RESUMEN
The natural antimicrobial properties of essential oils (EOs) have contributed to the battle against multidrug-resistant microorganisms by providing new ways to develop more effective antibiotic agents. In this study, we investigated the chemical composition of Ocotea diospyrifolia essential oil (OdOE) and its antimicrobial properties combined with amikacin (AMK). Through gas chromatography-mass spectrometry (GCMS) analysis, the primary constituents of OdOE were identified as α-bisabolol (45.8 %), ß-bisabolene (9.4 %), γ-elemene (7.6 %), (Z)- ß-farnesene (5.2 %), spathulenol (3.5 %), (Z)-caryophyllene (3.3 %), and (E)-caryophyllene (3.1 %). In vitro assessments showed that the combined administration of OdOE and AMK exerted a synergistic antibacterial effect on the multidrug-resistant K. pneumoniae strain. This synergistic effect demonstrated bacteriostatic action. OdEO combined with amikacin showed protein extravasation within 2 h of treatment, leading to bacterial death, which was determined by a reduction in viable cell count. The effective concentrations showed hemocompatibility. In vivo assessments using Caenorhabditis elegans as a model showed the survival of 85 % of infected nematodes. Therefore, the combination OdEO combined with amikacin exhibited antimicrobial activity against a multidrug-resistant K. pneumoniae strain. Thus, OdOE is a promising agent that may be considered for development of antimicrobial treatment.
Asunto(s)
Amicacina , Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Sinergismo Farmacológico , Klebsiella pneumoniae , Pruebas de Sensibilidad Microbiana , Aceites Volátiles , Amicacina/farmacología , Aceites Volátiles/farmacología , Aceites Volátiles/química , Animales , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Antibacterianos/farmacología , Klebsiella pneumoniae/efectos de los fármacos , Cromatografía de Gases y Espectrometría de Masas , Caenorhabditis elegans/efectos de los fármacos , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Sesquiterpenos Monocíclicos/farmacología , Sesquiterpenos Policíclicos/farmacología , Sesquiterpenos Policíclicos/química , Sesquiterpenos/farmacologíaRESUMEN
α-Bisabolol (α-BIS) is a sesquiterpene alcohol present in chamomile essential oil [Chamomilla recutita (L.) Rauschert]. Despite its numerous pharmacological effects, its pharmacokinetics remain understudied. An analytical method capable of quantifying α-BIS in plasma is crucial to enable pharmacokinetic analysis. Presently, only one study has quantified it using mass spectrometry. Administering α-BIS requires a nanoemulsion for intravenous injection. This study aimed to develop and validate a bioanalytical method using high-performance liquid chromatography with an ultraviolet detector to quantify α-BIS in rat plasma. The method employed acetonitrile and ultrapure water (80:20, v/v) as the mobile phase, with a flow rate of 1 ml/min and concentrations ranging from 465 to 29.625 µg/ml. All US Food and Drug Administration-designated assays were successful, indicating the method's precision, accuracy, sensitivity and linearity in determining α-BIS in rat plasma. The developed nanoemulsion, assessed through dynamic light scattering analysis, the ensemble collection of particles and polydispersity index evaluation, proved safe and effective for intravenous administration. The pharmacokinetic parameters such as volume of distribution, clearance and half-life indicated that α-BIS tends to persist in the body. This study provides a foundation for further research to explore α-BIS's potential pharmaceutical applications in the future.
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Emulsiones , Sesquiterpenos Monocíclicos , Animales , Cromatografía Líquida de Alta Presión/métodos , Ratas , Emulsiones/química , Reproducibilidad de los Resultados , Sesquiterpenos Monocíclicos/farmacocinética , Sesquiterpenos Monocíclicos/sangre , Sesquiterpenos Monocíclicos/química , Masculino , Proyectos Piloto , Modelos Lineales , Límite de Detección , Sesquiterpenos/farmacocinética , Sesquiterpenos/sangre , Sesquiterpenos/química , Ratas Sprague-Dawley , Espectrofotometría Ultravioleta/métodosAsunto(s)
Dermatitis Alérgica por Contacto , Dermatosis Facial , Sesquiterpenos Monocíclicos , Crema para la Piel , Humanos , Dermatitis Alérgica por Contacto/etiología , Dermatitis Alérgica por Contacto/diagnóstico , Dermatosis Facial/inducido químicamente , Crema para la Piel/efectos adversos , Crema para la Piel/química , Sesquiterpenos Monocíclicos/efectos adversos , Femenino , Pruebas del Parche , Sesquiterpenos/efectos adversos , Persona de Mediana Edad , Compuestos Epoxi/efectos adversosRESUMEN
α-humulene, a sesquiterpene found in essential oils of various plant species, has garnered interest due to its potential therapeutic applications. This scoping review aims to consolidate α-humulene's evidence base, informing clinical translation, and guiding future research directions. A scoping review was conducted of EMBASE, MEDLINE, and PubMed databases up to 14th July 2023. All studies describing original research on α-humulene extraction, as well as pre-clinical and clinical research, were included for review. Three hundred and forty articles were analysed. α-humulene yields ranged from negligible to 60.90% across plant species. In vitro experiments demonstrated cytotoxicity against adenocarcinomas (such as colorectal, pulmonary, breast, prostatic, lung, and ovarian), with varying responses in other cell models. Mechanistic insights revealed its involvement in mitochondrial dysfunction, diminished intracellular glutathione levels, and the induction of oxidative stress. In rodent studies, oral administration of α-humulene at 50 mg/kg reduced inflammation markers in paw oedema and ovalbumin-induced airway inflammation. Intraperitoneal administration of α-humulene (50â-â200 mg/kg) exhibited cannabimimetic properties through cannabinoid 1 and adenosine A2a receptors. α-humulene also exhibited a multitude of properties with potential scope for therapeutic utilisation. However, there is a paucity of studies that have successfully translated this research into clinical populations with the associated disease. Potential barriers to clinical translation were identified, including yield variability, limited isolation studies, and challenges associated with terpene bioavailability. Consequently, rigorous pharmacokinetic studies and further mechanistic investigations are warranted to effectively uncover the potential of α-humulene.
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Sesquiterpenos Monocíclicos , Aceites Volátiles , Sesquiterpenos Monocíclicos/farmacología , Sesquiterpenos Monocíclicos/química , Humanos , Animales , Aceites Volátiles/farmacología , Aceites Volátiles/química , Sesquiterpenos/farmacología , Sesquiterpenos/aislamiento & purificación , Extractos Vegetales/farmacología , Extractos Vegetales/químicaRESUMEN
The present work aimed to investigate the effect of salinity in natural habitats in Egypt on the main secondary metabolites of Rosmarinus officinalis L. and Artemisia monosperma L. plants compared to plants grown at normal conditions. Plants grown under salinity were collected from Egyptian Western Coastal region habitats irrigated with underground water. Results showed that salinity increased the essential oil percentage of R. officinalis L. by 52.7% and A. monosperma L by 0.29% in addition to the total phenolics and flavonoids content in dry leaves compared to control plants. GC/MS analysis of rosemary essential oils revealed that salinity decreased the amount of some major oil monoterpenes component as verbenone, with a slight effect on 1,8 cineole and increased Camphor, endo- Boreneol, and linalool in addition to the appearance of new specific components such as Chrysanthenone monoterpene ketone and Caryophyllene sesquiterpene, while, in the case of Artemisia, the GC/MS showed that Artemisia ketone, Camphor, ß -phellandrene monoterpenes andα-Bisabolol sesquiterpenewere the major oil components; salinity decreased Camphor and ß -phellandrene content and increased artemisia ketone and α-Bisabolol oil content. About 11 new oil constituents were detected such as ( +)-2-Bornanone and Sesquisabinene hydrate. Mineral ions (N, K+, Ca+2, P, and Mg+2) uptake by R. officinalis and A. monosperma decreased in plants grown under salinity, while Na content increased compared to corresponding controls. Results demonstrated that both plants could tolerate the high salinity level in natural Western Coastal region soil which promoted more production of valuable secondary metabolites. The antimicrobial effect of R. officinalis L. and A. monosperma L. leaf methanolic extracts, results showed that R. officinalis extracts had an inhibitory response against all tested gram-positive and negative bacteria, in addition to the yeast (Candida albicans), whereas there was no any inhibitory effect concerning A. monosperma L extract on the tested species.
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Antiinfecciosos , Artemisia , Monoterpenos Ciclohexánicos , Sesquiterpenos Monocíclicos , Aceites Volátiles , Rosmarinus , Alcanfor/farmacología , Egipto , Aceites Volátiles/farmacología , Monoterpenos/farmacología , Hojas de la PlantaRESUMEN
The indiscriminate use of synthetic herbicides reduces its effectiveness. Bioherbicides produced with metabolites emerge as an alternative to managing weeds. We aimed to analyze the phytotoxic potential of the essential oil of Vanillosmopsis arborea (EOVA) and the α-bisabolol molecule, its main component. We evaluated the effects of EOVA and α-bisabolol at different concentrations on the germination, growth, antioxidant metabolism, and photosynthesis of different species. EOVA and α-bisabolol showed promising phytotoxic effects on the germination and initial growth of the weed Senna occidentalis, inhibiting the activity of the antioxidant enzymes and increasing lipid peroxidation. α-Bisabolol reduced the weed seedling growth by inducing oxidative stress, which suggests a greater role in postemergence. Moreover, in the weed postemergence, both EOVA and α-bisabolol caused damage in the shoots, reduced the chlorophyll content, and increased lipid peroxidation besides reducing photosynthesis in S. occidentalis. Overall, we suggest the promising action of α-bisabolol and EOVA as bioherbicides for weed control.
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Herbicidas , Control de Malezas , Antioxidantes , Sesquiterpenos Monocíclicos , Herbicidas/farmacologíaRESUMEN
The essential oils prepared by hydrodistillation of twenty-one brands of German chamomile (S1-S21) commercialized in Mexico were analyzed by GS-MS. Altogether, twenty-four different compounds were identified in the analyzed samples, varying from 77 to 100 % of the total composition. Multivariate analyses were applied to explore similarity/dissimilarity and correlation between all samples; the results revealed a strong correlation among samples S4, S5, and S7-S21 due to the presence of (Z)-en-yn-dicycloether [(Z)-tonghaosu], α-bisabolol, ß-farnesene, ß-eudesmol, and xanthoxylin. The samples S1-S3 and S6 were clustered separately. Samples S1, S3, and S6 were characterized by their higher content of bisabolol oxide A (38.78 %, 51.84 %, and 70.46 %, respectively) as most known chemotypes of German chamomile, but only S1 and S3 contained chamazulene. Finally, S2 differed from the others because of its high content of (E)-anethole (62.28 %), suggesting a case of adulteration or substitution of the crude drug employed for manufacturing the product.
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Cromatografía de Gases y Espectrometría de Masas , Matricaria , Aceites Volátiles , Aceites Volátiles/química , México , Matricaria/química , Sesquiterpenos/química , Sesquiterpenos/análisis , Sesquiterpenos Monocíclicos/química , Derivados de Alilbenceno/químicaRESUMEN
α-Bisabolol (αBIS), a plant-derived compound with anti-inflammatory properties, is potentially a therapeutic agent for Atopic dermatitis. However, its poor water solubility and photoinstability limit its topical application. Therefore, the present study, aimed to develop cationic polymeric nanocapsules of αBIS to improve its skin delivery, photostability, and therapeutic efficacy. The αBIS-loaded nanocapsules were prepared using the solvent displacement technique. A Box-Behnken (BB) design was employed to statistically optimize formulation variables and αBIS-loaded nanocapsules characterized by particle size, surface charge and encapsulation efficiency. The optimal formulation was selected, and the spherical shape of the nanocapsules was confirmed by scanning electron microscopy (SEM). Furthermore, hydrogel containing αBIS-loaded nanocapsules was prepared by thickening of nanocapsule suspension with Carbopol 934 and evaluated for rheology, in vitro drug release and skin permeation. Furthermore, a mice model of atopic dermatitis was used to evaluate the anti-inflammatory potential of the hydrogels. The optimal formulation displayed a spherical morphology under scanning electron microscopy (SEM) with an optimum particle size of 133.00 nm, polydispersity index (PDI) of 0.12, high EE% of 93 %, and improved optical stability of αBIS in the prepared nanocapsules compared to the free drug. The nano-based hydrogels demonstrated non-Newtonian pseudoplastic behavior and an increased αBIS in vitro release profile without causing skin irritation in rabbits. Drug retention within the dermis and epidermis layers significantly surpassed that of drug-free hydrogel. Moreover, in vivo histopathological studies and myeloperoxidase (MPO) enzyme activity, revealed that hydrogel containing bisabolol nanocapsules exhibited The best anti-inflammatory effect. The results showed that hydrogels containing bisabolol nanocapsules markedly alleviated dermatitis-related inflammation and reduced skin thickness in Balb/c mice. Our findings support nanocapsules as an effective drug delivery system to enhance αBIS stability, bioavailability, and therapeutic efficacy in AD treatment.
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Antiinflamatorios , Dermatitis Atópica , Liberación de Fármacos , Hidrogeles , Ratones Endogámicos BALB C , Sesquiterpenos Monocíclicos , Nanocápsulas , Animales , Hidrogeles/química , Hidrogeles/administración & dosificación , Nanocápsulas/química , Dermatitis Atópica/tratamiento farmacológico , Sesquiterpenos Monocíclicos/administración & dosificación , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Antiinflamatorios/farmacología , Absorción Cutánea/efectos de los fármacos , Tamaño de la Partícula , Modelos Animales de Enfermedad , Ratones , Administración Cutánea , Masculino , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología , Sesquiterpenos/administración & dosificación , Sesquiterpenos/química , Sesquiterpenos/farmacología , Sesquiterpenos/farmacocinética , FemeninoRESUMEN
Eight undescribed (1-8) and 46 known compounds (9-54) were isolated from the deep-sea-derived Aspergillus sp. MCCC 3A00392. Compounds 1-3 were three novel oxoindolo diterpenoids, 4-6 were three bisabolane sesquiterpenoids, while 7 and 8 were two monocyclic cyclopropanes. Their structures were established by exhaustive analyses of the HRESIMS, NMR, and theoretical calculations of the NMR data and ECD spectra. Compounds 10, 33, 38, and 39 were able to inhibit tumor necrosis factor (TNF)-induced necroptosis in murine L929 cell lines. Functional experiments verified that compounds 10 and 39 inhibited necroptosis by downregulating the phosphorylation of RIPK3 and MLKL. Moreover, compound 39 also reduced the phosphorylation of RIPK1. Compounds 10, 33, and 34 displayed potent inhibitory activities against RSL-3 induced ferroptosis with the EC50 value of 3.0 µM, 0.4 µM, and 0.1 µM, respectively. Compound 10 inhibited ferroptosis by the downregulation of HMOX1, while compounds 33 and 34 inhibited ferroptosis through regulation of NRF2/SLC7A11/GCLM axis. However, these compounds only showed weak effect in either the necroptosis or ferroptosis relative mouse disease models. Further studies of pharmacokinetics and pharmacodynamics might improve their in vivo bioactivities.
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Ferroptosis , Sesquiterpenos , Ratones , Animales , Necroptosis , Aspergillus/química , Sesquiterpenos/química , Sesquiterpenos MonocíclicosRESUMEN
Herein we report on the generation of hairy root lines of P. scaberrima able to produce hernandulcin (HE), a non-caloric sweetener with nutraceutical properties. From ten different lines analyzed, three synthesized up to 100â mg â L-1 HE under the batch culture conditions standardized in this investigation. Adding elicitors (salicylic acid, chitin, Glucanex, polyethylene glycol) and biosynthetic precursors (farnesol and (+)-epi-alpha-bisabolol) significantly altered HE accumulation. Chitin and Glucanex enhanced HE production from 130 to 160â mg â L-1 , whereas farnesol and (+)-epi-alpha-bisabolol from 165 to 200â mg â L-1 without dependence on biomass accumulation. Improved batch cultures containing liquid Murashige & Skoog medium (MS; pHâ 7), added with 4 % sucrose, 0.5â mg â L-1 naphthaleneacetic acid, 100â mg â L-1 Glucanex, 150â mg â L-1 chitin, 250â mg â L-1 farnesol, and 150â mg â L-1 (+)-epi-alpha-bisabolol at 25 °C (12â h light/12â h darkness), triggered HE accumulation to 250â mg â L-1 in 25â days. The efficiency of each recombinant line is discussed.
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Farnesol , Sesquiterpenos Monocíclicos , Sesquiterpenos , Edulcorantes , Edulcorantes/análisis , Farnesol/análisis , Suplementos Dietéticos , Quitina/análisis , Raíces de Plantas/químicaRESUMEN
BACKGROUND: The shortcomings of synthetic pesticides are becoming increasingly evident. In the pursuit of looking for alternative, environmentally friendly pesticides, the potential use of two naturally occurring sesquiterpenes, α-bisabolol and bisabolol oxide A, as bactericides or acaricides, was investigated against three gram-positive and three gram-negative bacteria, and the eggs and larvae of the cattle tick Hyalomma scupense, respectively. The primary targeted site of synthetic insecticides is acetylcholinesterase (AChE), so the inhibitory activity of both sesquiterpenes was evaluated. Then, molecular docking and molecular mechanics generalized Born surface area (MM-GBSA) studies were performed to gain insight into their binding mode in the AChE active site. RESULTS: Bisabolol oxide A showed good activity against Staphylococcus aureus, Escherichia coli, and Salmonella enteritidis with inhibition zones ranging from 16 to 34 mm and minimal inhibitory concentration (CIM) of 3.125 mg mL-1. Ovicidal and larvicidal assays revealed promising activity of α-bisabolol and bisabolol oxide A against H. scupense, with bisabolol oxide A being more effective against larval ticks with lethal concentration (LC50) value of 0.78%. Both compounds also displayed potent anti-AChE activity with inhibition concentration (IC50) values of 37.09 and 28.14 µg mL-1, respectively. Furthermore, α-bisabolol and bisabolol oxide A exhibited good and comparable docking scores (-7.289 and -7.139 Kcal mol-1, respectively) and were found to accommodate in the active-site gorge of AChE via hydrogen bonding and hydrophobic interactions. CONCLUSION: Bisabolol oxide A and, to a lesser degree, α-bisabolol are active against bacteria and ectoparasites and may represent an economical and sustainable alternative to toxic synthetic pesticides to control pathogens. © 2024 Society of Chemical Industry.
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Insecticidas , Sesquiterpenos Monocíclicos , Sesquiterpenos , Simulación del Acoplamiento Molecular , Acetilcolinesterasa/metabolismo , Sesquiterpenos/farmacología , Insecticidas/farmacología , ÓxidosRESUMEN
The sesquiterpene cyclase epi-isozizaene synthase (EIZS) from Streptomyces coelicolor catalyzes the metal-dependent conversion of farnesyl diphosphate (FPP) into the complex tricyclic product epi-isozizaene. This remarkable transformation is governed by an active site contour that serves as a template for catalysis, directing the conformations of multiple carbocation intermediates leading to the final product. Mutagenesis of residues defining the active site contour remolds its three-dimensional shape and reprograms the cyclization cascade to generate alternative cyclization products. In some cases, mutagenesis enables alternative chemistry to quench carbocation intermediates, e.g., through hydroxylation. Here, we combine structural and biochemical data from previously characterized EIZS mutants to design and prepare F95S-F198S EIZS, which converts EIZS into an α-bisabolol synthase with moderate fidelity (65% at 18 °C, 74% at 4 °C). We report the complete biochemical characterization of this double mutant as well as the 1.47 Å resolution X-ray crystal structure of its complex with three Mg2+ ions, inorganic pyrophosphate, and the benzyltriethylammonium cation, which partially mimics a carbocation intermediate. Most notably, the two mutations together create an active site contour that stabilizes the bisabolyl carbocation intermediate and positions a water molecule for the hydroxylation reaction. Structural comparison with a naturally occurring α-bisabolol synthase reveals common active site features that direct α-bisabolol generation. In showing that EIZS can be redesigned to generate a sesquiterpene alcohol product instead of a sesquiterpene hydrocarbon product, we have expanded the potential of EIZS as a platform for the development of designer cyclases that could be utilized in synthetic biology applications.
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Liasas de Carbono-Carbono , Sesquiterpenos , Sesquiterpenos/metabolismo , Sesquiterpenos MonocíclicosRESUMEN
With the increasing industrialization and urbanization, the ecological environment is suffering from severe deterioration in Liaohe coastal wetland, and petroleum spill is one of the pollution sources. Suaeda salsa (L.) Pall (S. salsa), one of the predominant plants in Liaohe coastal wetland, is facing the increasing degradation. Terpenes are a class of inherent compounds in plants, and play key role in maintain the growth of plants. However, the environmental stress on the terpene metabolism remained unclear in the plants. In the present study, the influence of petroleum spill on terpene metabolism in S. salsa was systematically investigated by analysis of concentrations, compositions and stable carbon isotope. Under the stress of petroleum spill, terpene concentrations showed the decreasing trend, indicating the inhibition effect of petroleum spill on terpene synthesis in S. salsa. The proportions of Sabinene and A-humulene showed the obviously increased with the influence of petroleum spill, implying that these congeners were more sensitive to petroleum spills. The significant changes in stable carbon isotope compositions were observed for Borneol, Dl-menthol, A-humulene and (-) -@-bisabolol, with the enrichment in heavier isotopes in residual fractions. This result indicated that the heavier 13C was preferentially fixed on terpene by S. salsa under the petroleum stress. The similar change trends along the incubation time was observed for A-humulene and (-) - trans caryophyllene, which might imply that A-humulene was one of the products of (-) - trans caryophyllene in S. salsa. Overall, the findings of present study verified the influence of petroleum spill on terpene metabolism in S. salsa, and were meaningful for protecting the plants in the petroleum-pollution wetlands.
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Chenopodiaceae , Petróleo , Sesquiterpenos Policíclicos , Humedales , Petróleo/toxicidad , Sesquiterpenos Monocíclicos , Isótopos de Carbono , CarbonoRESUMEN
This study explored the potential of poly-(lactic-co-glycolic) acid (PLGA) nanoparticles to enhance the effectiveness of anticancer treatments through combination therapy with phytol and α-bisabolol. The encapsulation efficiency of the nanoparticles was investigated, highlighting the role of ionic interactions between the drugs and the polymer. Characterization of PLGA-Phy+Bis nanoparticles was carried out using DLS with zeta potential and HR-TEM for size determination. Spectrophotometric measurements evaluated the encapsulation efficiency, loading efficiency, and in vitro drug release. FTIR analysis assessed the chemical interactions between PLGA and the drug actives, ensuring nanoparticle stability. GC-MS was employed to analyze the chemical composition of drug-loaded PLGA nanocarriers. Cytotoxicity was evaluated via the MTT assay, while Annexin V-FITC/PI staining and western blot analysis confirmed apoptotic cell death. Additionally, toxicity tests were performed on L-132 cells and in vivo zebrafish embryos. The study demonstrates high encapsulation efficiency of PLGA-Phy+Bis nanoparticles, which exhibit monodispersity and sizes of 189.3±5nm (DLS) and 268±54 nm (HR-TEM). Spectrophotometric analysis confirmed efficient drug encapsulation and release control. FTIR analysis revealed nanoparticle structural stability without chemical interactions. MTT assay results demonstrated the promising anticancer potential of all the three nanoparticle types (PLGA-Phy, PLGA-Bis, and PLGA-Phy+Bis) against lung cancer cells. Apoptosis was confirmed through Annexin V-FITC/PI staining and western blot analysis, which also revealed changes in Bax and Bcl-2 protein expression. Furthermore, the nanoparticles exhibited non-toxicity in L-132 cells and zebrafish embryo toxicity tests. PLGA-Phy+Bis nanoparticles exhibited efficient encapsulation, controlled release, and low toxicity. Apoptosis induction in A549 cells and non-toxicity in healthy cells highlight their clinical potential.
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Apoptosis , Sinergismo Farmacológico , Neoplasias Pulmonares , Sesquiterpenos Monocíclicos , Nanopartículas , Fitol , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Pez Cebra , Apoptosis/efectos de los fármacos , Animales , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Humanos , Nanopartículas/química , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Sesquiterpenos Monocíclicos/farmacología , Sesquiterpenos Monocíclicos/administración & dosificación , Fitol/administración & dosificación , Fitol/farmacología , Fitol/química , Fitol/toxicidad , Línea Celular Tumoral , Portadores de Fármacos/química , Células A549 , Liberación de Fármacos , Sesquiterpenos/farmacología , Sesquiterpenos/administración & dosificación , Sesquiterpenos/química , Sesquiterpenos/toxicidad , Supervivencia Celular/efectos de los fármacosRESUMEN
Mikania micrantha is a perennial liana of the genus Mikania of the Asteraceae family. It is a commonly used medicine in South America for treating fever, malaria, dysentery, snake bites, etc. Because of its strong adaptability and ability to inhibit the growth of its associated plants, Mikania micrantha is considered an invasive species in China and is known as a plant killer. Preliminary studies have shown that Mikania micrantha has an antipruritic effect, but the antipruritic active substance is not yet clear. In this study, a 4-aminopyridine-induced itching model in mice was used to determine the antipruritic effects of petroleum ether, ethyl acetate, ethanol extraction site, and Mikania micrantha volatile oil. GC-MS was used to analyze the components of the antipruritic fractions, combined with mice itch-causing models to study the antipruritic effects of ß-caryophyllene and humulene. The safety of ß-caryophyllene was preliminarily evaluated through the acute toxicity test of mice skin. The ethyl acetate and volatile oil of Mikania micrantha have apparent antipruritic effects. Humulene and ß-caryophyllene have a quantitative-effective relationship to inhibit itching in mice. The acute toxicity test of mouse skin showed that ß-caryophyllene has no acute toxicity. This study indicated that the main antipruritic active ingredients of Mikania micrantha are ß-caryophyllene and humulene.
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Acetatos , Mikania , Sesquiterpenos Monocíclicos , Aceites Volátiles , Sesquiterpenos Policíclicos , Animales , Ratones , Antipruriginosos/farmacología , Estructura Molecular , Aceites Volátiles/farmacología , PruritoRESUMEN
Alzheimer's disease (AD) is one of the major devastating neurodegenerative disorders associated with the gradual decline of an individual's memory, cognition, and ability to carry out day-to-day activities. In the present study, the neuroprotective ability of α-bisabolol ß-d-fucopyranoside (ABFP) was assessed via measurement of antioxidant parameters like lipid peroxidation, glutathione peroxidation, glutathione, protein carbonyl content assays, and caspase-3 activity estimation. Moreover, the acute toxicity of ABFP was estimated in the zebrafish larval model. The results showed that ABFP exhibits little to no toxicity at lower concentrations in the acute toxicity test. ABFP-pretreated and scopolamine-exposed fish exhibited more exploratory behavior in the behavior assay than scopolamine-only induced groups. Additionally, the results of antioxidant enzyme assays revealed reduced oxidative stress and damage in ABFP-treated fish, while enzyme activity experiments carried out with brain homogenate from ABFP-treated fish showed decreased acetylcholinesterase enzyme activity. Overall, it can be concluded that ABFP has the potential to be a promising agent for the treatment of AD in the future.
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Enfermedad de Alzheimer , Sesquiterpenos Monocíclicos , Pez Cebra , Animales , Pez Cebra/metabolismo , Escopolamina/efectos adversos , Antioxidantes/metabolismo , Acetilcolinesterasa/metabolismo , Carbonilación Proteica , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Estrés Oxidativo , Enfermedad de Alzheimer/inducido químicamente , Glutatión/metabolismoRESUMEN
BACKGROUND: Cannabis sativa L. (C. sativa) can efficiently synthesize of over 200 terpenes, including monoterpenes, sesquiterpenes and triterpenes that may contribute to the known biological activities of phytocannabinoids of relevance for the burgeoning access to medicinal cannabis formulations globally; however, to date have been uncharacterized. We assessed twelve predominant terpenes in C. sativa for neuroprotective and anti-aggregative properties in semi-differentiated PC12 neuronal cell line that is robust and validated as a cell model responsive to amyloid ß (Aß1-42) protein exposure and oxidative stress. METHODS: Cell viability was assessed biochemically using the MTT assay in the presence of myrcene, ß-caryophyllene, terpinolene, limonene, linalool, humulene, α-pinene, nerolidol, ß-pinene, terpineol, citronellol and friedelin (1-200 µM) for 24 hr. Sub-toxic threshold test concentrations of each terpene were then applied to cells, alone or with concomitant incubation with the lipid peroxidant tert-butyl hyrdroperoxide (t-BHP; 0-250 µM) or amyloid ß (Aß1-42; 0-1 µM) to assess neuroprotective effects. Direct effects of each terpene on Aß fibril formation and aggregation were also evaluated using the Thioflavin T (ThT) fluorometric kinetic assay and transmission electron microscopy (TEM) to visualize fibril and aggregate morphology. RESULTS: Terpenes were intrinsically benign to PC12 cells up to 50 µM, with higher concentrations of ß-caryophyllene, humulene and nerolidol inducing some loss of PC12 cell viability. No significant protective effects of terpenes were observed following t-BHP (0-200 µM) administration, with some enhanced toxicity instead demonstrated from both ß-caryophyllene and humulene treatment (each at 50 µM). α-pinene and ß-pinene demonstrated a significant neuroprotective effect against amyloid ß exposure. α-pinene, ß-pinene, terpineol, terpinolene and friedelin were associated with a variable inhibition of Aß1-42 fibril and aggregate density. CONCLUSIONS: The outcomes of this study underline a neuroprotective role of α-pinene and ß-pinene against Aß-mediated neurotoxicity associated with an inhibition of Aß1-42 fibrilization and density. This demonstrates the bioactive potential of selected terpenes for consideration in the development of medicinal cannabis formulations targeting neurodegenerative diseases.
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Monoterpenos Bicíclicos , Cannabis , Monoterpenos Ciclohexánicos , Alucinógenos , Lupanos , Marihuana Medicinal , Sesquiterpenos Monocíclicos , Fármacos Neuroprotectores , Sesquiterpenos Policíclicos , Sesquiterpenos , Animales , Ratas , Terpenos/farmacología , Terpenos/metabolismo , Péptidos beta-Amiloides/metabolismo , Neuroprotección , Marihuana Medicinal/farmacología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/químicaRESUMEN
Bauhinia ungulata is an antioxidant medicinal plant that has been manipuled in Brazil to lower glycemic index as well is for alternative treatment for diabetes. Therefore, the present hearch has aimed to investigates the antioxidant effects of the essential oil of Bauhinia ungulata L. (EOBU) collected in Amazon region better specified in Boa Vista, Roraima, Brazil, located in the Amazon region. Gas chromatography had been used to characterize the components, and antioxidant assays such as DPPH, TAC, reducing power, Fe2+ chelation, and total phenols had also been performed. The major constituents had molecularly anchored with the human catalase (CAT) enzyme, and maltol has showed as a positive control. Among the 25 revealed components, the main ones have been α-bisabolol (27.2 %), ß-Caryophyllene (12.5 %) and Epi-γ-eudesmol (13.6 %). The EOBU has comproved a TAC value of 618.79â mg of ascorbic acid equivalent, free radical scavenging capacity (DPPH) around 53.7 % and 65.27 %, Fe2+ chelation capacity of 161±6 and 126.7±39.6, for 0.1â mg.mL-1 and 0.5â mg.mL-1 , respectively. The power around the EOBU has appeared percentages equals to 28.66 %, 44.6 %, and 77.03 % in the concentrations tested. As well as, 96.5 % of total phenols. The compounds α-bisabolol (-5.7±0.4â Kcal.mol-1 ) and ß-caryophyllene (-6.1±0.5â Kcal.mol-1 ) have showed good interaction with CAT compared to Maltol (-4.4±0.4â Kcal.mol-1 ). The present work has demonstrated that EOBU functions as a potent antioxidant, capable of scavenging free radicals and reducing oxidative stress damage.
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Bauhinia , Sesquiterpenos Monocíclicos , Aceites Volátiles , Sesquiterpenos Policíclicos , Humanos , Antioxidantes/farmacología , Antioxidantes/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Fenoles/química , Extractos Vegetales/químicaRESUMEN
Two pairs of new bisabolane-type sesquiterpenoids, (+)-aspersydowin A (7S) [(+)-1], (-)-aspersydowin A (7R) [(-)-1], (+)-aspersydowin B (7S,11S) [(+)-2], (-)-aspersydowin B (7R,11R) [(-)-2], along with six known compounds (1-8) were isolated from the fungus Aspergillus sydowii. Compounds 1 and 2 are enantiomers resolved by the Chiralpak IC, using a hexane- propan-2-ol mobile phase. The structure of 1 and 2 with absolute configuration were assigned tentatively by 1D (1 H, 13 C, and DEPT) & 2D (HSQC, 1 H-1 H COSY, HMBC, and NOESY) NMR data analyses and ECD calculations. Compounds 1-8 were screened for the biological activities inâ vitro. The results showed that compounds 3, 4 and 8 exhibited immunosuppressive activities with IC50 values of 10.9, 17.6 and 13.4â µM, respectively.
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Aspergillus , Sesquiterpenos , Sesquiterpenos Monocíclicos , Estructura Molecular , Aspergillus/química , Sesquiterpenos/químicaRESUMEN
The class I sesquiterpene cyclase epi-isozizaene synthase from Streptomyces coelicolor (EIZS) catalyzes the transformation of linear farnesyl diphosphate (FPP) into the tricyclic hydrocarbon epi-isozizaene in the biosynthesis of albaflavenone antibiotics. The active site cavity of EIZS is largely framed by four aromatic residues - F95, F96, F198, and W203 - that form a product-shaped contour, serving as a template to chaperone conformations of the flexible substrate and multiple carbocation intermediates leading to epi-isozizaene. Remolding the active site contour by mutagenesis can redirect the cyclization cascade away from epi-isozizaene biosynthesis to generate alternative sesquiterpene products. Here, we present the biochemical and structural characterization of four EIZS mutants in which aromatic residues have been substituted with polar residues (F95S, F96H, F198S, and F198T) to generate alternative cyclization products. Most notably, F95S EIZS generates a mixture of monocyclic sesquiterpene precursors of bisabolane, a D2 diesel fuel substitute. X-ray crystal structures of the characterized mutants reveal subtle changes in the active site contour showing how each aromatic residue influences the chemistry of a different carbocation intermediate in the cyclization cascade. We advance that EIZS may serve as a robust platform for the development of designer cyclases for the generation of high-value sesquiterpene products ranging from pharmaceuticals to biofuels in synthetic biology approaches.