RESUMEN
Different species of aphids, responsible for severe yield losses of cereal crops including wheat, (Triticum aestivum L.) are managed by insecticides, which are harmful to organisms and the environment under field conditions. Therefore, an environment friendly aphidicidal product of plant origin is required. Mentha spicata oil was found to be rich in carvone (81.88%), but the use of its oil and carvone in crop protection is lacking due to their volatility, poor solubility, and stability. A nanoformulaton not only solves these problems but also improve the efficacy and dose of the bioactive compounds. Thus, nano-emulsions of the oil and carvone prepared were characterized, and evaluated against Rhopalosiphum maidis (corn aphid) and Sitobion avenae (wheat aphid) The average droplet size of nano-emulsions of the oil and carvone was found to be 22.1 and 41.21 nm. Nano-emulsion of carvone exhibited higher aphid mortality (LC50 = 0.87-1.94 mg/mL) at 24 h and acetylcholinesterase inhibitory activity (IC50 = 0.07-3.83 mg/mL) compared to the nano-emulsion of the oil (LC50 = 2.87-2.81 mg/mL; IC50 = 1.66-5.34 mg/mL). The repellence index (RI) in nano-emulsion of essential oil was found to be higher (84.73 and 81.72%) at the highest concentration (0.05 µL/cm2) than that of carvone (77.59 and 80.98%) for R. maidis and S. avenae. Further, in silico studies also revealed the favourable binding energy (- 6.6 to - 8.5 kcal/mol) of the main compounds in the oil with acetylcholinesterase, facilitated by hydrophobic interactions and hydrogen bonding. This study suggests that the nano-emulsions of the essential oil and carvone can be explored under field conditions to establish efficacy for their utilization as aphidicidal and repellent products against aphids. In the present study, aphidicial and repellent activities of its essential oil and carvone were reported for the first time against R.maidis and S.avenae.
Asunto(s)
Áfidos , Monoterpenos Ciclohexánicos , Emulsiones , Insecticidas , Animales , Áfidos/efectos de los fármacos , Emulsiones/química , Monoterpenos Ciclohexánicos/farmacología , Monoterpenos Ciclohexánicos/química , Insecticidas/farmacología , Insecticidas/química , Mentha/química , Aceites de Plantas/farmacología , Aceites de Plantas/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Acetilcolinesterasa/metabolismoRESUMEN
Macrocyclic natural products, particularly those with no functionalities except unsaturation, are recognized for their therapeutic potential but are notoriously challenging to synthesize. In this study, we report the first total synthesis of an unconventional 18-membered, C25 macrocyclic terpenoid, which has demonstrated substantial immunosuppressive activity. This synthesis was achieved through strategic modifications and innovative reaction engineering, utilizing α-terpineol and geraniol as starting materials, highlighting a novel approach in macrocyclic terpenoid synthesis.
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Transferasas Alquil y Aril , Inmunosupresores , Terpenos , Terpenos/química , Terpenos/síntesis química , Transferasas Alquil y Aril/metabolismo , Transferasas Alquil y Aril/antagonistas & inhibidores , Inmunosupresores/química , Inmunosupresores/síntesis química , Inmunosupresores/farmacología , Compuestos Macrocíclicos/química , Compuestos Macrocíclicos/síntesis química , Estructura Molecular , Monoterpenos Acíclicos , Monoterpenos CiclohexánicosRESUMEN
Carvone, a natural monoterpene, has been identified in various plants, giving them a characteristic scent. Enantiomers (R-(-) and S-(+)) reveal specific biological activities that are successfully used in traditional medicine for their antifungal, antibacterial, antiparasitic, and anti-influenza properties. The presented paper is based on S-(+)-carvone, characterized by a specific caraway scent, which revealed rich biological activities both in vitro and in vivo. Thus, the aim of the study was to evaluate the potential anti-neurodegenerative activity of S-(+)-carvone, including in vitro experiments (butyrylcholinesterase inhibitory, neuro- and hepatotoxicity as well as neuro- and hepatoprotective activity), in vivo (memory acquisition, locomotor activity), and ex vivo (determination of S-(+)-carvone's level in tissues collected from mice). Results revealed the multidirectional character of S-(+)-carvone. It has been shown that S-(+)-carvone is capable of butyrylcholinesterase inhibition (40% for 0.025 mg applied onto the plate), and neuroprotection and hepatoprotection at selective concentrations against reactive oxygen species generation and lipid peroxidation along with non-hepatotoxicity character. Additionally, multiple-dose administration of the monoterpene at a dose of 100 mg/kg had a positive influence on memory acquisition. Gas chromatography-mass spectrometry analysis of the plasma and the brain showed that S-(+)-carvone can cross the blood-brain barrier and accumulate in the hippocampus (0.217 µg/mg of tissue), a crucial part of the brain associated with cognition and mental functions.
Asunto(s)
Monoterpenos Ciclohexánicos , Fármacos Neuroprotectores , Animales , Ratones , Monoterpenos Ciclohexánicos/farmacología , Monoterpenos Ciclohexánicos/química , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Monoterpenos/farmacología , Monoterpenos/química , Masculino , Butirilcolinesterasa/metabolismo , HumanosRESUMEN
The deterioration of aroma quality in tea beverages during the shelf life is a significant issue. In this study, sensomics techniques were employed to identify the characteristic factor contributing to aroma degradation in green tea infusion. Samples A (no/faint retort odor) and B (high intensity retort odor) were selected based on their retort-like odor intensity after heat treatment simulating shelf-life conditions. The key odorants were identified through a combination of chemometrics analysis, comparative aromatic extract dilution analysis (cAEDA), detection frequency analysis (DFA), and odor-specific magnitude estimation (OSME). Subsequently, eight odorants, including linalool (892.451 µg/L), (E)-ß-damascenone (5.105 µg/L), phenylacetaldehyde (27.720 µg/L), nonanal (2201.439 µg/L), α-terpineol (7.166 µg/L), geraniol (0.499 µg/L), theaspirane (0.044 µg/L), and 2-hydroxy-5-methylacetophenone (2.973 µg/L), were identified as the key substances contributing to the retort-like odor in sample B. Aroma recombination and omission test further demonstrated that elevated concentrations of nonanal, geraniol, phenylacetaldehyde, and theaspirane might be the primary reasons for the retort odor observed in samples.
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Monoterpenos Acíclicos , Odorantes , Té , Odorantes/análisis , Té/química , Monoterpenos Acíclicos/análisis , Almacenamiento de Alimentos/métodos , Compuestos Orgánicos Volátiles/análisis , Cromatografía de Gases y Espectrometría de Masas , Acetaldehído/análisis , Acetaldehído/análogos & derivados , Monoterpenos Ciclohexánicos/análisis , Terpenos/análisis , Ciclohexenos/análisis , Calor , NorisoprenoidesRESUMEN
Plant essential oils (EOs)-based acaricides have been recognized as environmentally-friendly alternatives to synthetic acaricides because of their low toxicity against non-target species. Despite this, there are knowledge gaps regarding the toxicity mechanisms of plant EOs against non-target species. Here, the toxicology and enzymatic mechanism of Citrus reticulata and Citrus lemon EOs were evaluated against the vector pest, Haemaphysalis longicornis, and non-target ladybird beetle, Harmonia axyridis. Both EOs were mainly composed of d-Limonene, followed by ß-Myrcene and γ-Terpinene in C. reticulata, and (-)-ß-Pinene and γ-Terpinene in C. lemon. Citrus reticulata and C. lemon EOs were toxic to Hae. longicornis, with 50 % lethal concentration (LC50) values estimated at 0.43 and 0.98 µL/mL via nymphal immersion test, and 42.52 and 46.38 µL/mL via spray application, respectively. Among the constituents tested, ß-Myrcene was the most effective, with LC50 values of 0.17 and 47.87 µL/mL via immersion and spray treatment, respectively. A significant mortality of non-target Har. axyridis was found when treated by the EOs at concentrations two times greater than LC50 estimated against H. longicornis. The biochemical assay revealed that the EOs induced changes in the antioxidant enzyme activity of superoxide dismutases, catalase, and glutathione peroxidase in Hae. longicornis and Har. axyridis. The results demonstrated the acaricidal potential of citrus EOs and their major constituents for tick control, revealed the risk of the EOs to non-target species, and provided relevant insights into the mechanisms underlying their toxicity.
Asunto(s)
Acaricidas , Citrus , Escarabajos , Ixodidae , Aceites Volátiles , Animales , Aceites Volátiles/farmacología , Aceites Volátiles/toxicidad , Escarabajos/efectos de los fármacos , Ixodidae/efectos de los fármacos , Ixodidae/enzimología , Acaricidas/farmacología , Acaricidas/toxicidad , Monoterpenos Ciclohexánicos , Monoterpenos Bicíclicos/farmacología , Monoterpenos Acíclicos/toxicidad , Monoterpenos Acíclicos/farmacología , Limoneno/farmacología , Monoterpenos/farmacología , Monoterpenos/toxicidad , Ciclohexenos/toxicidad , Ciclohexenos/farmacología , Terpenos/farmacología , Catalasa/metabolismo , Superóxido Dismutasa/metabolismo , Glutatión Peroxidasa/metabolismo , Antioxidantes/farmacología , Haemaphysalis longicornisRESUMEN
Reticulitermes flaviceps is an economically important pest in agriculture, forestry, and construction. Recent studies have shown an increase in research focusing on the anti-termite properties of plant essential oils, however, there remains a lack of information regarding the specific molecular mechanism involved. In this study, RNA-seq analysis was conducted on termites exposed to Mentha spicata essential oil (EO) and carvone, leading to the discovery of various genes that were expressed differentially under different treatment conditions. Numerous genes that exhibited a response to M. spicata EO and carvone found to be associated with stress-related pathways, such as drug metabolism cytochrome P450, glutathione metabolism, fatty acid metabolism, citric acid cycle, neuroactive ligand-receptor interaction, cell apoptosis, the AMPK signalling pathway, the mTOR signalling pathway, the longevity regulation pathway, ubiquitin-mediated protein hydrolysis, and the calcium signalling pathway. The up-regulation of genes (SPHK) associated with calcium channels, such as SPHK, indicates a potential mechanism of neurotoxicity, while the up-regulation of apoptosis-associated genes, including ACTB_G1, PYG, SQSTM1, RNF31, suggests a potential mechanism of cytotoxicity. The metabolism of M. spicata EO induces oxidative stress, elevates free Ca2+ levels in mitochondria, and initiates the generation of reactive oxygen species (ROS), ultimately resulting in programmed cell necrosis and apoptosis, as well as facilitating cellular autophagy. The monoterpenes exhibited neurotoxic and cytotoxic effects on R. flaviceps and could be exploited to advance termiticide development and eco-friendly termite control.
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Calcio , Monoterpenos Ciclohexánicos , Isópteros , Mentha spicata , Aceites Volátiles , Animales , Calcio/metabolismo , Mentha spicata/metabolismo , Isópteros/efectos de los fármacos , Isópteros/genética , Perfilación de la Expresión Génica , Transcriptoma/efectos de los fármacos , Monoterpenos/farmacología , Monoterpenos/toxicidad , Apoptosis/efectos de los fármacosRESUMEN
Aspergillus carbonarius, a common food-contaminating fungus, produces ochratoxin A (OTA) and poses a risk to human health. This study aimed to assess the inhibitory activity of tea tree essential oil and its main components, Terpene-4-ol (T4), α-terpineol (αS), and 3-carene (3C) against A. carbonarius. The study showed αS and T4 were the main antifungal components of tea tree essential oil, which primarily inhibit A. carbonarius growth through cell membrane disruption, reducing antioxidant enzyme activities (catalase, peroxidase, superoxide dismutase) and interrupting the tricarboxylic acid cycle. Furthermore, αS and T4 interacted with enzymes related to OTA biosynthesis. Molecular docking and molecular dynamics show that they bound mainly to P450 with a minimum binding energy of -7.232 kcal/mol, we infered that blocking the synthesis of OTA precursor OTß. Our hypothesis was preliminarily verified by the detection of key substances in the OTA synthesis pathway. The results of UHPLC-QTOF-MS2 analysis demonstrated that T4 achieved a degradation rate of 43 % for OTA, while αS reached 29.6 %, resulting in final breakdown products such as OTα and phenylalanine. These results indicated that α-terpinol and Terpene-4-ol have the potential to be used as naturally safe and efficient preservatives or active packaging to prevent OTA contamination.
Asunto(s)
Aspergillus , Monoterpenos Ciclohexánicos , Simulación del Acoplamiento Molecular , Ocratoxinas , Terpenos , Ocratoxinas/metabolismo , Ocratoxinas/biosíntesis , Aspergillus/metabolismo , Aspergillus/efectos de los fármacos , Terpenos/metabolismo , Aceite de Árbol de Té/farmacología , Aceite de Árbol de Té/química , Monoterpenos/farmacología , Monoterpenos/metabolismo , Antifúngicos/farmacología , Antifúngicos/química , Monoterpenos BicíclicosRESUMEN
(-)-Carvone, a ketone monoterpene, is the main component of essential oils from several medicinal plants and has been reported to have anti-arthriric, anticonvulsive, antidiabetic, anti-inflammatory, anticancer, and immunomodulatory effects. Therefore, this study aimed to investigate the spasmolytic activity of (-)-carvone in rodent models. The isolated virgin rat uterus was mounted in an organ bath apparatus, and the relaxing effect of ( -)-carvone and its mechanism of action were evaluated in tonic contractions induced by carbachol, KCl, PGF2α, or oxytocin. The animal model of primary dysmenorrhea was replicated with the injection of estradiol benzoate in female mice for three consecutive days, followed by intraperitoneal administration of oxytocin. Non-clinical acute toxicity evaluation was also performed. (-)-Carvone potency and effectiveness were larger in carbachol (pEC50 = 5.41 ± 0.14 and Emax = 92.63 ± 1.90% at 10-3 M) or oxytocin (pEC50 = 4.29 ± 0.17 and Emax = 86.69 ± 1.56% at 10-3 M) contractions. The effect of ( -)-carvone was altered in the presence of 4-aminopyridine, glibenclamide, L-NAME, or methylene blue. Mice pre-treated with (-)-carvone at a dose of 100 mg/kg showed a significant reduction in the number of writhing after oxytocin administration. No toxicity was observed after oral administration of 1 g/kg ( -)-carvone. Taken together, we showed that (-)-carvone reduced writhing by a spasmolytic effect, probably through the participation of KV and KATP channels and the nitric oxide pathway.
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Monoterpenos Ciclohexánicos , Monoterpenos , Oxitocina , Útero , Animales , Oxitocina/farmacología , Femenino , Monoterpenos Ciclohexánicos/farmacología , Ratones , Útero/efectos de los fármacos , Monoterpenos/farmacología , Contracción Uterina/efectos de los fármacos , Ratas , Ratas Wistar , Parasimpatolíticos/farmacología , Relajación Muscular/efectos de los fármacos , Carbacol/farmacologíaRESUMEN
α-Terpineol, an alcoholic monoterpene with lilac-like aroma, possesses diverse biological activities and has found applications in the food, pharmaceutical, cosmetic, and agricultural industries. Our previous studies indicated that gene PdTP1 was highly expressed in Penicillium digitatum DSM 62840 during the biotransformation of limonene to α-terpineol, while its actual biological functions are not fully understood. Here, PdTP1 was functionally characterized with bioinformatics analysis, subcellular localization, transcriptional activation activity, overexpression, and RNA interference (RNAi) silencing and RNA-seq analysis. Results showed that PdTP1 protein contained a GAL4-like Zn2Cys6 DNA-binding domain and a fungal_trans domain, was located in the nucleus and cell membrane and presented transcriptional activation effect, suggesting that PdTP1 encoded a Zn2Cys6 type transcription factor. Overexpression of PdTP1 in P. digitatum promoted limonene biotransformation and increased α-terpineol production, and opposite results were observed after the silencing of PdTP1. Moreover, transcription factor PdTP1 was found to affect the growth of P. digitatum and participate in ionic stress and oxidative stress responses. RNA-seq data revealed that altering the PdTP1 expression influenced the expression of some genes related to terpene metabolism or biosynthesis, fungal growth, and stress responses. In summary, PdTP1, which encoded a Zn2Cys6 transcription factor, played important roles in improving the production of α-terpineol from limonene and regulating fungal growth and environmental stress responses.
Asunto(s)
Biotransformación , Monoterpenos Ciclohexánicos , Proteínas Fúngicas , Limoneno , Penicillium , Factores de Transcripción , Penicillium/metabolismo , Penicillium/genética , Penicillium/crecimiento & desarrollo , Limoneno/metabolismo , Limoneno/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Monoterpenos Ciclohexánicos/metabolismo , Regulación Fúngica de la Expresión Génica , Terpenos/metabolismoRESUMEN
Genome wide analysis identified 14 OBPs in B. tabaci Asia II-1, of which six are new to science. Phylogenetic analysis traced their diversity and evolutionary lineage among Hemipteran insects. Comparative analysis reclassified the OBP gene families among B. tabaci cryptic species: Asia I, II-1, MEAM1, and MED. The 14 OBPs were clustered on four chromosomes of B. tabaci. RT-qPCR showed high expression of OBP3 and 8 across all body tissues and OBP10 in the abdomen. Molecular docking showed that OBP 3 and 10 had high affinity bonding with different candidate ligands, with binding energies ranging from -5.0 to -7.7 kcal/mol. Competitive fluorescence binding assays revealed that ß-caryophyllene and limonene had high binding affinities for OBP3 and 10, with their IC50 values ranging from 9.16 to 14 µmol·L-1 and KD values around 7 to 9 µmol·L-1. Behavioural assays revealed that ß-caryophyllene and carvacrol were attractants, ß-ocimene and limonene were repellents, and γ-terpinene and ß-ocimene were oviposition deterrents to B. tabaci. Functional validation by RNAi demonstrated that OBP3 and OBP10 modulated host recognition of B. tabaci. This study expands our understanding of the genomic landscape of OBPs in B. tabaci, offering scope for developing novel pest control strategies.
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Hemípteros , Proteínas de Insectos , Filogenia , Receptores Odorantes , Sesquiterpenos , Animales , Hemípteros/genética , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Receptores Odorantes/química , Proteínas de Insectos/genética , Proteínas de Insectos/química , Proteínas de Insectos/metabolismo , Sesquiterpenos/farmacología , Sesquiterpenos/metabolismo , Sesquiterpenos/química , Sesquiterpenos Policíclicos/farmacología , Sesquiterpenos Policíclicos/química , Cimenos/farmacología , Cimenos/química , Simulación del Acoplamiento Molecular , Monoterpenos/farmacología , Monoterpenos/metabolismo , Monoterpenos/química , Limoneno/farmacología , Limoneno/química , Limoneno/metabolismo , Monoterpenos Acíclicos/metabolismo , Monoterpenos Acíclicos/farmacología , Monoterpenos Acíclicos/química , Ciclohexenos/metabolismo , Ciclohexenos/farmacología , Ciclohexenos/química , Terpenos/metabolismo , Terpenos/química , Terpenos/farmacología , Genoma de los Insectos , Repelentes de Insectos/farmacología , Repelentes de Insectos/química , Genómica/métodos , Monoterpenos Ciclohexánicos , AlquenosRESUMEN
This study investigates the potential of the Threshold of Toxicological Concern (TTC) as an alternative to traditional animal testing in pesticide regulatory risk assessments. The TTC is a principle that establishes exposure threshold values for chemicals with certain structural features, below which there is no appreciable risk to human health. A case study was conducted with α-terpineol, an inert ingredient proposed to be used at low concentrations in pesticide products, to compare a conventional risk assessment using animal data with one using the TTC method. For the conventional risk assessment, animal data showed that there was no toxicity endpoint of concern, which resulted in a qualitative assessment and no risks of concern identified. For the risk assessment using the TTC method, a 5th percentile no-observed-effect level (NOEL) selected based on α-terpineol's Cramer classification was used as a point of departure (POD) for a quantitative risk assessment that resulted in no risks of concern identified. Therefore, the same conclusion was reached with both approaches and α-terpineol is considered safe for use in pesticide products at low concentrations. A comparative analysis was also performed to determine the applicability of the TTC method in calculating potential dietary risk from common pesticide use patterns for chemicals that fall within different Cramer classes. Results showed that use of the TTC method may be feasible for inert ingredient risk assessments when chemicals are used in a pesticide product at concentrations below 1%. This research underscores the TTC as a valuable and robust tool for assessing the potential hazards from inert ingredient use in pesticide formulations, considering factors such as chemical properties and the concentrations at which a chemical may be used in pesticide products. These findings contribute to the ongoing efforts by the United States Environmental Protection Agency (US EPA) to reduce animal testing in chemical safety assessments. The TTC method presents a viable alternative for risk evaluations of chemicals used at low concentrations, with anticipated low exposure, and with a predicted low toxicity potential.
Asunto(s)
Plaguicidas , Medición de Riesgo/métodos , Plaguicidas/toxicidad , Humanos , Animales , Nivel sin Efectos Adversos Observados , Pruebas de Toxicidad/métodos , Monoterpenos CiclohexánicosRESUMEN
In the present work, we describe the synthesis of new 1,3,4-thiadiazole derivatives from natural (R)-carvone in three steps including, dichloro-cyclopropanation, a condensation with thiosemicarbazide and then a 1,3-dipolar cycloaddition reaction with various nitrilimines. the targeted compounds were structurally identified by 1H & 13C NMR and HRMS analyses. The cytotoxic assay demonstrated that some synthesized novel compounds were potent on certain cancer cell lines. Molecular modeling studies were undertaken to rationalize the wet lab study results. Furthermore, molecular docking was performed to unveil the binding potential of the most active derivatives, 3a and 6c, to caspase-3 and COX-2. The stabilities of the protein-compound complexes obtained from the docking were evaluated using MD simulation. Furthermore, FMO and related parameters of the active compounds and their stereoisomers were examined through DFT studies. The docking study showed compound 6c had a higher binding potential than caspase-3. However, the binding strength of 6c was found to be less than that of the standard drug, doxorubicin, as it formed lower conventional hydrogen bonds. On the other hand, compound 3a had a higher binding potential to COX-2. However, the binding potential 3a was much lower than that of the standard COX-2 inhibitor, celecoxib. The MD simulation demonstrated that the caspase-3-6c complex was less stable than the caspase-3-doxorubicin complex. In contrast, the COX-2-3a complex was stable, and 3a was anticipated to remain inside the protein's binding pocket. The DFT study showed that 3a had higher chemical stability than 6c. The electron exchange capacity, chemical stability, and molecular orbital distributions of the stereoisomers of the active compounds were also found to be alike.
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Antineoplásicos , Monoterpenos Ciclohexánicos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Tiadiazoles , Humanos , Tiadiazoles/química , Tiadiazoles/farmacología , Tiadiazoles/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Estereoisomerismo , Monoterpenos Ciclohexánicos/química , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/química , Estructura Molecular , Ensayos de Selección de Medicamentos Antitumorales , Caspasa 3/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/química , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Teoría Funcional de la Densidad , Línea Celular TumoralRESUMEN
MAIN CONCLUSION: Mutation at A126 in lycopene-ß-cyclase of Crocus (CstLcyB2a) sterically hinders its binding of δ-carotene without affecting lycopene binding, thereby diverting metabolic flux towards ß-carotene and apocarotenoid biosynthesis. Crocus sativus, commonly known as saffron, has emerged as an important crop for research because of its ability to synthesize unique apocarotenoids such as crocin, picrocrocin and safranal. Metabolic engineering of the carotenoid pathway can prove a beneficial strategy for enhancing the quality of saffron and making it resilient to changing climatic conditions. Here, we demonstrate that introducing a novel mutation at A126 in stigma-specific lycopene-ß-cyclase of Crocus (CstLcyB2a) sterically hinders its binding of δ-carotene, but does not affect lycopene binding, thereby diverting metabolic flux towards ß-carotene formation. Thus, A126L-CstLcyB2a expression in lycopene-accumulating bacterial strains resulted in enhanced production of ß-carotene. Transient expression of A126L-CstLcyB2a in C. sativus stigmas enhanced biosynthesis of crocin. Its stable expression in Nicotiana tabacum enhanced ß-branch carotenoids and phyto-hormones such as abscisic acid (ABA) and gibberellic acids (GA's). N. tabacum transgenic lines showed better growth performance and photosynthetic parameters including maximum quantum efficiency (Fv/Fm) and light-saturated capacity of linear electron transport. Exogenous application of hormones and their inhibitors demonstrated that a higher ratio of GA4/ABA has positive effects on biomass of wild-type and transgenic plants. Thus, these findings provide a platform for the development of new-generation crops with improved productivity, quality and stress tolerance.
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Biomasa , Carotenoides , Crocus , Mutación , Estrés Fisiológico , Crocus/genética , Crocus/fisiología , Crocus/enzimología , Carotenoides/metabolismo , Estrés Fisiológico/genética , cis-trans-Isomerasas/genética , cis-trans-Isomerasas/metabolismo , Plantas Modificadas Genéticamente , beta Caroteno/metabolismo , Ácido Abscísico/metabolismo , Giberelinas/metabolismo , Ciclohexenos/metabolismo , Terpenos/metabolismo , Licopeno/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Monoterpenos Ciclohexánicos , Liasas Intramoleculares/genética , Liasas Intramoleculares/metabolismo , Nicotiana/genética , Nicotiana/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas , GlucósidosRESUMEN
Aim: This study explores the cytotoxic and apoptotic effects of novel thiazolidinone-1,2,3-triazole hybrids on HT-1080, A-549, and MDA-MB-231 cancer cell lines.Methods & results: The synthesized compounds underwent comprehensive characterization (NMR and HRMS) to confirm their structures and purity. Subsequent anticancer activity screening across diverse cancer cell lines revealed promising antitumor potential notably, compounds 6f and 6g. Mechanistic investigations unveiled that compound 6f triggers apoptosis through the caspase-3/7 pathway. In terms of in silico studies, the compound 6f was identified as a potent inhibitor of caspase-3 and caspase-7.Conclusion: The present study underscores the therapeutic potential of thiazolidinone-1,2,3-triazole hybrids against certain cancer cells. These findings highlight a promising avenue for the development of cancer treatment strategies utilizing these (R)-Carvone-based derivatives.
[Box: see text].
Asunto(s)
Antineoplásicos , Apoptosis , Ensayos de Selección de Medicamentos Antitumorales , Tiazolidinas , Triazoles , Humanos , Triazoles/química , Triazoles/farmacología , Triazoles/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Tiazolidinas/química , Tiazolidinas/farmacología , Tiazolidinas/síntesis química , Relación Estructura-Actividad , Proliferación Celular/efectos de los fármacos , Caspasa 3/metabolismo , Estructura Molecular , Caspasa 7/metabolismo , Simulación del Acoplamiento Molecular , Monoterpenos CiclohexánicosRESUMEN
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.
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Monoterpenos Acíclicos , Citrus , Monoterpenos Ciclohexánicos , Cromatografía de Gases y Espectrometría de Masas , Microextracción en Fase Sólida , Compuestos Orgánicos Volátiles , Cromatografía de Gases y Espectrometría de Masas/métodos , Citrus/química , Microextracción en Fase Sólida/métodos , Compuestos Orgánicos Volátiles/análisis , Compuestos Orgánicos Volátiles/química , Compuestos Orgánicos Volátiles/aislamiento & purificación , Monoterpenos Acíclicos/análisis , Monoterpenos Ciclohexánicos/análisis , Terpenos/análisis , Terpenos/química , Monoterpenos/análisis , Monoterpenos/aislamiento & purificación , Odorantes/análisis , Destilación/métodos , AcetatosRESUMEN
Neuropathic pain is a high-intensity pain that can be caused by compression, transection, injury, nerve infiltration and drug treatment of cancer. Furthermore, drug therapy has low clinical efficacy, many adverse effects and remission of painful symptoms. In this way, natural products derived from plants constitute a promising therapeutic alternative. Therefore, the aim of this study was to evaluate the antihyperalgesic effect of γ-terpinene (γ-TPN) e γ-terpinene in ß-cyclodextrin inclusion complexes (TPN/CD) on neuropathic pain induced by tumor cells. Complexation extended the effect time for another 5 h and daily treatment for six days with γ-TPN (50 mg/kg, p.o.) and γ-TPN/ß-CD (50 mg/kg, p.o.) significantly reduced (p < 0.001) the mechanical hyperalgesia induced by the administration of 2x106 sarcoma cells 180 in the around the sciatic nerve. In addition, the Grip and Rota-rod techniques demonstrated that there was no interference on the muscle strength and motor coordination of the animals, suggesting that the compound under study does not have central nervous system depressant effects at the doses used. Molecular docking studies demonstrate favorable binding energies between γ-TPN and ß-CD, and alpha-2 adrenergic, glutamatergic, opioid and cholinergic receptors. Thus, this study demonstrates the potential of terpinene complexation in controlling neuropathic pain induced by tumor cells.
Asunto(s)
Monoterpenos Ciclohexánicos , Hiperalgesia , Monoterpenos , Neuralgia , beta-Ciclodextrinas , Animales , beta-Ciclodextrinas/química , beta-Ciclodextrinas/administración & dosificación , Neuralgia/tratamiento farmacológico , Hiperalgesia/tratamiento farmacológico , Masculino , Monoterpenos/farmacología , Monoterpenos/química , Monoterpenos/administración & dosificación , Ratones , Analgésicos/farmacología , Analgésicos/química , Analgésicos/administración & dosificación , Modelos Animales de Enfermedad , Nervio Ciático/efectos de los fármacos , Nervio Ciático/lesiones , Línea Celular Tumoral , Simulación del Acoplamiento Molecular , Sarcoma 180/tratamiento farmacológico , Sarcoma 180/patologíaRESUMEN
Ajowan (Trachyspermum ammi L.) is considered a valuable spice and medicinal herb. In this study, the essential oil content and composition of the aerial parts of ajowan were investigated under different drying treatments (sun, shade, oven at 45 °C, oven at 65 °C, microwave, and freeze drying). Moreover, the phenolic content, flavonoid content, and antioxidant capacity of samples were also assessed. Fresh samples produced the highest essential oil content (1.05%), followed by those treated under sun (0.7%) and shade drying (0.95%). Based on gas chromatography-mass spectrometry (GC-MS), thirty compounds were determined in which thymol (34.84-83.1%), carvacrol (0.15-32.36%), p-cymene (0.09-13.66%), and γ-terpinene (3.12-22.58%) were the most abundant. Among the drying methods, freeze drying revealed the highest thymol content, followed by drying in a 45 °C oven. The highest TPC (total phenolic content) and TFC (total flavonoid content) were obtained in the fresh sample (38.23 mg TAE g-1 dry weight (DW)) and in the sample oven-dried at 45 °C (7.3 mg QE g-1 DW), respectively. Based on the HPLC results, caffeic acid (18.04-21.32 mg/100 gDW) and ferulic acid (13.102-19.436 mg/100 g DW) were the most abundant phenolic acids, while among flavonoids, rutin constituted the highest amount (10.26-19.88 mg/100 gDW). Overall, freeze drying was the most promising method of drying for preserving the phenolic (TPC) and flavonoid (TFC) compounds and oil components.
Asunto(s)
Antioxidantes , Flavonoides , Aceites Volátiles , Fenoles , Aceites Volátiles/química , Aceites Volátiles/análisis , Antioxidantes/química , Antioxidantes/análisis , Flavonoides/análisis , Flavonoides/química , Fenoles/análisis , Fenoles/química , Timol/análisis , Timol/química , Cimenos/química , Cimenos/análisis , Desecación/métodos , Cromatografía de Gases y Espectrometría de Masas , Extractos Vegetales/química , Monoterpenos CiclohexánicosRESUMEN
Dehydration is an effective method for the long-term storage and aroma retention of gonggan (Citrus sinensis Osb. 'Deqing Gonggan'), which is a Chinese variety of citrus, with unique and characteristic floral, fruity, and citrus flavors. However, the aroma profiles of gonggans prepared using oven- and freeze-drying, the most widely-used drying methods, remain unclear. In this study, a total of 911 volatile organic compounds (VOCs) were detected in dried gonggan. These were primarily composed of alcohols (7.69%), aldehydes (7.03%), esters (15.38%), ketones (7.58%), and terpenoids (23.19%). A total of 67 odorants contributed significantly to the overall aroma of dried gonggans, with the major odor qualities being detected as green, citrus, fruity, floral, and sweet. These were mainly attributed to the presence of aldehydes, esters, and terpenoids. Freeze-drying was more effective in maintaining the unique citrus and mandarin-like aromas attributed to compounds such as limonene, citrial, ß-myrcene, ß-pinene, and γ-terpinene. Moreover, (E,E)-2,4-decadienal had the highest relative odor activity value (rOAV) in freeze-dried gonggans, followed by (E)-2-nonenal, furaneol, (E, E)-2, 4-nonadienal, and E-2-undecenal. Oven-drying promoted the accumulation of terpenes such as octatriene, trans-ß-ocimene, cyclohexanone, copaene, and É-irone, imparting a soft aroma of flowers, fruits, and sweet. Increasing the temperature led to an increase in existing VOCs or the generation of new VOCs through phenylpropanoid, terpenoid, and fatty acid metabolism. The findings of this study offer insights into an optimized procedure for producing high-quality dried gonggans. These insights can be valuable for the fruit-drying industry, particularly for enhancing the quality of dried fruits.
Asunto(s)
Liofilización , Odorantes , Terpenos , Compuestos Orgánicos Volátiles , Compuestos Orgánicos Volátiles/análisis , Odorantes/análisis , Terpenos/análisis , Frutas/química , Citrus sinensis/química , Desecación/métodos , Aldehídos/análisis , Cromatografía de Gases y Espectrometría de Masas , Cetonas/análisis , Monoterpenos Bicíclicos/análisis , Ésteres/análisis , Alcadienos/análisis , Ciclohexenos/análisis , Manipulación de Alimentos/métodos , Monoterpenos Acíclicos , Monoterpenos Ciclohexánicos , Alquenos , SesquiterpenosRESUMEN
Dermatology and cosmetology currently prioritize healthy, youthful-looking skin. As a result, research is being conducted worldwide to uncover natural substances and carriers that allow for controlled release, which could aid in the battle against a variety of skin illnesses and slow the aging process. This study examined the biological and physicochemical features of novel hydrogels containing cannabidiol (CBD) and α-terpineol (TER). The hydrogels were obtained from ε-caprolactone (CL) and poly(ethylene glycol) (PEG) copolymers, diethylene glycol (DEG), poly(tetrahydrofuran) (PTHF), 1,6-diisocyanatohexane (HDI), and chitosan (CHT) components, whereas the biodegradable oligomers were synthesized using the enzyme ring-opening polymerization (e-ROP) method. The in vitro release rate of the active compounds from the hydrogels was characterized by mainly first-order kinetics, without a "burst release". The antimicrobial, anti-inflammatory, cytotoxic, antioxidant, and anti-aging qualities of the designed drug delivery systems (DDSs) were evaluated. The findings indicate that the hydrogel carriers that were developed have the ability to scavenge free radicals and impact the activity of antioxidant enzymes while avoiding any negative effects on keratinocytes and fibroblasts. Furthermore, they have anti-inflammatory qualities by impeding protein denaturation as well as the activity of proteinase and lipoxygenase. Additionally, their ability to reduce the multiplication of pathogenic bacteria and inhibit the activity of collagenase and elastase has been demonstrated. Thus, the developed hydrogel carriers may be effective systems for the controlled delivery of CBD, which may become a valuable tool for cosmetologists and dermatologists.
Asunto(s)
Cannabidiol , Hidrogeles , Piel , Hidrogeles/química , Hidrogeles/farmacología , Cannabidiol/farmacología , Cannabidiol/química , Piel/efectos de los fármacos , Piel/metabolismo , Humanos , Monoterpenos Ciclohexánicos/química , Monoterpenos Ciclohexánicos/farmacología , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/síntesis química , Regeneración/efectos de los fármacos , Polímeros/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Queratinocitos/efectos de los fármacos , Células HaCaT , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Antiinfecciosos/farmacología , Antiinfecciosos/químicaRESUMEN
Isoprenoid metabolism and its derivatives took part in photosynthesis, growth regulation, signal transduction, and plant defense to biotic and abiotic stresses. However, how aluminum (Al) stress affects the isoprenoid metabolism and whether isoprenoid metabolism plays a vital role in the Citrus plants in coping with Al stress remain unclear. In this study, we reported that Al-treatment-induced alternation in the volatilization rate of monoterpenes (α-pinene, ß-pinene, limonene, α-terpinene, γ-terpinene and 3-carene) and isoprene were different between Citrus sinensis (Al-tolerant) and C. grandis (Al-sensitive) leaves. The Al-induced decrease of CO2 assimilation, maximum quantum yield of primary PSII photochemistry (Fv/Fm), the lower contents of glucose and starch, and the lowered activities of enzymes involved in the mevalonic acid (MVA) pathway and 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway might account for the different volatilization rate of isoprenoids. Furthermore, the altered transcript levels of genes related to isoprenoid precursors and/or derivatives metabolism, such as geranyl diphosphate (GPP) synthase (GPPS) in GPP biosynthesis, geranylgeranyl diphosphate synthase (GGPPS), chlorophyll synthase (CHS) and GGPP reductase (GGPPR) in chlorophyll biosynthesis, limonene synthase (LS) and α-pinene synthase (APS) in limonene and α-pinene synthesis, respectively, might be responsible for the different contents of corresponding products in C. grandis and C. sinensis. Our data suggested that isoprenoid metabolism was involved in Al tolerance response in Citrus, and the alternation of some branches of isoprenoid metabolism could confer different Al-tolerance to Citrus species.