RESUMO
Parkinson's disease (PD) induced by environmental toxins involves a multifactorial cascade of harmful factors, thus motivating the search for therapeutic agents able to act on the greatest number of molecular targets. This study evaluated the efficacy of 50 mg/kg purified anacardic acids (AAs), isolated from cashew nut shell liquid, on multiple steps of oxidative stress and inflammation induced by rotenone in the substantia nigra (SN) and striatum. Adult mice were divided into four groups: Control, rotenone, AAs + rotenone, and AAs alone. Lipoperoxidation, nitric oxide (NO) levels, and reduced glutathione (GSH)/oxidized gluthatione (GSSG) ratio were evaluated. NF-kB-p65, pro-IL-1ß, cleaved IL-1ß, metalloproteinase-9, Tissue Inhibitory Factor-1 (TIMP-1), tyrosine hydroxylase (TH), and glial fibrillary acidic protein (GFAP) levels were assessed by Western blot. In silico studies were also made using the SwissADME web tool. Rotenone increased lipoperoxidation and NO production and reduced TH levels and GSH/GSSG ratio in both SN and striatum. It also enhanced NF-kB-p65, pro, and cleaved IL-1ß, MMP-9, GFAP levels compared to control and AAs groups. The AAs alone reduced pro-IL-1ß in the striatum while they augmented TIMP1 and reduced MMP-9 amounts in both regions. AAs reversed rotenone-induced effects on lipoperoxidation, NO production, and GSH/GSSG ratio, as well as increased TH and attenuated pro-IL-1ß and MMP-9 levels in both regions, NF-kB-p65 in the SN and GFAP in the striatum. Altogether, the in vivo and in silico analysis reinforced multiple and defined molecular targets of AAs, identifying that they are promising neuroprotective drug candidates for PD, acting against oxidative and inflammatory conditions induced by rotenone.
Assuntos
Ácidos Anacárdicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson Secundária/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Praguicidas/toxicidade , Ácidos Anacárdicos/química , Ácidos Anacárdicos/isolamento & purificação , Animais , Simulação por Computador , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Proteína Glial Fibrilar Ácida/genética , Glutationa/metabolismo , Dissulfeto de Glutationa/metabolismo , Humanos , Interleucina-1beta/genética , Peroxidação de Lipídeos/efeitos dos fármacos , Metaloproteinase 9 da Matriz/genética , Camundongos , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/etiologia , Doença de Parkinson/genética , Doença de Parkinson/patologia , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/genética , Doença de Parkinson Secundária/patologia , Inibidor Tecidual de Metaloproteinase-1/genética , Fator de Transcrição RelA/genética , Tirosina 3-Mono-Oxigenase/genéticaRESUMO
An extraction method based on a multivariate analytical approach was developed for enhancement of the phenolic compounds in cashew nut extracts. The different extractor solvents (acetone, water, ethanol, and methanol) and their binary, ternary, and quaternary combinations were evaluated using a simplex-centroid design and surface response methodology. The special cubic model exhibits no lack of fit and explains 89.2% of the variance. The total phenolic measurements by the Folin-Ciocalteu method revealed the highest values for ethanol (5.93â¯mg GAE g-1) and acetone-methanol-ethanol ternary mixture (5.92â¯mg GAE g-1) extracts. ESI (-)-Q/TOFMS analyses combined with PCA and HCA revealed the presence of fatty acids, phospholipids, and sugars in the ternary mixture cashew extract, while for the ethanol extract only phenolic compounds, such as anacardic acids and derivatives, were found. The proposed approach was adequate to reach the optimal extractor which ethanol, a low-toxicity solvent, enabled the selective extraction of a high content of phenolic compounds from cashew nuts.
Assuntos
Ácidos Anacárdicos/análise , Anacardium/química , Nozes/química , Extração em Fase Sólida/métodos , Acetona/química , Ácidos Anacárdicos/isolamento & purificação , Análise por Conglomerados , Etanol/química , Metanol/química , Análise Multivariada , Análise de Componente Principal , Solventes/química , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
In this work, we evaluated the ovicidal activity and the deleterious effects of cashew (Anacardium occidentale) nut shell oil and its fractions on the development of Musca domestica and Chrysomya megacephala, important vectors of several diseases. The insecticidal effects of this plant were also measured on the first and second instar larvae of Anticarsia gemmatalis and Spodoptera frugiperda, soy and maize pests, respectively. The fly eggs and the crop pest insect larvae were exposed to the cashew (Anacardium occidentale) nut shell liquid (CNSL) and its fractions: technical CNSL, anacardic acid, cardanol and cardol. The results show that the cardol fraction, for both species of flies, presented the lowest lethal concentration with LC50 of 80.4â mg/L for M. domestica and 90.2â mg/L for C. megacephala. For the mortality of the larvae of A. gemmatalis and S. frugiperda, the most effective fraction was anacardic acid with LC50 of 295.1â mg/L and 318.4â mg/L, respectively. In all species, the mortality rate of the commercial compounds (cypermethrin 600â mg/L and temephos 2â mg/L) was higher than that of the evaluated compounds. Despite this, the results obtained suggest their potential in field trials, once the fractions of A. occidentale presented high mortality at low lethal concentrations in laboratory conditions, with the possibility of integrated use in the control of disease vectors and agricultural pests, employing ecofriendly compounds.
Assuntos
Anacardium/química , Inseticidas/química , Óleos de Plantas/química , Ácidos Anacárdicos/química , Ácidos Anacárdicos/isolamento & purificação , Ácidos Anacárdicos/toxicidade , Anacardium/metabolismo , Animais , Dípteros/efeitos dos fármacos , Dípteros/crescimento & desenvolvimento , Moscas Domésticas/efeitos dos fármacos , Inseticidas/isolamento & purificação , Inseticidas/toxicidade , Larva/efeitos dos fármacos , Dose Letal Mediana , Nozes/química , Nozes/metabolismo , Óvulo/efeitos dos fármacos , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/toxicidade , Óleos de Plantas/metabolismo , Spodoptera/efeitos dos fármacos , Spodoptera/crescimento & desenvolvimentoRESUMO
Antianxiety drugs currently in use are associated with a number of serious side effects. Present study was designed to evaluate the efficacy of anacardic acids (AAs) isolated from cashew nut (Anacardium occidentale L.) shell liquid (CNSL) to treat anxiety as well as its role in oxidative stress in mice model. Anxiolytic effect of AA was evaluated using rota-rod and a set of behavioral tests in male Swiss albino mice at the doses of 10, 25, and 50 mg/kg. Flumazenil was used to evaluate the possible involvement of GABAergic system in the mechanism of action of AA. The effect of AA on oxidative stress in mice was evaluated by determining the concentration of malondialdehyde (MDA), reduced glutathione, and catalase (CAT) activity. The detection of DNA damage of the treated animals was performed using alkaline comet test in the hippocampus and frontal cortex of the animals. The results demonstrated that AA did not produce myorelaxant and sedative effects, nor did it cause a decrease in locomotor activity. The anxiolytic effect of AA was well-evident in all tests, especially at higher dose levels (25 and 50 mg/mg). Flumazenil reversed the anxiolytic effect of AA at all doses. In addition, AA reduced oxidative stress by decreasing the concentration of MDA and increasing the levels of reduced glutathione (GSH) and CAT activity. Statistical analysis by Pearson's correlation indicated a positive correlation between anxiolytic effect of AA to its antioxidant and lipid peroxidation inhibitory activity. Furthermore, increased CAT activity and GSH concentrations in the hippocampus and frontal cortex of mice was also complementary to the reduced genotoxic damage observed in the study. In comet assay, AA did not increase in DNA damage. In conclusion, the results supported that AA possesses GABAA receptor mediated anxiolytic activity with the lack of myorelaxation and genotoxicity. © 2018 IUBMB Life, 70(5):420-431, 2018.
Assuntos
Ácidos Anacárdicos/farmacologia , Anacardium/química , Ansiolíticos/farmacologia , Antioxidantes/farmacologia , Ansiedade/tratamento farmacológico , Ácidos Anacárdicos/química , Ácidos Anacárdicos/isolamento & purificação , Animais , Ansiolíticos/química , Ansiolíticos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Ansiedade/metabolismo , Ansiedade/fisiopatologia , Catalase/metabolismo , Diazepam/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Glutationa/metabolismo , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos ICR , Nozes/química , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Teste de Desempenho do Rota-RodRESUMO
BACKGROUND AND AIMS: Quorum sensing (QS) is a process of bacterial cell-cell communication that controls a large number of systems affecting pathogenicity. Interrupting this communication system can provide nonvirulent pathogenic bacteria. The aim of this study was to evaluate the anti-quorum sensing (anti-QS) potential of an anacardic acids mixture isolated from Amphipterygium adstringens, a medicinal plant known as "cuachalalate", to prevent the onset of bacterial infections as an alternate to antibiotics. METHODS: Initially we investigated the anti-QS activity of A. adstringens hexane extract (HE) by the inhibition of violacein production in Chromobacterium violaceum. From the active HE, an anacardic acid mixture (AAM) was obtained. The anti-quorum sensing activity of AAM was investigated by the rhamnolipid and pyocyanin production constraint as well as decrease of elastase activity, all being quorum sensing-controlled virulence factors expressed in the pathogenic bacteria Pseudomonas aeruginosa. RESULTS: HE induced a 91.6% of inhibition of the violecin production at 55 µg/mL concentration, whereas AAM showed 94% of inhibition at 166 µg/mL. In both cases, inhibition of violacein production did not affect the viability of the bacterium. AAM inhibited pyocyanin (86% at 200 µg/mL) and rhamnolipid (91% at 500 µg/mL) production in a dose/response form and decrease the elastase (75% at 500 µg/mL) activity in P. aeruginosa without affecting its development. CONCLUSIONS: Because an anacardic acids mixture isolated from A. adstringens demonstrated anti-QS, it could be further exploited for novel molecules to treat the emerging infections of antibiotic-resistant bacterial pathogens.
Assuntos
Ácidos Anacárdicos/farmacologia , Chromobacterium/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Fatores de Virulência/antagonistas & inibidores , Anacardiaceae/química , Ácidos Anacárdicos/isolamento & purificação , Animais , Antibacterianos/farmacologia , Chromobacterium/crescimento & desenvolvimento , Chromobacterium/patogenicidade , Farmacorresistência Bacteriana , Glicolipídeos/antagonistas & inibidores , Glicolipídeos/metabolismo , Indóis/antagonistas & inibidores , Indóis/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/patogenicidade , Piocianina/antagonistas & inibidores , Piocianina/metabolismo , Fatores de Virulência/metabolismoRESUMO
Amphipterygium adstringens (Schltdl.) Standl. (Anacardiaceae) is widely used in traditional Mexican medicine for the treatment of gastritis and ulcers. In this work, we studied the anti-Helicobacter pylori activity of its bark, this Gram-negative bacterium is considered the major etiological agent of chronic active gastritis and peptic ulcer disease, and it is linked to gastric carcinoma. From a bio-guided assay of the fractions obtained form a continuous Soxhlet extraction of the bark, we identified that petroleum ether fraction had significant antimicrobial activity against Helicobacter pylori. From this fraction, we isolated an anacardic acids mixture and three known triterpenes: masticadienonic acid; 3alpha-hydroxymasticadienonic acid; 3-epi-oleanolic; as well as the sterol beta-sitosterol. Only the anacardic acids mixture exhibits a potent dose-dependent antibacterial activity (MIC=10 microg/ml in broth cultures). It is enriched in saturated alkyl phenolic acids (C15:0, C16:0, C17:0 C19:0) which represents a novel source of these compounds with potent anti-Helicobacter pylori activity. The promising use of anacardic acids and Amphipterygium adstringens bark in the development of an integral treatment of Helicobacter pylori diseases is discussed.
Assuntos
Anacardiaceae/química , Ácidos Anacárdicos/farmacologia , Antibacterianos/farmacologia , Helicobacter pylori/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ácidos Anacárdicos/administração & dosagem , Ácidos Anacárdicos/isolamento & purificação , Antibacterianos/administração & dosagem , Antibacterianos/isolamento & purificação , Relação Dose-Resposta a Droga , Humanos , Hidroxibenzoatos/administração & dosagem , Hidroxibenzoatos/isolamento & purificação , Hidroxibenzoatos/farmacologia , Medicina Tradicional , México , Testes de Sensibilidade Microbiana , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Casca de Planta , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Sitosteroides/isolamento & purificação , Sitosteroides/farmacologia , Triterpenos/isolamento & purificação , Triterpenos/farmacologiaRESUMO
The bark of Amphipterygium adstringens is widely used in the traditional Mexican medicine for treating ailments such as gastric ulcers, gastritis and stomach cancer. The 6-nonadecyl salicylic acid (anacardic acid) was isolated from the bark of this species. In previous papers have been informed that the anacardic acids possess anti-tumour, antimicrobial, antiacne, antibacterial and many others medicinal properties. Now we describe cytotoxic and genotoxic effects of this compound and its methyl ester. The cytotoxic and genotoxic effects of 6-nonadecyl salicylic acid (6NDSA) and its methyl ester (ME6NDSA) on CD1 male mice were determined with micronucleus assay at 24, 48 and 72h after oral administration of doses of 0.75, 2.5, 5.0 and 10.0mg/kg. Peripheral blood samples were drawn from the caudal vein and analyzed by Giemsa-stained technique. The results obtained showed that the ratios of polychromatic erythrocytes (PCE) to normochromatic erythrocytes (NCE) in mice treated with 10mg/kg of 6NDSA were statistically lower after 24h compared with its negative control animals, and that after 72h, PCE/NCE ratios were reduced in animals treated with 6NDSA at all tested dose levels. The methyl ester ME6NDSA showed no such cytotoxic activity. Neither of the test compounds increased the frequency of micronucleated polychromatic erythrocytes from which it appears that administration of 6NDSA and ME6NDSA may not lead to chromosome damage at the evaluated doses.