Citral

Glycerosome of Melissa officinalis L. Essential Oil for Effective Anti-HSV Type 1.[Pubmed:32650414]

Molecules. 2020 Jul 8;25(14). pii: molecules25143111.

Essential oils are complex mixtures of strongly active compounds, very volatile and sensitive to light, oxygen, moisture and temperature. Loading inside nanocarriers can be a strategy to increase their stability and successfully use them in therapy. In the present study, a commercial Melissa officinalis L. (Lamiaceae) essential oil (MEO) was analyzed by gas chromatography-mass spectrometry, loaded inside glycerosomes (MEO-GS) and evaluated for its anti-herpetic activity against HSV type 1. MEO-GS analyses were prepared by the thin layer evaporation method and they were characterized by light scattering techniques, determining average diameter, polydispersity index and zeta-potential. By transmission electron microscopy, MEO-GS appeared as small nano-sized vesicles with a spherical shape. MEO encapsulation efficiency inside glycerosomes, in terms of Citral and beta-caryophyllene, was found to be ca. 63% and 76% respectively, and MEO release from glycerosomes, performed by dialysis bag method, resulted in less than 10% within 24h. In addition, MEO-GS had high chemical and physical stability during 4 months of storage. Finally, MEO-GS were very active in inhibiting HSV type 1 infection of mammalian cells in vitro, without producing cytotoxic effects. Thus, MEO-GS could be a promising tool in order to provide a suitable anti-herpetic formulation.

Cymbopogon flexuosus essential oil as an additive improves growth, biochemical and physiological responses and survival against Aeromonas hydrophila infection in Nile tilapia.[Pubmed:32638863]

An Acad Bras Cienc. 2020;92 Suppl 1:e20190140.

The objective of the present study was to evaluate growth, biochemical, hematological and intestinal enzymes responses and survival of Nile tilapia juveniles fed a diet containing the essential oil of lemongrass Cymbopogum flexuosus (EOCF) and infected by Aeromonas hydrophila. Five diets were evaluated (in quadruplicate) with increasing levels of EOCF (0.0 - control; 0.25; 0.50; 1.0 and 2.0 mL kg diet-1). On day 45, eight fish per treatment were sampled and blood, liver and intestine samples were taken. Others eight fish per treatment were infected with A. hydrophila followed by a 15-day period of observation. Citral is the main constituent of EOCF. The inclusion of 2.0 mL EOCF kg diet-1 increased specific growth rate and survival after A. hydrophila infection and decreased feed conversion ratio of Nile tilapia. In general, higher concentrations of EOCF in the diet reduced plasma glucose and triglycerides levels, and increased plasma amino acids, alanine aminotransferase (ALT) and hepatic ALT levels, hematological parameters, and the activity of intestinal enzymes. It was concluded that the inclusion of 2.0 mL EOCF kg diet-1 improved growth performance, biochemical and physiological responses and decreased mortality of Nile tilapia after A. hydrophila infection.

Citryl-imine-PEG-ylated chitosan hydrogels - Promising materials for drug delivery applications.[Pubmed:32599243]

Int J Biol Macromol. 2020 Jun 26. pii: S0141-8130(20)33674-6.

The present paper focuses on the synthesis and characterization of new hydrogels and drug delivery systems, designed for local therapy. The hydrogels were obtained by reacting PEG-ylated chitosan derivatives with Citral in different molar ratios of their functionalities. The drug delivery systems were obtained by the in situ hydrogelation of PEG-ylated chitosan derivatives with Citral, in the presence of a hydrophilic anti-inflammatory drug, diclofenac sodium salt. The hydrogels and the drug delivery systems were characterized from the structural, supramolecular and morphological points of view by FTIR spectroscopy, wide angle X-ray diffraction, polarized optical microscopy and scanning electron microscopy. The in vitro release kinetics of the drug has been monitored in physiological conditions, while the in vivo release was evaluated by the somatic pain model on rats. The in vitro enzymatic degradability of the hydrogels was evaluated in the presence of lysozyme, leading to a significant mass loss of 47% in 21days. All the findings, recommend the investigated materials as promising candidates for local drug delivery applications.

Chemosensory reception in the stingless bee Tetragonisca angustula.[Pubmed:32593653]

J Insect Physiol. 2020 Jun 26;125:104076.

In stingless bees, unlike honey bees, the relationship between chemosensory abilities and colony labor division has been poorly studied. Here we examined odor reception and gustatory responsiveness of the stingless bee Tetragonisca angustula focusing on workers, whose are involved in different tasks. Using the proboscis extension response, we studied sucrose response thresholds (SRTs) of foragers and guards. Peripheral responses to odors at the antennae were recorded by electroantennography (EAG). Additionally, we quantified and described the number and type of sensilla present on the antennae using scanning electron microscopy. Foragers' SRTs changed according to the resource collected: nonpollen foragers showed higher SRTs than pollen foragers and guards, that showed similar sucrose responsiveness. EAG signal strength of both foragers and guards increased with increasing odor concentration. Interestingly, guard bees showed the highest response to Citral, an odor that triggers defensive behavior in T. angustula. Type and number of sensilla present in the antennae of guards and foragers were similar. Our results suggest that differences found in chemosensory responses among worker subcastes are task dependent.

Acute Toxicity and Sublethal Effects of Lemongrass Essential Oil and Their Components against the Granary Weevil, Sitophilus granarius.[Pubmed:32570794]

Insects. 2020 Jun 18;11(6). pii: insects11060379.

In the present work, we evaluate the toxic and repellent properties of lemongrass (Cymbopogon citratus (DC. ex Nees) Stapf.) essential oil and its components against Sitophilus granarius Linnaeus as an alternative to insecticide use. The lethal dose (LD50 and LD90), survivorship, respiration rate, and repellency on adults of S. granarius exposed to different doses of lemongrass oil and some of its components were evaluated. The chemical composition of the essential oil was found to have the major components of neral (24.6%), Citral (18.7%), geranyl acetate (12.4%), geranial (12.3%), and limonene (7.55%). Lemongrass essential oil (LD50 = 4.03 microg.insect(-1)), Citral (LD50 = 6.92 microg.insect(-1)), and geranyl acetate (LD50 = 3.93 microg.insect(-1)) were toxic to S. granarius adults. Survivorship was 99.9% in insects not exposed to lemongrass essential oil, decreasing to 57.6%, 43.1%, and 25.9% in insects exposed to LD50 of essential oil, Citral, and geranyl acetate, respectively. The insects had low respiratory rates and locomotion after exposure to the essential oil, geranyl acetate, and Citral. Our data show that lemongrass essential oils and their components have insecticidal and repellent activity against S. granarius and, therefore, have the potential for application in stored grain pest management schemes.

Antitumor and Anti-Metastatic Effects of Citral-Loaded Nanostructured Lipid Carrier in 4T1-Induced Breast Cancer Mouse Model.[Pubmed:32526880]

Molecules. 2020 Jun 9;25(11). pii: molecules25112670.

Cancer nano-therapy has been progressing rapidly with the introduction of many novel drug delivery systems. The previous study has reported on the in vitro cytotoxicity of Citral-loaded nanostructured lipid carrier (NLC-Citral) on MDA-MB-231 cells and some preliminary in vivo antitumor effects on 4T1 breast cancer cells challenged mice. However, the in vivo apoptosis induction and anti-metastatic effects of NLC-Citral have yet to be reported. In this study, the in vitro cytotoxic, anti-migration, and anti-invasion effects of NLC-Citral were tested on 4T1 breast cancer cells. In addition, the in vivo antitumor effects of oral delivery of NLC-Citral was also evaluated on BALB/c mice induced with 4T1 cells. In vitro cytotoxicity results showed that NLC-Citral and Citral gave similar IC50 values on 4T1 cells. However, wound healing, migration, and invasion assays reflected better in vitro anti-metastasis potential for NLC-Citral than Citral alone. Results from the in vivo study indicated that both NLC-Citral and Citral have anti-tumor and anti-metastasis effects, whereby the NLC-Citral showed better efficacy than Citral in all experiments. Also, the delay of tumor progression was through the suppression of the c-myc gene expression and induction of apoptosis in the tumor. In addition, the inhibition of metastasis of 4T1 cells to lung and bone marrow by the NLC-Citral and Citral treatments was correlated with the downregulation of metastasis-related genes expression including MMP-9, ICAM, iNOS, and NF-kB and the angiogenesis-related proteins including G-CSF alpha, Eotaxin, bFGF, VEGF, IL-1alpha, and M-CSF in the tumor. Moreover, NLC-Citral showed greater downregulation of MMP-9, iNOS, ICAM, Eotaxin, bFGF, VEGF, and M-CSF than Citral treatment in the 4T1-challenged mice, which may contribute to the better anti-metastatic effect of the encapsulated Citral. This study suggests that NLC is a potential and effective delivery system for Citral to target triple-negative breast cancer.

Effect of allelochemicals on photosynthetic and antioxidant defense system of Ulva prolifera.[Pubmed:32504860]

Aquat Toxicol. 2020 Jul;224:105513.

Ulva prolifera is a macroalgae that forms massive blooms, negatively impacting natural communities, aquaculture operations and recreation. The effects of the natural products, eugenol, beta-myrcene, Citral and nonanoic acid on the growth rate, antioxidative defense system and photosynthesis of Ulva prolifera were investigated as a possible control strategy for this harmful taxon. Negative effects on growth were observed with all four chemicals, due to the excessive production of reactive oxygen species and oxidative damage to the thalli. However, the response of U. prolifera under the four chemicals stress was different at the cellular level. beta-myrcene, the most effective compound in terms of growth inhibition, induced oxidative stress as shown by the damage of total antioxidant capacity (T-AOC) and the downregulation of the glutathione-ascorbate (GSH-ASA) cycle which inhibited the antioxidative system. This chemical also inhibited photosynthesis and photoprotection mechanisms in U. prolifera, resulting in growth limitation. In contrast, U. prolifera was less affected by the second tested chemical, eugenol, and showed no significant change on photosynthetic efficiency in the presence of the chemical. The inhibition effects of the third and fourth tested chemicals, nonanoic acid and Citralon, on growth and on the antioxidant defense system in U. prolifera were inferior. These results provide a potential avenue for controlling green tides in the future.

The protective effect of Sophora japonica on prostatic hypertrophy and inflammation in rat.[Pubmed:32504221]

Inflammopharmacology. 2020 Jun 5. pii: 10.1007/s10787-020-00723-5.

The atypical adenomatous hyperplasia (AAH) is invariably an incidental histological change, with no clinical findings specific for its diagnosis, and the mean patient age at diagnosis is 64-70 years. The incidence of AAH varies between 1.5 and 19.6% of transurethral resections and in up to 33% of radical prostatectomies. Herbal medicines are becoming a popular option in the treatment of prostatic-related diseases, such as date palm pollen and saw palmetto in the treatment of prostatic hyperplasia. A testosterone/Citral-induced AAH in Wistar rat model was used to evaluate the protective effect of Sophora japonica fruit extract (SFE). The present study suggests that SFE has an ameliorating effect on the prostatic hypertrophy and inflammation through its effect on clusterin, IGF, IL-6, IL-8, TNF-alpha, and TGF-beta1 expression. In addition, the administration of SFE ameliorated the inflammatory score, and histopathological changes in AAH-induced rats in a dose-dependent manner. The treatment with SFE reduced the number of prostatic acini in AAH rat model and decreased the production of pro-inflammatory cytokines. The fruit extract of S. japonica was characterized by determination total phenol content (60.3 mg of gallic acid equivalent/g of dry extract), total flavonoid content (97.9 mg quercetin equivalent/g of dry extract) and the major isoflavonoid sophoricoside (302.9 +/- 2.6 microg/g of the extract). In conclusion, SFE has an ameliorating effect on the prostatic hypertrophy and inflammation. This effect may be attributed to the ability of SFE to decrease the production of pro-inflammatory cytokines, TNF-alpha, IL-1beta and IGF-1 as well as an increase in TGF-beta1.

Anxiolytic properties of Cymbopogon citratus (DC.) stapf extract, essential oil and its constituents in zebrafish (Danio rerio).[Pubmed:32473367]

J Ethnopharmacol. 2020 May 28;260:113036.

ETHNOPHARMACOLOGICAL RELEVANCE: Cymbopogon citratus (DC.) Stapf (Poaceae) leaves is often consumed as infusion in folk medicine due to its therapeutic properties. This plant is also rich in essential oil, which has several beneficial effects to the human health. It is known that medications commonly used to treat anxiety disorders cause undesirable side effects. Thus, it is important to evaluate the anxiolytic effects of natural products from plants, such as C. citratus, as an alternative therapy to treat these disorders. OBJECTIVE: The aim of this study was to investigate the anxiolytic properties of C. citratus essential oil (EO), hydroalcoholic extract (E1), Citral (CIT), geraniol (GER) and the mixture of these terpenoids, as well as its possible mechanism of action by using zebrafish as an anxiety model. METHODS: Adult zebrafish were treated (by immersion) with C. citratus EO, E1, CIT and/or GER. The anxiolytic effects were analyzed by using the light-dark test. The mechanism involved in the anxiolytic effects was further investigated by the coadministration of flumazenil (FMZ), an antagonist of GABAA receptors. The total polyphenols (phenolic and flavonoid compounds) content of E1 was determined by using spectrophotometric assays. RESULTS: All analyzed samples showed a remarkable anxiolytic effect on zebrafish in the highest concentrations, as the animals showed a preference for the light side of the tank. Furthermore, the observed effect of EO, E1, CIT and GER was reversed by pre-treatment with FMZ, suggesting that GABAergic receptors were involved in the anxiolytic effect displayed by these samples. The association between CIT and GER in the lowest studied concentrations showed an interesting synergistic behavior on anxiolytic effect observed in light-dark test. Besides, it was demonstrated that E1 was constituted by phenolic and flavonoid compounds, which could be involved in the observed effect. CONCLUSION: This work has proved that the low-cost zebrafish can be an adequate alternative as an animal model to evaluate the anxiolytic effect of C. citratus and its related compounds. Moreover, the involvement of GABAA receptors could be responsible for the effect showed by the samples. These obtained results can potentially validate the ethnopharmacological use of C. citratus as a medicinal plant for the treatment of anxiety disorders in folk medicine.

Essential Oils of Lemongrass (Cymbopogon citratus Stapf) Induces Apoptosis and Cell Cycle Arrest in A549 Lung Cancer Cells.[Pubmed:32420353]

Biomed Res Int. 2020 Jan 11;2020:5924856.

Essential oils were extracted from the culm and leaf of Cymbopogon citratus collected from different regions of Vietnam and analyzed using GC/MS. The results showed that Citral is the major component accounting for 61.20%-76.46% of the essential oils. The Citral content was higher in the essential oil obtained from the leaf than in that from the culm of lemongrass in all regions. In particular, camphene, valerianol, and epi-alpha-muurolol can be used to differentiate essential oils originating from leaves versus culms. The cytotoxic effects of the essential oils on various lung cancer cell lines were evaluated in the present study. All essential oils exhibited cytotoxicity in the tested cells. The Ha Loc leaf essential oil (HLL) exhibited the most potent effects on A549 and H1975 cells, with IC50 values of 1.73 +/- 0.37 and 4.01 +/- 0.30 mug/mL, respectively. The Hy Cuong leaf essential oil (HCL) showed the strongest effect on H1299 cells, with an IC50 value of 2.45 +/- 0.21 mug/mL. The Kim Duc culm (KDC) essential oil exerted the strongest cytotoxic effects against H1650 cells, with an IC50 value of 4.86 +/- 0.29 mug/mL. The HLL induced apoptosis and cycle arrest in A549 cells according to flow cytometric analysis and fluorescent nuclear staining assays. The western blot analysis indicated that HLL induced the apoptotic effect by altering the regulating proteins of the apoptosis process such as caspase-3, Bcl-2, and Bax. The data strongly suggested that the intrinsic pathway may play an important role in the apoptotic effects of HLL.

Lemon Grass Essential Oil Does not Modulate Cancer Cells Multidrug Resistance by Citral-Its Dominant and Strongly Antimicrobial Compound.[Pubmed:32380674]

Foods. 2020 May 5;9(5). pii: foods9050585.

With strong antimicrobial properties, Citral has been repeatedly reported to be the dominant component of lemongrass essential oil. Here, we report on a comparison of the antimicrobial and anticancer activity of Citral and lemongrass essential oil. The lemongrass essential oil was prepared by the vacuum distillation of fresh Cymbopogon leaves, with a yield of 0.5% (w/w). Citral content was measured by gas chromatography/high-resolution mass spectrometry (GC-HRMS) and determined to be 63%. Antimicrobial activity was tested by the broth dilution method, showing strong activity against all tested bacteria and fungi. Citral was up to 100 times more active than the lemongrass essential oil. Similarly, both Citral and essential oils inhibited bacterial communication and adhesion during P. aeruginosa and S. aureus biofilm formation; however, the biofilm prevention activity of Citral was significantly higher. Both the essential oil and Citral disrupted the maturated P. aeruginosa biofilm with the IC50 7.3 +/- 0.4 and 0.1 +/- 0.01 mL/L, respectively. Although it may seem that the Citral is the main biologically active compound of lemongrass essential oil and the accompanying components have instead antagonistic effects, we determined that the lemongrass essential oil-sensitized methicillin-resistant S. aureus (MRSA) and doxorubicin-resistant ovarian carcinoma cells and that this activity was not caused by Citral. A 1 mL/L dose of oil-sensitized MRSA to methicillin up to 9.6 times and a dose of 10 microL/L-sensitized ovarian carcinoma to doxorubicin up to 1.8 times. The mode of multidrug resistance modulation could be due to P-glycoprotein efflux pump inhibition. Therefore, the natural mixture of compounds present in the lemongrass essential oil provides beneficial effects and its direct use may be preferred to its use as a template for Citral isolation.

Proteomic profiling unveils citral modulating expression of IsaA, CodY and SaeS to inhibit biofilm and virulence in methicillin-resistant Staphylococcus aureus.[Pubmed:32360467]

Int J Biol Macromol. 2020 Apr 29. pii: S0141-8130(20)33095-6.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the dangerous human pathogens and it is categorized as a high priority multi-drug resistant bacterium by WHO. Biofilm forming ability of MRSA is responsible for persistent infections and also difficult to eradicate using antibiotic therapy as biofilm is much more resistant to antibiotics. Thus, targeting biofilm and virulence has become an alternative approach to attenuate the pathogenicity of bacterium without affecting the growth. Hence, the present study was aimed at evaluation of antibiofilm potential of Citral against MRSA and to decode the possible mode of action. Citral inhibited biofilm formation by MRSA without affecting growth at 100mug/mL. Microscopic analyses evidenced that Citral greatly hampered the surface adherence of MRSA. Effect of Citral on cellular proteome of MRSA was studied using two-dimensional gel electrophoresis (2DGE) and differentially regulated proteins were identified using nano LC-MS/MS and MALDI-TOF/TOF analysis. Gene ontology and STRING analysis revealed that Citral differentially regulated the proteins involved in pleotropic transcriptional repression (CodY), cell wall homeostasis (IsaA), regulation of exotoxin secretion (SaeS), cell adhesion, hemolysis, capsular polysaccharide biosynthesis and pathogenesis. Gene expression analysis and in vitro assays further validated the alteration in synthesis of slime, hemolysin, lipase, staphyloxanthin and oxidant susceptibility. Thus, the present study unveiled the multiple protein targeted antibiofilm potential of Citral and portrays Citral as a promising therapeutic agent to combat biofilm mediated MRSA infections with less possibility of resistance development.

Physicochemical Properties and Bioactivity of a New Guar Gum-Based Film Incorporated with Citral to Brown Planthopper, Nilaparvata lugens (Stal) (Hemiptera: Delphacidae).[Pubmed:32353929]

Molecules. 2020 Apr 28;25(9). pii: molecules25092044.

The brown planthopper (BPH), Nilaparvata lugens (Stal), is the most notorious rice insect pest. In order to repel BPH effectively while being environmentally friendly, a new film based on guar gum incorporated with Citral (GC film) was formulated. A toxicity bioassay of Citral and guar gum at different proportions (ratios of 3:1, 2:1, 1:1, 1:2, and 1:3 in w/w) of GC film-forming emulsion to BPH was performed with the rice stem dipping method. Results showed that the most effective ratio of Citral to guar gum was 1:1 with the median lethal concentration (LC50) of 4.30 mg/mL, far below the LC50 of guar gum (GG)/Citral individual (141.51 and 44.38 mg/mL, respectively). The mortality of BPH adults and nymphs in the third instar treated with different dilution multiples of GC film-forming emulsion ranged from 46.67% to 82.22% and from 37.78% to 71.11%, respectively. These indicated that GC film-forming emulsion had a direct toxicity on BPH, and the mixture of Citral and GG had synergistic interactions. Subsequently, Fourier-transform infrared spectroscopy showed that the incorporation of guar gum with Citral was successful and did not result in the formation of new chemical bonds. The GC film exhibited a darker color and rougher surface topography with larger apertures and deeper gullies (Ra = 1.42 nm, Rq = 2.05 nm, and Rmax = 25.40 nm) compared to the guar gum film (GG film) (Ra = 1.00 nm, Rq = 1.33 nm, and Rmax = 16.40 nm), as determined by transmission electron microscopy and atomic force microscopy. The GC film exhibited a 50.4% lower solubility in water (30.30% vs. 15.00%) and 71.3% oxygen permeability (8.26 x 10(-9) vs. 2.37 x 10(-9) cm(3)/m(2).d.Pa) (p < 0.05) but did not demonstrate any significant difference in mechanical properties, such as thickness (39.10 vs. 41.70 mm), tensile strength (41.89 vs. 38.30 N/mm(2)), and elongation at break (1.82% vs. 2.03%) (p < 0.05) compared to the GG film. Our findings established a link between physicochemical properties and bioactivity, which can provide useful information on developing and improving GC films and may offer an alternative approach for the control of BPH in the near future.

One-Step Dynamic Imine Chemistry for Preparation of Chitosan-Stabilized Emulsions Using a Natural Aldehyde: Acid Trigger Mechanism and Regulation and Gastric Delivery.[Pubmed:32320613]

J Agric Food Chem. 2020 May 13;68(19):5412-5425.

Chitosan is a polysaccharide widely used as a structuring agent in foods and other materials because of its positive charge (amino groups). At present, however, it is difficult to form and stabilize emulsions using chitosan due to its high hydrophilicity. In this study, oil-in-water emulsions were prepared using a one-pot green-chemistry method. The chitosan and aldehyde molecules were in situ interfacially conjugated during homogenization, which promoted the adsorption of chitosan onto the oil droplet surfaces where they created a protective coating. The universality of this method was verified by using chitosan with different molecular weights and four kinds of natural aldehydes [cinnamaldehyde (CA), Citral (CT), citronella (CN), and vanillin (VL)]. Chitosan with higher molecular weight facilitated the formation of emulsions. By harnessing the dynamic covalent nature of imine bonds, chitosan emulsions with an imine link display dynamic behavior with acid-catalyzed hydrolysis. The aldehyde structure could control the pH point of trigger for breakdown of emulsions, which was 1.0, 3.0, 4.0, and 4.0 for CA emulsion, CT emulsion, CN emulsion, and VL emulsion, respectively. At pH 6.5, aldehyde helped to decrease the interfacial tension of chitosan to about 10 mN/m, while this value would increase if the pH decreased by adding acid during the measurement. Chemical kinetics studies indicated that the hydrophobicity and conjugation effect of the aldehyde together determined the trigger points and properties of the emulsion. Finally, we used the optimized emulsions to encapsulate and control the release of curcumin. The gastric release behavior of the curcumin depended on aldehyde structure: VL > CN > CT approximately CA. Hence, a tailor-made trigger release emulsion system can be achieved by rational selection and design of aldehyde structure to control hydrophobicity and conjugation effect of aldehydes.