.7-3.1 and 0.5-2.7 log reductions were observed for E. coli and S. cerevisiae, respectively, when UV-C + A and UV-C/H + A were applied in both juices. Therefore, the addition of antimicrobials to the UV-C treated juices, showed additive to synergistic effects on E. coli and S. cerevisiae, respectively along refrigerated storage. A shift from yeast cells with intact membrane and esterase activity in control samples to cells with permeabilized membrane in C + A, UV-C and UV-C + A samples were determined by FC. The shift was more noticeable in UV-C + A samples. Sublethally damaged cells were only detected in C + A and UV-C samples. This study demonstrates that combining a pilot-scale UV-C treatment with the addition of chosen binary mixtures of vanillin and citral, can ensure more than 5 log-reductions of E. coli, L. plantarum and S. cerevisiae in OT and OBKMS juice blends., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Anopheles gambiae s.s. is a key vector of Plasmodium parasites. Repellents, which may be a promising alternative to pesticides used to control malaria mosquitoes. Although citronellal is a known mosquito repellent, its repellency characteristics are largely unknown. Determining the specific odorant-binding proteins (OBPs) and odorant receptors (ORs) that detect and transfer the citronellal molecule in A. gambiae s.s. will help to define the mode of action of this compound. In this research, we assessed the repellent activity of citronellal in A. gambiae s.s. using a Y-tube olfactory meter, screened candidate citronellal-binding OBPs and ORs using reverse molecular docking, clarified the binding properties of predicted proteins for citronellal using fluorescence competition binding assay. Results showed that citronellal had a dosage effect on repelling A. gambiae s.s.. The 50% repellent rate was determined to be 4.02 nmol. Results of simulated molecular docking showed that the only proteins that bound tightly with citronellal were AgamOBP4 and AgamORC7. Fluorescence competitive binding assays confirmed the simulations. This research determined that citronellal was captured by AgamOBP4 and transmitted to AgamORC7 in A. gambiae s.s.. Our study will be beneficial in the further understanding the repellent mechanism of citronellal against A. gambiae s.s..

Background: Epithelial ovarian cancer (EOC) is a fatal gynecologic malignancy that is usually treated with chemotherapy after surgery. However, patients who receive chemotherapy experience severe side effects because of the inherent toxicity and high dose of chemotherapeutics. To overcome these issues, we suggest a combination therapeutic strategy using liposomes encapsulating linalool nanoemulsions (LN-NEs) and doxorubicin (DOX), a chemotherapeutic drug, to increase their synergistic antitumor efficacy and reduce the incidence of side effects from chemotherapeutics for EOC., Methods: The physical properties of LN-NE-DOX-liposomes were characterized by light scattering with a particle size analyzer. Cell viability was determined by MTT assay. Therapeutic efficacy was evaluated in a mouse HeyA8 EOC tumor model of ovarian carcinoma. Additionally, biochemical toxicity was analyzed for levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and blood urea nitrogen (BUN) using BALB/c nude mice., Results: The size of the liposomes encapsulating LN-NEs and DOX (LN-NE-DOX-liposomes) was 267.0 ± 4.6 nm, with a loading efficiency of 55.1 ± 3.1% and 27.2 ± 0.9% for linalool and DOX, respectively. Cell viability after treatment with LN-NE-DOX-liposomes was significantly decreased compared to that of cells treated with DOX liposomes, and apoptosis was significantly increased. Additionally, LN-NE-DOX-liposomes significantly inhibited HeyA8 EOC tumor growth compared to that of the control ( p < 0.01) and DOX-liposome-treated groups ( p < 0.05), while decreasing cell proliferation (Ki67) and microvessel density (CD31), and promoting apoptosis (caspase-3) compared to the control ( p < 0.05). Moreover, the liposomal formulations induced no significant differences in biochemical toxicity (AST, ALT, and BUN) compared to healthy control mice, indicating that the liposomal formulations showed no overt toxicity in mice., Conclusion: This study demonstrates that the production of LN-NE-DOX-liposomes is a pivotal approach for EOC treatment, suggesting a novel combination therapeutic strategy., Competing Interests: The authors declare that they have no competing financial or non-financial interests., (© 2020 Wi et al.)

Background: The monoterpene linalool is a well-known essential oil component produced by several aromatic plants. Cisplatin is a widely used anticancer drug that produces many side effects, particularly nephrotoxicity. Here, we aimed to inspect linalool's protective activity against cisplatin-induced nephrotoxicity and explore part of the underlying mechanisms., Methods: Male Wistar rats were given linalool (50 and 100 mg/kg/day orally) for 15 days; then challenged with cisplatin (8 mg/kg) on the 12th day. Renal function parameters, oxidative stress, inflammatory and apoptotic markers, and toll-like receptor pathway gene, and protein expressions were investigated. Histopathology, immunohistochemistry, and cell-line mediated cytotoxicity assays were conducted., Results: Linalool ameliorated kidney function after cisplatin challenge and managed all oxidation system parameters including GSH, SOD, CAT, MDA, NADPH, and particularly the Nrf2-mediated pathway markers. Linalool decreased TLR4, MYD88 and TRIF gene and protein expressions; diminished related inflammatory mediators such as TNF-α, IL-1β, IL-6, and NF-κB; and down-regulated HMBG1. Linalool mitigated cisplatin-induced apoptotic markers such as caspase 3, caspase 9, and Bax expression, and boosted the anti-apoptotic Bcl2 expression. Linalool potentiated the cytotoxic effect of cisplatin when investigated on HeLa and PC3 human cancer cell lines., Conclusion: Linalool could protect against cisplatin-induced kidney function and tissue damage.

Ethno-Pharmacological Relevance: Lavender oil (LO) is an aromatic/essential oil extracted from Lavandula angustifolia and traditionally used as an aromatherapy massage oil due to its anti-inflammatory and wound healing property and also for providing the relief in other skin conditions such as psoriasis, dermatitis and eczema. However, LO has not been evaluated scientifically for psoriasis like skin inflammation., Aim of the Study: This study was aimed to investigate the LO and its major components linalool (L) and linalyl acetate (LA) against psoriasis like skin inflammation., Materials and Methods: Anti-psoriatic activity was done using Imiquimod (IMQ) induced psoriasis like skin inflammation in BALB/c mice. Assessment of anti-psoriatic effect of LO, L and LA was done on the basis of change in ear thickness, psoriasis area severity index (PASI) scoring at alternative day, CosCam scoring using skin analyzer equipped with SkinSys software, biochemical, immunohistochemical and histological investigations. Level of effectiveness against psoriasis was investigated by percent reduction in PASI scores, CosCam scores and level of Th-1 and Th-17 cell expressing cytokines, as compared to the diseased mice., Results: Topical application of LO 10% showed 73.67% recovery in PASI and 87% in Th-17 cell-specific cytokines towards normal as compared to disease group. L and LA were identified as the major components of LO and favoured ligands for selected psoriasis targets. At 2% topical dose, L and LA showed 64% and 47.61% recovery in PASI scores, respectively. Both, L and LA showed significant recovery in Th-1 specific TNF-α and IL-1β however, only L showed significant recovery of Th-17 cytokines (IL-17 and IL-22). In contrast to LA (which restored granulosis), L restored epidermal hyperplasia and parakeratosis toward the normal condition. On the other hand, L also reduced the expression of NF-κβ, ccr6 and IL-17, while LA reduced the expression of NF-κβ only. At 10% topical dose, LO was observed to be slight irritant while at 2% topical dose, L and LA were found non-irritant to the skin., Conclusion: This study proves the effectiveness of LO and its major phytoconstituents linalool and linalyl acetate against IMQ induced psoriasis like skin inflammation and provides the scientific evidence for topical use of lavender oil., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Citral is a mixture of monoterpenes present in the essential oil of several plants, such as Cymbopogon citratus and Zingiber officinale , possessing anti-inflammatory, anti-ulcerogenic, and antipyretic actions. We investigated the action of citral on body temperature (Tb) and inflammatory signaling in eutrophic and obese mice during Systemic Inflammation (SI) induced by Lipopolysaccharide (LPS). Thus, we assessed the effect of citral (25, 100, and 300 mg/kg) and ibuprofen in LPS-induced SI in Swiss male mice fed a standard diet (SD) or high-fat diet (HFD) for 12 weeks. Following SI induction, we measured Tb and collected the serum, hypothalamus, and gastric mucosa for biochemical measurements. Acute treatment with citral decreased the Tb of both SD and HFD-fed animals. Citral (300 mg/kg) treatment caused a significantly lower Tb variation in HFD-fed animals than in those fed the SD. Citral reduced peripheral levels of tumor necrosis factor (TNF)-α in SD and HFD mice and decreased serum leptin concentration in HFD mice 90 min after the LPS challenge. Furthermore, citral also reduced interleukin (IL)-6 levels in the hypothalamus of obese mice. In summary, citral effectively reduced Tb during SI by reducing inflammatory mediators with a distinct action profile in HFD mice when compared with SD.