RESUMO
Myristicin (MYR) mainly occurs in nutmeg and belongs to alkoxy-substituted allylbenzenes, a class of potentially toxic natural chemicals. RNA interaction with MYR metabolites in vitro and in vivo has been investigated in order to gain a better understanding of MYR toxicities. We detected two guanosine adducts (GA1 and GA2), two adenosine adducts (AA1 and AA2), and two cytosine adducts (CA1 and CA2) by LC-MS/MS analysis of total RNA extracts from cultured primary mouse hepatocytes and liver tissues of mice after exposure to MYR. An order of nucleoside adductions was found to be GAs > AAs > CAs, and the result of density functional theory calculations was in agreement with that detected by the LC-MS/MS-based approach. In vitro and in vivo studies have shown that MYR was oxidized by cytochrome P450 enzymes to 1'-hydroxyl and 3'-hydroxyl metabolites, which were then sulfated by sulfotransferases (SULTs) to form sulfate esters. The resulting sulfates would react with the nucleosides by SN1 and/or SN2 reactions, resulting in RNA adduction. The modification may alter the biochemical properties of RNA and disrupt RNA functions, perhaps partially contributing to the toxicities of MYR.
Assuntos
Ativação Metabólica , Derivados de Alilbenzenos , Sistema Enzimático do Citocromo P-450 , RNA , Sulfotransferases , Espectrometria de Massas em Tandem , Animais , Camundongos , Sulfotransferases/metabolismo , Sulfotransferases/genética , Sulfotransferases/química , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/química , Derivados de Alilbenzenos/química , Derivados de Alilbenzenos/metabolismo , RNA/metabolismo , RNA/química , Masculino , Hepatócitos/metabolismo , Dioxolanos/metabolismo , Dioxolanos/química , Dioxolanos/toxicidade , Fígado/metabolismo , Fígado/enzimologia , Dissulfetos/química , Dissulfetos/metabolismo , Myristica/química , Myristica/metabolismoRESUMO
The abnormal deposition of tau protein is one of the critical causes of tauopathies including Alzheimer's disease (AD). In recent years, there has been great interest in the use of essential oils and volatile compounds in aromatherapy for treating AD, since volatile compounds can directly reach the brain through intranasal administration. The volatile compounds α-asarone (ASA) and ß-caryophyllene (BCP) have revealed various important neuroprotective properties, useful in treating AD. In this study, the volatile compounds ASA and BCP were assessed for their effectiveness in preventing tau fibrillation, disassembly of pre-formed tau fibrils, and disaggregation of tau aggregates. SDS-PAGE and AFM analyses revealed that ASA and BCP inhibited tau fibrillation/aggregation and decreased the mean size of tau oligomers. Tau samples treated with ASA and BCP, showed a reduction in ThT and ANS fluorescence intensities, and a decrease in the ß-sheet content. Additionally, ASA and BCP disassembled the pre-formed tau fibrils to the granular and linear oligomeric intermediates. Treatment of neuroblastoma SH-SY5Y cells with tau samples treated with ASA and BCP, revealed protective effects as shown by reduced toxicity of the cells, due to the inhibition of tau fibrillation/aggregation. Overall, ASA and BCP appeared to be promising therapeutic candidates for AD.
Assuntos
Derivados de Alilbenzenos , Doença de Alzheimer , Anisóis , Sesquiterpenos Policíclicos , Proteínas tau , Proteínas tau/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Humanos , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/química , Derivados de Alilbenzenos/farmacologia , Derivados de Alilbenzenos/química , Anisóis/farmacologia , Anisóis/química , Linhagem Celular Tumoral , Agregados Proteicos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Sesquiterpenos/farmacologia , Sesquiterpenos/químicaRESUMO
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.
Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Matricaria , Óleos Voláteis , Óleos Voláteis/química , México , Matricaria/química , Sesquiterpenos/química , Sesquiterpenos/análise , Sesquiterpenos Monocíclicos/química , Derivados de Alilbenzenos/químicaAssuntos
Derivados de Alilbenzenos/toxicidade , Anisóis/toxicidade , Perfumes/toxicidade , Derivados de Alilbenzenos/química , Animais , Anisóis/química , Qualidade de Produtos para o Consumidor , Dano ao DNA/efeitos dos fármacos , Determinação de Ponto Final , Humanos , Isomerismo , Masculino , Perfumes/química , Ratos , Ratos Sprague-Dawley , Reprodução/efeitos dos fármacos , Medição de Risco , Testes de ToxicidadeRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Hyperglycemia (HG) and lipopolysaccharide (LPS) often promote superoxide accumulation, which may increase oxidative stress. Reducing superoxide production in hyperglycemia and the inflammatory condition is an emerging way to reduce protein and lipid oxidation and diabetes complication. AIM OF STUDY: To examine the effect of Agastache foeniculum essential oil (AFEO) and oil fraction (AFoil) on HG- and LPS-stimulated oxidative stress, the pathogenicity of AFEO and AFoil on oxidative stress was assessed. METHODS: The stimulatory effects of AFEO and AFoil on the activity and expression of NADH oxide (NOX), catalase (CAT), superoxide dismutase (SOD), and the expression of nuclear respiratory factor 2 (NRF2) and nuclear factor-kappa B (NF-kB) in the stimulated macrophage cell line, J774.A1, was studied. The interaction patterns of AFEO and AFoil components with NOX, SOD, CAT, NRF2, and NF-kB proteins were also deduced using molecular docking. RESULTS: Estragole was the main ingredient in AFEO (97%). Linolenic acid (32.10%), estragole (16.22%), palmitic acid (12.62%), linoleic acid (12.04%), and oleic acid (8.73%) were the major chemical components of the AFoil. NOX activation was stimulated in macrophage cells by HG and LPS. At 20 µg/mL, AFEO and AFoil decreased NOX activity while increased SOD and CAT activities in stimulated macrophages. AFoil with estragole and omega-3 fatty acids was better than AFEO with estragole in anti-hyperglycemic and anti-oxidative activity. According to molecular docking research, estragole, linoleic acid, and linolenic acid bind to different hydrophobic pockets of NOX, SOD, CAT, NFR2, and NF-kB using hydrogen bonds, van der Waals bonds, pi-alkyl, and pi-anion interactions, with different binding energies. CONCLUSION: AFEO and AFoil showed antioxidant and anti-diabetic activity. The mechanisms in lowering oxidative stress markers depended on down-regulating superoxide-producing enzymes and up-regulating superoxide-removing enzymes at gene and protein levels. The AFoil emulsion can be used to reduce the detrimental impacts of hyperglycemia and oxidative stress.
Assuntos
Agastache/química , Antioxidantes/farmacologia , Hipoglicemiantes/farmacologia , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Derivados de Alilbenzenos/química , Derivados de Alilbenzenos/farmacologia , Animais , Anisóis/química , Anisóis/farmacologia , Antioxidantes/química , Catalase/genética , Catalase/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose , Hipoglicemiantes/química , Ácido Linoleico/química , Ácido Linoleico/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Modelos Moleculares , Complexos Multienzimáticos/química , Complexos Multienzimáticos/metabolismo , NADH NADPH Oxirredutases/química , NADH NADPH Oxirredutases/metabolismo , Óleos Voláteis/química , Estresse Oxidativo , Óleos de Plantas/química , Conformação Proteica , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Ácido alfa-Linolênico/química , Ácido alfa-Linolênico/farmacologiaRESUMO
Laccase-based biocatalytic reactions have been tested with and without mediators and optimized in the oxidation of allylbenzene derivatives, such as methyl eugenol taken as a model substrate. The reaction primarily consisted in the hydroxylation of the propenyl side chain, either upon isomerization of the double bond or not. Two pathways were then observed; oxidation of both allylic alcohol intermediates could either lead to the corresponding α,ß-unsaturated carbonyl compound, or the corresponding benzaldehyde derivative by oxidative cleavage. Such a process constitutes a green equivalent of ozonolysis or other dangerous or waste-generating oxidation reactions. The conversion rate was sensitive to the substitution patterns of the benzenic ring and subsequent electronic effects.
Assuntos
Derivados de Alilbenzenos/química , Derivados de Alilbenzenos/metabolismo , Lacase/química , Lacase/metabolismo , Ozônio/metabolismo , Biocatálise , Eugenol/análogos & derivados , Eugenol/metabolismo , Concentração de Íons de Hidrogênio , Oxirredução , Ozônio/química , Especificidade por Substrato , Temperatura , Fatores de TempoRESUMO
Hedyosmum racemosum (Ruiz & Pav.) G. is a native species of Ecuador used in traditional medicine for treatment of rheumatism, bronchitis, cold, cough, asthma, bone pain, and stomach pain. In this study, fresh H. racemosum leaves of male and female specimens were collected and subjected to hydrodistillation for the extraction of the essential oil. The chemical composition of male and female essential oil was determined by gas chromatography-gas chromatography equipped with a flame ionization detector and coupled to a mass spectrometer using a non-polar and a polar chromatographic column. The antibacterial activity was assayed against five Gram-positive and two Gram-negative bacteria, and two dermatophytes fungi. The scavenging radical properties of the essential oil were evaluated by DPPH and ABTS assays. The chemical analysis allowed us to identify forty-three compounds that represent more than 98% of the total composition. In the non-polar and polar column, α-phellandrene was the principal constituent in male (28.24 and 25.90%) and female (26.47 and 23.90%) essential oil. Other main compounds were methyl chavicol, germacrene D, methyl eugenol, and α-pinene. Female essential oil presented a strong activity against Klebsiella pneumoniae (ATCC 9997) with an minimum inhibitory concentration (MIC) of 500 µg/mL and a scavenging capacity SC50 of 800 µg/mL.
Assuntos
Antibacterianos/química , Antioxidantes/química , Monoterpenos Cicloexânicos/química , Magnoliopsida/química , Óleos Voláteis/química , Derivados de Alilbenzenos/química , Derivados de Alilbenzenos/isolamento & purificação , Anisóis/química , Anisóis/isolamento & purificação , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Arthrodermataceae/efeitos dos fármacos , Arthrodermataceae/crescimento & desenvolvimento , Benzotiazóis/antagonistas & inibidores , Monoterpenos Bicíclicos/química , Monoterpenos Bicíclicos/isolamento & purificação , Compostos de Bifenilo/antagonistas & inibidores , Monoterpenos Cicloexânicos/isolamento & purificação , Equador , Eugenol/análogos & derivados , Eugenol/química , Eugenol/isolamento & purificação , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Humanos , Magnoliopsida/metabolismo , Masculino , Testes de Sensibilidade Microbiana , Picratos/antagonistas & inibidores , Folhas de Planta/química , Plantas Medicinais , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/isolamento & purificação , Fatores Sexuais , Ácidos Sulfônicos/antagonistas & inibidoresRESUMO
In the present study, we compared the antiepileptic effects of α-asarone derivatives to explore their structure-activity relationships using the PTZ-induced seizure model. Our research revealed that electron-donating methoxy groups in the 3,4,5-position on phenyl ring increased antiepileptic potency but the placement of other groups at different positions decreased activity. Besides, in allyl moiety, the optimal activity was reached with either an allyl or a 1-butenyl group in conjugation with the benzene ring. The compounds 5 and 19 exerted better neuroprotective effects against epilepsy in vitro (cell) and in vivo (mouse) models. This study provides valuable data for further exploration and application of these compounds as potential anti-seizure medicines.
Assuntos
Derivados de Alilbenzenos/química , Derivados de Alilbenzenos/uso terapêutico , Anisóis/química , Anisóis/uso terapêutico , Anticonvulsivantes/química , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Derivados de Alilbenzenos/síntese química , Animais , Anisóis/síntese química , Anticonvulsivantes/síntese química , Células Cultivadas , Modelos Animais de Doenças , Masculino , Camundongos , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/uso terapêutico , Ratos Sprague-Dawley , Relação Estrutura-AtividadeRESUMO
Flavonoid compounds are known for their antibacterial, anti-inflammatory, and anticancer properties. Therefore, they can influence membrane properties that interest us, modifying both their structure and functions. We used kaempferol (K) and myricetin (M) as representatives of this group. We investigated the influence of the abovementioned compounds on model cell membranes' properties (i.e., Langmuir monolayers and liposomes). The basic research methods used in these studies were the Langmuir method with Brewster angle microscopy and microelectrophoresis. The π-A isotherms were registered for the pure components and mixtures of these compounds with phosphatidylcholine (PC) in appropriate volume ratios. Using mathematical equations, we established that kaempferol, myricetin, and the lipids formed complexes at 1:1 ratios. We derived the parameters characterizing the formed complexes, i.e., the surfaces occupied by the complexes and the stability constants of the formed complexes. Using the microelectrophoretic method, we determined the dependence of the lipid membranes' surface charge density as a function of the pH (in the range of 2 to 10) of the electrolyte solution. The presented results indicate that the PC membrane's modification with kaempferol or myricetin affected changes in the surface charge density and isoelectric point values.
Assuntos
Derivados de Alilbenzenos/farmacologia , Dioxolanos/farmacologia , Eletroforese/métodos , Quempferóis/farmacologia , Membranas Artificiais , Microquímica/métodos , Fosfatidilcolinas/química , Lipossomas Unilamelares/química , Derivados de Alilbenzenos/química , Difusão , Dioxolanos/química , Concentração de Íons de Hidrogênio , Quempferóis/química , Microscopia de Polarização/métodos , Pressão , Refratometria , Eletricidade Estática , Propriedades de Superfície , Tensoativos , ViscosidadeRESUMO
One of the most common pathogens among yeasts is Candida albicans, which presents a serious health threat. The study aimed to check the antifungal properties of trans-anethole and eugenol with selected antifungal medicines (AMs) against C. albicans clinical isolates. The checkerboard method was used to tests of interactions between these compounds. Achieved results indicated that eugenol showed synergistic and additive activities with miconazole and econazole against investigated clinical isolates, respectively. Moreover, the combination - trans-anethole - miconazole also showed an additive effect against two clinical isolate. We tried to relate the results to changes in C. albicans cell sheaths under the influence of essential oils compounds (EOCs) performing the Fourier transform infrared spectra analysis to confirm the presence of particular chemical moieties in C. albicans cells. Nevertheless, no strong relationships was observed between synergistic and additive actions of used EOC-AMs combinations and chemical moieties in C. albicans cells.
Assuntos
Derivados de Alilbenzenos/farmacologia , Anisóis/farmacologia , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Eugenol/farmacologia , Derivados de Alilbenzenos/química , Anisóis/química , Antifúngicos/química , Candida albicans/isolamento & purificação , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Eugenol/química , Testes de Sensibilidade MicrobianaRESUMO
Alkenylbenzenes, including eugenol, methyleugenol, myristicin, safrole, and estragole, are potentially toxic phytochemicals, which are commonly found in foods. Occurrence data in foods depends on the quality of the analytical methodologies available. Here, we developed and compared modern reversed-phase high performance liquid chromatography (HPLC) and stacking-micellar electrokinetic chromatography (MEKC) methods for the determination of the above alkenylbenzenes in food flavouring ingredients. The analytical performance of HPLC was found better than the stacking-MEKC method. Compared to other HPLC methods found in the literature, our method was faster (total run time with conditioning of 15 min) and able to separate more alkenylbenzenes. In addition, the analytical methodology combining an optimized methanol extraction and proposed HPLC was then applied to actual food flavouring ingredients. This methodology should be applicable to actual food samples, and thus will be vital to future studies in the determination of alkenylbenzenes in food.
Assuntos
Aromatizantes/análise , Ingredientes de Alimentos/análise , Derivados de Alilbenzenos/química , Anisóis/química , Cromatografia Líquida de Alta Pressão , Cromatografia Capilar Eletrocinética Micelar , Cromatografia de Fase Reversa , Dioxolanos/química , Eugenol/análogos & derivados , Eugenol/química , Safrol/químicaRESUMO
Olfactory receptor (OR) genes in humans form a special class characterized by unusually high DNA sequence diversity, which should give rise to differences in perception and behavior. In the largest genome-wide association study to date based on olfactory testing, we investigated odor perception and naming with smell tasks performed by 9,122 Icelanders, with replication in a separate sample of 2,204 individuals. We discovered an association between a low-frequency missense variant in TAAR5 and reduced intensity rating of fish odor containing trimethylamine (p.Ser95Pro, pcombined = 5.6 × 10-15). We demonstrate that TAAR5 genotype affects aversion to fish odor, reflected by linguistic descriptions of the odor and pleasantness ratings. We also discovered common sequence variants in two canonical olfactory receptor loci that associate with increased intensity and naming of licorice odor (trans-anethole: lead variant p.Lys233Asn in OR6C70, pcombined = 8.8 × 10-16 and pcombined = 1.4 × 10-9) and enhanced naming of cinnamon (trans-cinnamaldehyde; intergenic variant rs317787-T, pcombined = 5.0 × 10-17). Together, our results show that TAAR5 genotype variation influences human odor responses and highlight that sequence diversity in canonical OR genes can lead to enhanced olfactory ability, in contrast to the view that greater tolerance for mutations in the human OR repertoire leads to diminished function.
Assuntos
Odorantes , Percepção Olfatória/genética , Neurônios Receptores Olfatórios/metabolismo , Receptores Acoplados a Proteínas G/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Derivados de Alilbenzenos/química , Anisóis/química , Cinnamomum zeylanicum/química , Feminino , Loci Gênicos , Estudo de Associação Genômica Ampla , Glycyrrhiza/química , Humanos , Islândia , Masculino , Metilaminas/química , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Polimorfismo de Nucleotídeo Único , Receptores Acoplados a Proteínas G/metabolismo , Olfato/fisiologia , Adulto JovemRESUMO
The organo-catalyzed enantioselective benzylation reaction of α-trifluoromethoxy indanones afforded α-benzyl-α-trifluoromethoxy indanones with a tetrasubstituted stereogenic carbon center in excellent yield with moderate enantioselectivity (up to 57% ee). Cinchona alkaloid-based chiral phase transfer catalysts were found to be effective for this transformation, and both enantiomers of α-benzyl-α-trifluoromethoxy indanones were accessed, depended on the use of cinchonidine and cinchonine-derived catalyst. The method was extended to the enantioselective allylation reaction of α-trifluoromethoxy indanones to give the allylation products in moderate yield with good enantioselectivity (up to 76% ee).