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1.
BMC Microbiol ; 24(1): 333, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39251899

ABSTRACT

Pichia kudriavzevii (formerly Candida krusei) poses a significant threat to immunocompromised patients due to its inherent resistance to various antifungal drugs. This study explored the anticandidal potential of citral, linalool, and carvacrol in combination with nystatin against P. kudriavzevii strains.Using the microdilution method following CLSI guidelines, Minimum Inhibitory Concentrations (MICs) and fungicidal concentrations (MFCs) were determined. Citral exhibited MIC values ranging from 50 to 100 µg/ml, averaging 70.24 ± 16.99 µg/ml, while carvacrol had MIC values of 50 to 100 µg/ml, averaging 86.90 ± 16.99 µg/ml. Linalool demonstrated weaker antifungal activity, with MIC values between 100 and 200 µg/ml, averaging 150 ± 38.73 µg/ml. The study assessed the synergistic effectsof these phenols with nystatin through fractional inhibitory concentration indices (FICIS). In addition, flow cytometry was employed to assess apoptosis induction in P. kudriavzevii cells.Carvacrol displayed a remarkable synergistic effect in combination with nystatin against all 21 isolates tested. Conversely, linalool showed synergy in 17 isolates, while citral exhibited synergy in only 2 isolates. These findings highlight distinct patterns of synergy between the different compounds and nystatin against P. kudriavzevii. Also, Carvacrol emerged as the most potent inducer of apoptosis across all P. kudriavzevii strains, followed by citral and linalool. This suggests that carvacrol not only possesses a stronger antifungal effect but also has a more pronounced ability to trigger programmed cell death in P. kudriavzevii. In conclusion, the study supports the potential of carvacrol, citral and linalool, as anticandidal agents, suggesting their supplementation with nystatin for treating P. kudriavzevii infections.


Subject(s)
Acyclic Monoterpenes , Antifungal Agents , Apoptosis , Cymenes , Drug Synergism , Microbial Sensitivity Tests , Monoterpenes , Nystatin , Pichia , Antifungal Agents/pharmacology , Cymenes/pharmacology , Acyclic Monoterpenes/pharmacology , Nystatin/pharmacology , Apoptosis/drug effects , Humans , Monoterpenes/pharmacology , Pichia/drug effects , Pichia/isolation & purification
2.
Parasitol Res ; 123(9): 315, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39227462

ABSTRACT

Mosquito-borne diseases, such as malaria, dengue fever, and the Zika virus, pose significant global health challenges, affecting millions annually. Due to increasing insecticide resistance, there is a growing interest in natural alternatives for mosquito control. Lemongrass essential oil, derived from Cymbopogon citratus, has shown promising repellent and larvicidal properties against various mosquito species. In this study, we investigated the larvicidal effect of lemongrass oil and its major compounds on Anopheles sinensis, the primary malaria vector in China. GC-MS analysis identified the major compounds of lemongrass oil as ( +)-citronellal (35.60%), geraniol (21.84%), and citronellol (13.88%). Lemongrass oil showed larvicidal activity against An. sinensis larvae, with an LC50 value of 119.20 ± 3.81 mg/L. Among the major components, citronellol had the lowest LC50 value of 42.76 ± 3.18 mg/L. Moreover, citronellol demonstrated inhibitory effects on acetylcholinesterase (AChE) activity in An. sinensis larvae, assessed by homogenizing larvae at different time points following treatment. Molecular docking studies further elucidated the interaction between citronellol and AChE, revealing the formation of hydrogen bonds and Pi-Sigma bonds. Aromatic amino acid residues such as Tyr71, Trp83, Tyr370, and Tyr374 played a pivotal role in these interactions. These findings may contribute to understanding lemongrass oil's larvicidal activity against An. sinensis and the mechanisms underlying these effects.


Subject(s)
Acyclic Monoterpenes , Anopheles , Cholinesterase Inhibitors , Insecticides , Larva , Oils, Volatile , Plant Oils , Animals , Anopheles/drug effects , Anopheles/enzymology , Larva/drug effects , Insecticides/pharmacology , Insecticides/chemistry , Acyclic Monoterpenes/pharmacology , Plant Oils/pharmacology , Plant Oils/chemistry , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemistry , Cymbopogon/chemistry , Molecular Docking Simulation , Terpenes/pharmacology , Terpenes/chemistry , Gas Chromatography-Mass Spectrometry , China , Acetylcholinesterase/metabolism , Mosquito Vectors/drug effects , Monoterpenes/pharmacology , Monoterpenes/chemistry , Aldehydes/pharmacology , Aldehydes/chemistry
3.
Food Res Int ; 194: 114917, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39232537

ABSTRACT

Withering is a crucial process that determines the quality of white tea (WT). Solar withering (SW) is reported to contribute to the aroma quality of WT. However, the mechanism by which aroma is formed in WT subjected to SW remains unclear. In this study, through headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and transcriptomics, we found that 13 key genes enriched in the mevalonic acid and methylerythritol phosphate pathways, such as those of 1-deoxy-D-xylulose-5-phosphate synthase and terpineol synthase, were significantly upregulated, promoting the accumulation of α-terpinolene, geraniol, and nerolidol, which imparted floral and fruity odors to WT subjected to SW. Additionally, the significant upregulation of lipoxygenases enriched in the lipoxygenase pathway promoting the accumulation of hexanol, 1-octen-3-ol, (E, Z)-3,6-nonadien-1-ol, and nonanal, which contributed to the green and fresh odor in WT subjected to SW. This study provided the first comprehensive insight into the effect mechanism of SW on aroma formation in WT.


Subject(s)
Gas Chromatography-Mass Spectrometry , Odorants , Solid Phase Microextraction , Odorants/analysis , Tea/chemistry , Volatile Organic Compounds/analysis , Camellia sinensis/chemistry , Camellia sinensis/radiation effects , Terpenes/analysis , Aldehydes/analysis , Gene Expression Regulation, Plant , Acyclic Monoterpenes , Hexanols/analysis , Sesquiterpenes/analysis , Octanols
4.
Acta Parasitol ; 69(3): 1426-1438, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39147955

ABSTRACT

PURPOSE: The flea Ctenocephalides felis (Siphonaptera: Pulicidae), parasitizes dogs and cats globally, acting as a vector for various pathogens affecting both animals and humans. Growing interest in environmentally friendly, plant-based products prompted this study. The aim of the study was to determine the chemical composition of essential oils (EOs) from Copaifera reticulata, Citrus paradisi, Lavandula hybrida and Salvia sclarea, assessing their insecticidal and repellent properties, determining lethal concentrations (LC50 and LC90), and evaluating residual efficacy in vitro against Ctenocephalides felis felis. METHODS: Gas Chromatography with Flame Ionization Detector analyzed EO composition. In vitro tests involved preparing EO solutions at various concentrations. Ten specimens from each life stage (egg, larva, pupa, adult) were used for insecticidal activity assessment. Adulticidal activity was assessed using 10 cm2 filter paper strip, each treated with 0.200 mL of the test solution. Immature stages activities were evaluated using 23.76 cm2 discs of the same filter paper, each treated with 0.470 mL of the test solution. Mortality percentage was calculated using (number of dead insects × 100) / number of incubated insects. Probit analysis calculated LC50 values with a 95% confidence interval. RESULTS: Major EO constituents were ß-caryophyllene (EOCR), linalool (EOLH), linalyl acetate (EOSS), and limonene (EOCP). LC50 values were obtained for all stages except for the essential oil of C. paradisi. All oils showed repellent activity at 800 µg/cm2. OECR exhibited greater residual efficacy. CONCLUSION: Each EO demonstrated superior insecticidal activity against specific C. felis felis stages.


Subject(s)
Ctenocephalides , Insect Repellents , Insecticides , Oils, Volatile , Salvia , Animals , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Salvia/chemistry , Insect Repellents/pharmacology , Insect Repellents/chemistry , Insecticides/pharmacology , Insecticides/chemistry , Ctenocephalides/drug effects , Fabaceae/chemistry , Lavandula/chemistry , Larva/drug effects , Pupa/drug effects , Citrus/chemistry , Acyclic Monoterpenes/pharmacology , Monoterpenes/pharmacology , Monoterpenes/chemistry , Plant Oils/pharmacology , Plant Oils/chemistry , Lethal Dose 50
5.
Molecules ; 29(15)2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39124903

ABSTRACT

This work used headspace solid-phase microextraction with gas chromatography-mass spectrometry (HS-SPME-GC-MS) to analyze the volatile components of hydrosols of Citrus × aurantium 'Daidai' and Citrus × aurantium L. dried buds (CAVAs and CADBs) by immersion and ultrasound-microwave synergistic-assisted steam distillation. The results show that a total of 106 volatiles were detected in hydrosols, mainly alcohols, alkenes, and esters, and the high content components of hydrosols were linalool, α-terpineol, and trans-geraniol. In terms of variety, the total and unique components of CAVA hydrosols were much higher than those of CADB hydrosols; the relative contents of 13 components of CAVA hydrosols were greater than those of CADB hydrosols, with geranyl acetate up to 15-fold; all hydrosols had a citrus, floral, and woody aroma. From the pretreatment, more volatile components were retained in the immersion; the relative contents of linalool and α-terpineol were increased by the ultrasound-microwave procedure; and the ultrasound-microwave procedure was favorable for the stimulation of the aroma of CAVA hydrosols, but it diminished the aroma of the CADB hydrosols. This study provides theoretical support for in-depth exploration based on the medicine food homology properties of CAVA and for improving the utilization rate of waste resources.


Subject(s)
Acyclic Monoterpenes , Citrus , Cyclohexane Monoterpenes , Gas Chromatography-Mass Spectrometry , Solid Phase Microextraction , Volatile Organic Compounds , Gas Chromatography-Mass Spectrometry/methods , Citrus/chemistry , Solid Phase Microextraction/methods , Volatile Organic Compounds/analysis , Volatile Organic Compounds/chemistry , Volatile Organic Compounds/isolation & purification , Acyclic Monoterpenes/analysis , Cyclohexane Monoterpenes/analysis , Terpenes/analysis , Terpenes/chemistry , Monoterpenes/analysis , Monoterpenes/isolation & purification , Odorants/analysis , Distillation/methods , Acetates
6.
Molecules ; 29(15)2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39124986

ABSTRACT

Citrus black spot (CBS) is a fungal disease caused by Phyllosticta citricarpa Kiely, (McAlpine Van der Aa), with most cultivars being susceptible to infection. Currently, disease control is based on the application of protective fungicides, which is restricted due to resistance, health and environmental concerns. Although using natural products for disease management is gaining momentum, more advances are required. This study obtained the metabolic profiles of the essential oil and cuticular waxes of two citrus cultivars with a varying susceptibility to CBS infection using gas chromatography-mass spectrometry. A multivariate data analysis identified possible biomarker compounds that contributed to the difference in susceptibility between the two cultivars. Several identified biomarkers were tested in vitro for their antifungal properties against P. citricarpa. Two biomarkers, propanoic acid and linalool, were able to completely inhibit pathogen growth at 750 mg/L and 2000 mg/L, respectively.


Subject(s)
Ascomycota , Biomarkers , Citrus , Oils, Volatile , Plant Diseases , Plant Diseases/microbiology , Citrus/chemistry , Citrus/microbiology , Ascomycota/chemistry , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Gas Chromatography-Mass Spectrometry , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Acyclic Monoterpenes/pharmacology , Acyclic Monoterpenes/chemistry , Metabolome
7.
J Agric Food Chem ; 72(35): 19395-19402, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39176472

ABSTRACT

ß-Myrcene is an important monoterpene compound widely used in the fragrance, agricultural, and food industries. The microbial production of ß-myrcene conforms to the trend of green biological manufacturing, which has great potential for development. The poor catalytic activity of ß-myrcene synthase (MS) and the insufficient supply of precursors are considered to be the bottlenecks of ß-myrcene production. Here, source screening, subcellular localization, enzyme fusion, and precursor-enhancing strategies were integrated for ß-myrcene biosynthesis with Saccharomyces cerevisiae. The ß-myrcene titer gradually increased by 218-fold (up to 63.59 mg/L) compared to that of the initial titer of the shake flask. Moreover, the titer reached 66.82 mg/L after the addition of antioxidants (1 mM glutathione, GSH, and 1% butylated hydroxytoluene, BHT). Ultimately, 142.64 mg/L ß-myrcene in S. cerevisiae was achieved in 5.0 L of fed-batch fermentation under a carbon restriction strategy, which was the highest reported titer in yeast thus far. This study not only established a platform for ß-myrcene production but also provided a reference for the efficient biosynthesis of other monoterpene compounds.


Subject(s)
Acyclic Monoterpenes , Fermentation , Metabolic Engineering , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae/genetics , Acyclic Monoterpenes/metabolism , Monoterpenes/metabolism , Alkenes/metabolism
8.
Food Chem ; 460(Pt 2): 140361, 2024 Dec 01.
Article in English | MEDLINE | ID: mdl-39098193

ABSTRACT

Strawberries are rich in volatile organic compounds (VOCs), which are increasingly recognized as potential health-promoting factors. This study explored the health effects of intaking strawberry VOC extract and its dominant terpene, linalool. The results indicated that linalool and strawberry VOC extract significantly increased the abundance of beneficial bacteria like Lactobacillus, Bacillus, and Alistipes in mice. Moreover, mice treated with linalool and strawberry VOC extract exhibited notable reductions in serum pro-inflammatory cytokines; interleukin IL-6 decreased by 14.5% and 21.8%, respectively, while IL-1ß levels decreased by 9.6% and 13.4%, respectively. Triglyceride levels in the treated groups were reduced by 38.3% and 58.1%, respectively. Spearman's correlation analysis revealed that Bacillus negatively correlated with glucolipid indices, and Bifidobacterium and Dubosiella negatively correlated with inflammatory factors, indicating that alterations in glucolipid metabolism might be associated with the regulation of gut microbiota and systemic inflammation.


Subject(s)
Acyclic Monoterpenes , Bacteria , Fragaria , Gastrointestinal Microbiome , Inflammation , Volatile Organic Compounds , Animals , Gastrointestinal Microbiome/drug effects , Volatile Organic Compounds/chemistry , Volatile Organic Compounds/metabolism , Mice , Fragaria/chemistry , Fragaria/metabolism , Acyclic Monoterpenes/pharmacology , Acyclic Monoterpenes/metabolism , Male , Bacteria/metabolism , Bacteria/classification , Bacteria/isolation & purification , Inflammation/metabolism , Humans , Plant Extracts/pharmacology , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Interleukin-6/metabolism
9.
Food Chem ; 460(Pt 2): 140578, 2024 Dec 01.
Article in English | MEDLINE | ID: mdl-39106811

ABSTRACT

This investigation employed molten globule state ß-lactoglobulin nanoparticles (MG-BLGNPs) for encapsulating linalool (LN) combined with carboxymethyl chitosan (CMC) coating to enhance the shelf-life of fresh-cut apples. The effect of different MG structures on the encapsulation efficiency of BLGNPs and the properties of coating was studied. Structural characterization and molecular simulation showed structural differences between heat-induced MG state (70-BLGNPs, heated at 70 °C for 1 h) and sodium dodecyl sulfate-co-heat-induced MG state (SDS/70-BLGNPs, treated with 0.192 mg/mL SDS for 10 min, then heated at 70 °C for 1 h), with the latter being more unfolded. LN self-assembles into MG-BLGNPs, among the generated particles, SDS/70-BLG@LN exhibits stronger binding effect and higher LN loading capacity. Integration of MG-BLG@LN into CMC enhanced coating's mechanical properties and adhesion to fresh-cut apples. The SDS/70-BLG@LN/CMC coating showed superior preservation on fresh-cut apples during storage, reducing enzymatic browning, membrane lipid oxidation, and microbial growth while maintaining hardness and overall quality.


Subject(s)
Acyclic Monoterpenes , Chitosan , Food Preservation , Lactoglobulins , Malus , Nanoparticles , Chitosan/chemistry , Chitosan/analogs & derivatives , Acyclic Monoterpenes/chemistry , Acyclic Monoterpenes/pharmacology , Malus/chemistry , Nanoparticles/chemistry , Food Preservation/methods , Lactoglobulins/chemistry , Fruit/chemistry
10.
Braz Oral Res ; 38: e071, 2024.
Article in English | MEDLINE | ID: mdl-39109768

ABSTRACT

This is a nonclinical, controlled, and triple-blind study to investigate the effects of codeine-associated geraniol on the modulation of orofacial nociception and its potential central nervous system depressing effect in an animal model. The orofacial antinociceptive activity of geraniol in combination with codeine was assessed through the following tests: (i) formalin-induced pain, (ii) glutamate-induced pain, and (iii) capsaicin-induced pain. Six animals were equally distributed into six groups and received the following treatments, given intraperitoneally (i.p.) 30 minutes before the experiments: a) geraniol/codeine 50/30 mg/kg; b) geraniol/codeine 50/15 mg/kg; c) geraniol/codeine 50/7.5 mg/kg; d) geraniol 50 mg/kg; e) codeine 30 mg/kg (positive control); or f) 0.9% sodium chloride (negative control). We performed pain behavior analysis after the injection of formalin (20 µL, 20%), glutamate (20 µL, 25 µM), and capsaicin (20 µL, 2.5 µg) into the paranasal region. Rubbing time of the paranasal region by the hind or front paw was used as a parameter. In the neurogenic phase of the formalin test, the geraniol/codeine at 50/7.5 mg/kg was able to promote the maximum antinociceptive effect, reducing nociception by 71.9% (p < 0.0001). In the inflammatory phase of the formalin test, geraniol/codeine at 50/30 mg/kg significantly reduced orofacial nociception (p < 0.005). In the glutamate test, geraniol/codeine at 50/30 mg/kg reduced the rubbing time by 54.2% and reduced nociception in the capsaicin test by 66.7% (p < 0.005). Geraniol alone or in combination does not promote nonspecific depressing effects on the central nervous system. Based on our findings, we suggest the possible synergy between geraniol and codeine in the modulation of orofacial pain.


Subject(s)
Acyclic Monoterpenes , Analgesics , Capsaicin , Codeine , Facial Pain , Pain Measurement , Terpenes , Animals , Codeine/pharmacology , Facial Pain/chemically induced , Facial Pain/drug therapy , Acyclic Monoterpenes/pharmacology , Male , Pain Measurement/drug effects , Capsaicin/pharmacology , Terpenes/pharmacology , Analgesics/pharmacology , Mice , Time Factors , Disease Models, Animal , Reproducibility of Results , Formaldehyde , Glutamic Acid , Treatment Outcome , Nociception/drug effects , Analysis of Variance , Statistics, Nonparametric , Behavior, Animal/drug effects
11.
Molecules ; 29(15)2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39125074

ABSTRACT

Chardonnay is one of the most popular white grape wine varieties in the world, but this wine lacks typical aroma, considered a sensory defect. Our research group identified a Chardonnay bud sport with typical muscat characteristics. The goal of this work was to discover the key candidate genes related to muscat characteristics in this Chardonnay bud sport to reveal the mechanism of muscat formation and guide molecular design breeding. To this end, HS-SPME-GC-MS and RNA-Seq were used to analyze volatile organic compounds and the differentially expressed genes in Chardonnay and its aromatic bud sport. Forty-nine volatiles were identified as potential biomarkers, which included mainly aldehydes and terpenes. Geraniol, linalool, and phenylacetaldehyde were identified as the main aroma components of the mutant. The GO, KEGG, GSEA, and correlation analysis revealed HMGR, TPS1, TPS2, TPS5, novel.939, and CYP450 as key genes for terpene synthesis. MAO1 and MAO2 were significantly downregulated, but there was an increased content of phenylacetaldehyde. These key candidate genes provide a reference for the development of functional markers for muscat varieties and also provide insight into the formation mechanism of muscat aroma.


Subject(s)
Metabolome , Odorants , Transcriptome , Volatile Organic Compounds , Odorants/analysis , Volatile Organic Compounds/metabolism , Volatile Organic Compounds/analysis , Vitis/genetics , Vitis/chemistry , Vitis/metabolism , Wine/analysis , Terpenes/metabolism , Gene Expression Profiling , Acyclic Monoterpenes/metabolism , Gene Expression Regulation, Plant , Gas Chromatography-Mass Spectrometry , Acetaldehyde/analogs & derivatives , Acetaldehyde/metabolism , Monoamine Oxidase/genetics , Monoamine Oxidase/metabolism
12.
Int J Biol Macromol ; 277(Pt 3): 134154, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39116822

ABSTRACT

This work aimed to explore an alternative to the use of antibiotics for prevention and treatment of wounds infection caused by two common bacterial pathogens Staphylococcus aureus and Pseudomonas aeruginosa. For this purpose, three different essential oil components (EOCs), namely carvacrol, citronellol and cinnamic acid, were loaded into electrospun fibers of poly-ε-caprolactone (PCL) aided by alpha-cyclodextrin (αCD) and hydroxypropyl-ß-cyclodextrin (HPßCD). Electrospun-fibers prepared with each EOC and their mixtures were screened for antimicrobial capability and characterized regarding morphological, mechanical, thermal, surface polarity, antibiofilm and antioxidant properties. αCD formed poly(pseudo)rotaxanes with PCL and weakly interacted with EOCs, while HPßCD facilitated EOC encapsulation and formation of homogeneous fibers (500-1000 nm diameter) without beads. PCL/HPßCD fibers with high concentration of EOCs (mainly carvacrol and cinnamic acid) showed strong antibiofilm (>3 log CFU reduction) and antioxidant activity (10-50% DPPH scavenging effects). Different performances were recorded for the EOCs and their mixtures; cinnamic acid migrated to fiber surface and was released faster. Fibers biocompatibility was verified using hemolysis tests and in ovo tissue integration and angiogenesis assays. Overall, HPßCD facilitates complete release of EOCs from the fibers to the aqueous medium, being an environment-friendly and cost-effective strategy for the treatment of infected wounds.


Subject(s)
Acyclic Monoterpenes , Antioxidants , Cinnamates , Cymenes , Monoterpenes , Wound Healing , Wound Healing/drug effects , Cymenes/pharmacology , Cymenes/chemistry , Cinnamates/chemistry , Cinnamates/pharmacology , Acyclic Monoterpenes/pharmacology , Acyclic Monoterpenes/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Monoterpenes/pharmacology , Monoterpenes/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Staphylococcus aureus/drug effects , Cyclodextrins/chemistry , Cyclodextrins/pharmacology , Biofilms/drug effects , Nanofibers/chemistry , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Polyesters/chemistry , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Pseudomonas aeruginosa/drug effects
13.
Acta Trop ; 258: 107356, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39128617

ABSTRACT

Tropical and subtropical regions face millions of deaths from mosquito-borne illnesses yearly. Insecticides prevent transmission but pose health risks like dermatitis and allergies. The primary objective was to mitigate the recurring dependence on synthetic insecticides, thereby curbing the development of mosquito resistance. Leaves of Cymbopogon flexuosus (lemongrass) was collected from Mayurbhanj, India, processed, then extracted by steam distillation for essential oils & analyzed spectroscopically. Larvicidal assays were performed across varying concentrations, revealing the significant mortality induced by the Cymbopogon flexuosus extract against Anopheles stephensi larvae. 3D structure was modelled by using G protein-coupled receptors (GPCR) sequence and structural stability was also validated. After docking the binding free energy was determined from GPCR protein with ß-citral complex. Molecular dynamics (MD) study was conducted on the docked pose that displayed an optimal interactome profile. The larvicidal assay at the 12th and 24th hour revealed the highest LC50 (lethal concentration) of 23.493 ppm and 19.664 ppm . ß-Citral has a high binding affinity and an identifiable binding site, which suggests that it may play a larvicidal role in regulating the receptor's function by creating stable complexes with it. ß-Citral from lemongrass oils has potential larvicidal activity and effective against GPCR family 1 of mosquito and highly effective repellents against mosquito-borne diseases.


Subject(s)
Anopheles , Cymbopogon , Insecticides , Larva , Molecular Docking Simulation , Molecular Dynamics Simulation , Animals , Larva/drug effects , Insecticides/pharmacology , Insecticides/chemistry , Anopheles/drug effects , Cymbopogon/chemistry , India , Plant Leaves/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Acyclic Monoterpenes/pharmacology , Acyclic Monoterpenes/chemistry , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Receptors, G-Protein-Coupled/metabolism
14.
Acta Trop ; 258: 107359, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39142548

ABSTRACT

With growing interest in natural compounds as alternative mosquito repellents, assessing the toxicity and structure of potential repellent naturals like thymol (monoterpene phenol) and geraniol (monoterpene alcohol) is vital for understanding their stability and human impact. This study aimed to determine the structural, toxicity, and binding profiles of thymol and geraniol using computational predictions, xTB metadynamics, quantum mechanics, and principal component analysis. Toxicity studies using Protox-II, T.E.S.T, and SwissADME indicated that thymol and geraniol belong to toxicity class 4 and 5, respectively, with low toxicity predictions in other endpoints. Overall pharmacokinetic profile was generated via pkCSM. Off-target predictions via SwissTarget Predictions, LigTMap, Pharmapper, and SuperPred showed that these molecules can bind to 614 human proteins. The degradation of thymol and geraniol were performed using xTB metadynamics and the outcomes showed that the degradants for both compounds were stable and had lower toxicity profile. Nine tautomers were generated via quantum mechanics for thymol and four for geraniol, with RMSD ranging from 3.8 to 6.3 Å for thymol and 3.6 to 4 Å for geraniol after superimpositions. DFT studies found that HOMO-LUMO values and electronegativity parameters of thymol and geraniol did not differ significantly from their isomers. Binding affinity studies against 614 proteins, analysed via PCA and violin plots, highlighted the probable range of binding. These multifaceted in-silico findings corroborate the stability and potential utility of thymol and geraniol as safer alternatives in repellent applications.


Subject(s)
Acyclic Monoterpenes , Insect Repellents , Proteome , Thymol , Thymol/chemistry , Thymol/pharmacology , Humans , Acyclic Monoterpenes/chemistry , Insect Repellents/chemistry , Insect Repellents/pharmacology , Quantum Theory , Terpenes/chemistry
15.
Int J Mol Sci ; 25(16)2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39201605

ABSTRACT

Acute myelogenous leukemia (AML) is one of the most lethal cancers, lacking a definitive curative therapy due to essential constraints related to the toxicity and efficacy of conventional treatments. This study explores the co-adjuvant potential of Lippia alba essential oils (EO) for enhancing the effectiveness and selectivity of two chemotherapy agents (cytarabine and clofarabine) against AML cells. EO derived from L. alba citral chemotype were produced using optimized and standardized environmental and extraction protocols. Rational fractionation techniques were employed to yield bioactive terpene-enriched fractions, guided by relative chemical composition and cytotoxic analysis. Pharmacological interactions were established between these fractions and cytarabine and clofarabine. The study comprehensively evaluated the cytotoxic, genotoxic, oxidative stress, and cell death phenotypes induced by therapies across AML (DA-3ER/GM/EVI1+) cells. The fraction rich in citral (F2) exhibited synergistic pharmacological interactions with the studied chemotherapies, intensifying their selective cytotoxic, genotoxic, and pro-oxidant effects. This shift favored transitioning from necrosis to a programmed cell death phenotype (apoptotic). The F2-clofarabine combination demonstrated remarkable synergistic anti-leukemic performance while preserving cell integrity in healthy cells. The observed selective antiproliferative effects may be attributed to the potential dual prooxidant/antioxidant behavior of citral in L. alba EO.


Subject(s)
Acyclic Monoterpenes , Lippia , Oils, Volatile , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Lippia/chemistry , Acyclic Monoterpenes/pharmacology , Humans , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Cytarabine/pharmacology , Leukemia, Myeloid, Acute/drug therapy , Clofarabine/pharmacology , Apoptosis/drug effects , Drug Synergism , Oxidative Stress/drug effects , Cell Proliferation/drug effects
16.
Int J Mol Sci ; 25(14)2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39063231

ABSTRACT

Chemical residues in food pose health risks such as cancer and liver issues. This has driven the search for safer natural alternatives to synthetic fungicides and preservatives. The aim of this study was to characterize the chemical composition of the essential oils (EO), determine the polyphenolic contents, and evaluate the in vitro antioxidant and antifungal activities of methanol extracts (ME), essential oils (EO), and powders from Rosmarinus officinalis L. (rosemary) and Thymus ciliatus (Desf) Benth. (thyme) from the M'sila region, Algeria. The chemical composition of the EOs was determined by GC-MS. R. officinalis EO was composed of 31 components, mainly camphor (41.22%), camphene (18.14%), and α-pinene (17.49%); T. ciliatus EO was composed of 58 components, mainly, in percentage, α-pinene (22.18), myrcene (13.13), ß-pinene (7.73), ß-caryophyllene (10.21), and germacrene D (9.90). The total phenols and flavonoids were determined spectrophotometrically, and the rosemary ME was found to possess the highest polyphenolic content (127.1 ± 2.40 µg GAE/mg), while the thyme ME had the highest flavonoid content (48.01 ± 0.99 µg QE/mg). The antioxidant activity was assessed using three methods: rosemary ME was the most potent, followed by DPPH (IC50 = 13.43 ± 0.14 µg/mL), ß-carotene/linoleic acid (IC50 = 39.01 ± 2.16 µg/mL), and reducing power (EC50 = 15.03 ± 1.43 µg/mL). Antifungal activity was assessed for 32 pathogenic and foodborne fungi. Four methods were applied to the solid medium. Incorporating the powdered plant into the culture medium (at 10%) reduced the fungal growth to greater than 50% in 21.88% and 6.25% of all fungal isolates, for R. officinalis and T. ciliatus, respectively. The ME, applied by the well diffusion method (0.1 g/mL), was less effective. Different concentrations of EO were tested. Incorporating the EO into the culture medium (1500 µL/L) inhibited 50% of the molds to levels of 50 and 75% for R. officinalis and T. ciliatus, respectively, with the complete inhibition of four fungi. Fumigated EO (15 µL) inhibited 65% of the molds to levels of 65 and 81.25% for R. officinalis and T. ciliatus, respectively, with the complete inhibition of five fungi. There was little to no sporulation in conjunction with the inhibition. Our results revealed some of the potential of the studied plants to fight foodborne molds and presented their promising characteristics as a source of alternatives to chemical pesticides and synthetic preservatives. Further studies are needed to find adequate application techniques in the food safety area.


Subject(s)
Antifungal Agents , Antioxidants , Oils, Volatile , Plant Extracts , Rosmarinus , Thymus Plant , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Thymus Plant/chemistry , Rosmarinus/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Phytochemicals/pharmacology , Phytochemicals/chemistry , Phytochemicals/analysis , Bicyclic Monoterpenes/pharmacology , Bicyclic Monoterpenes/chemistry , Methanol/chemistry , Powders , Acyclic Monoterpenes/pharmacology , Monoterpenes/pharmacology , Monoterpenes/analysis , Monoterpenes/chemistry , Camphor/pharmacology , Camphor/analysis , Camphor/chemistry , Alkenes
17.
Biomolecules ; 14(7)2024 Jul 05.
Article in English | MEDLINE | ID: mdl-39062514

ABSTRACT

Liver fibrosis, a consequence of chronic liver damage or inflammation, is characterized by the excessive buildup of extracellular matrix components. This progressive condition significantly raises the risk of severe liver diseases like cirrhosis and hepatocellular carcinoma. The lack of approved therapeutics underscores the urgent need for novel anti-fibrotic drugs. Hepatic stellate cells (HSCs), key players in fibrogenesis, are promising targets for drug discovery. This study investigated the anti-fibrotic potential of Citrus hystrix DC. (KL) and its bioactive compound, ß-citronellol (ß-CIT), in a human HSC cell line (LX-2). Cells exposed to TGF-ß1 to induce fibrogenesis were co-treated with crude KL extract and ß-CIT. Gene expression was analyzed by real-time qRT-PCR to assess fibrosis-associated genes (ACTA2, COL1A1, TIMP1, SMAD2). The release of matrix metalloproteinase 9 (MMP-9) was measured by ELISA. Proteomic analysis and molecular docking identified potential signaling proteins and modeled protein-ligand interactions. The results showed that both crude KL extract and ß-CIT suppressed HSC activation genes and MMP-9 levels. The MAPK signaling pathway emerged as a potential target of ß-CIT. This study demonstrates the ability of KL extract and ß-CIT to inhibit HSC activation during TGF-ß1-induced fibrogenesis, suggesting a promising role of ß-CIT in anti-hepatic fibrosis therapies.


Subject(s)
Acyclic Monoterpenes , Hepatic Stellate Cells , Liver Cirrhosis , Transforming Growth Factor beta1 , Humans , Actins , Antifibrotic Agents/pharmacology , Cell Line , Collagen Type I/metabolism , Collagen Type I/genetics , Collagen Type I, alpha 1 Chain , Hepatic Stellate Cells/drug effects , Hepatic Stellate Cells/metabolism , Liver Cirrhosis/drug therapy , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase 9/genetics , Molecular Docking Simulation , Smad2 Protein/metabolism , Smad2 Protein/genetics , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tissue Inhibitor of Metalloproteinase-1/genetics , Transforming Growth Factor beta1/pharmacology , Acyclic Monoterpenes/pharmacology
18.
Curr Biol ; 34(15): 3550-3563.e8, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39043188

ABSTRACT

It is unknown why roses are terpene-rich, what the terpene biosynthetic pathways in roses are, and why only a few rose species produce the major components of rose essential oil. Here, we assembled two high-quality chromosome-level genomes for Rosa rugosa and Rosa multiflora. We also re-sequenced 132 individuals from the F1 progeny of Rosa chinensis and Rosa wichuraiana and 36 of their related species. Comparative genomics revealed that expansions of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) and terpene synthases (TPSs) gene families led to the enrichment of terpenes in rose scent components. We constructed a terpene biosynthesis network and discovered a TPS-independent citronellol biosynthetic pathway in roses through gene functional identification, genome-wide association studies (GWASs), and multi-omic analysis. Heterologous co-expression of rose citronellol biosynthetic genes in Nicotiana benthamiana led to citronellol production. Our genomic and metabolomic analyses suggested that the copy number of NUDX1-1a determines the citronellol content in different rose species. Our findings not only provide additional genome and gene resources and reveal the evolution of the terpene biosynthetic pathways but also present a nearly complete scenario for terpenoid metabolism that will facilitate the breeding of fragrant roses and the production of rose oil.


Subject(s)
Biosynthetic Pathways , Rosa , Terpenes , Rosa/genetics , Rosa/metabolism , Terpenes/metabolism , Biosynthetic Pathways/genetics , Alkyl and Aryl Transferases/genetics , Alkyl and Aryl Transferases/metabolism , Genome-Wide Association Study , Odorants , Evolution, Molecular , Genome, Plant , Acyclic Monoterpenes/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism
19.
J Food Sci ; 89(8): 4823-4838, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39030755

ABSTRACT

Citrus species have undergone immense diversification ever since their ancestral origin. Ponkan and Murcott are two mandarin varieties widely consumed in Brazil and their aroma producing active compounds have not yet been extensively investigated. The present study analyzed the volatile constituents of the Ponkan and Murcott varieties employing the stir bar sorptive extraction (SBSE) technique and gas chromatography-mass spectrometry (GC-MS) analysis for the first time. Extraction was performed using the two phases of Twister bar, polydimethyl siloxane (PDMS), and ethylene glycol (EG) silicone in immersion and headspace modes. Among the detected 62 compounds comprising alcohols, aldehydes, esters, terpenes, and others identified, 55 and 37 compounds in the Ponkan and Murcott variety were determined, respectively, from both immersion and headspace modes using the two phases of Twister bar. From the odor active values, the Ponkan was characterized with the domination of compounds such as hexanal, decanal, nonanal, (E)-2-hexanal, ethyl hexanoate, d-limonene, linalool, and geraniol. Similarly, the Murcott variety was characterized with predominant compounds, namely, nonanal, octanal, hexanal, (E)-2-hexanal, ethyl hexanoate, d-limonene, and linalool. The profile of volatile compounds was found to be unique in both the varieties studied, and SBSE technique with GC-MS analysis favored the characterization of their respective profile due to the high amount of phase in the Twister bars, when compared to similar techniques, like solid phase microextraction. The PDMS Twister bar showed better capacity of adsorption of volatile compounds, since it is a relatively low-polarity polymer, which discriminates less analytes with different structures and polarities sampled from complex matrices, such as fruits juice.


Subject(s)
Citrus , Fruit , Gas Chromatography-Mass Spectrometry , Odorants , Volatile Organic Compounds , Volatile Organic Compounds/analysis , Gas Chromatography-Mass Spectrometry/methods , Odorants/analysis , Fruit/chemistry , Citrus/chemistry , Brazil , Aldehydes/analysis , Acyclic Monoterpenes/analysis
20.
Environ Sci Pollut Res Int ; 31(35): 47598-47610, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38997599

ABSTRACT

Sodium chloride (NaCl) can cause oxidative stress in plants, which represents a potential obstacle to the development of monocultures worldwide. Onion (Allium cepa L.) is a famous vegetable consumed and used in world cuisine. In the present study, we analyzed the influence of soil physicochemical profile and the remedial capacity of linalool on seed emergence, roots, and leaf growth in onions subjected to salt stress, as well as its in vivo and in vitro antioxidant potential, Fe2+chelating activity, and reducing power of Fe3+. The outcome of the soil analysis established the following order of abundance: sulfur (S) > calcium (Ca) > potassium (K) > magnesium (Mg) > sodium (Na). NaCl (150 mM) significantly reduced the emergence speed index (ESI), leaf and root length, while increasing the peroxidation content. The length of leaves and roots significantly increased after treatment with linalool (300 and 500 µg/mL). Our data showed negative correlations between seed emergence and K+ concentration, which was reversed after treatments. Linalool (500 µg/mL) significantly reduced oxidative stress, but increased Fe2+ concentration and did not show potential to reduce Fe3+. The in vivo antioxidant effect of linalool is thought to primarily result from an enzymatic activation process. This mechanism underscores its potential as a therapeutic agent for oxidative stress-related conditions. Further investigation into this process could unveil new avenues for antioxidant therapy.


Subject(s)
Acyclic Monoterpenes , Antioxidants , Onions , Onions/drug effects , Acyclic Monoterpenes/pharmacology , Salt Stress/drug effects , Monoterpenes/pharmacology , Oxidative Stress/drug effects
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