RESUMO
Polyphenols are the main active components in Vitis amurensis Rupr. wine, which show good protective effects on the nervous system, but their compositions in Vitis amurensis Rupr. wine and the molecular mechanism underlying their neuroprotection remains unclear. The purpose of this study is to investigate the potential mechanism of the neuroprotective effect of Vitis amurensis Rupr. wine polyphenols on the basis of the specific composition of polyphenols in Vitis amurensis Rupr. wine. In this study, 40 phenolic compounds which include 15 anthocyanins, 10 flavonoids, 10 phenolic acids, 3 proanthocyanidins and 2 resveratrols were identified by UPLC Q-Exactive Orbitrap MS. Furthermore, An UPLC-QqQ/MS method was established to simultaneously determine the phenolic compounds in Vitis amurensis Rupr. Wine, and analyze the content differences of phenolic compounds between Vitis amurensis Rupr. and Vitis vinifera wine. Finally, network pharmacology was employed for the first time to predict the possible pharmacological mechanisms of Vitis amurensis wine polyphenols against nervous damage. Multivariate network analysis indicated that quercetin, (-)-epigallocatechin and various anthocyanins were found as prominent compounds for the treatment of nervous system diseases. Vitis amurensis Rupr. wine polyphenols mainly acted on these key targets, including AKT1, EGFR, ESR1, and SRC, and further regulate the PI3K-AKT and Rap1 signaling pathway for treating nervous system diseases. Our findings suggested that polyphenols in Vitis amurensis Rupr. wine possess neuroprotective effect through multicomponent, multitarget, and multichannel. PRACTICAL APPLICATIONS: Studies have revealed that Vitis amurensis Rupr. has higher levels of phenolic compounds than Vitis vinifera wine. However, due to the few and limited study of Vitis amurensis Rupr., their compositions in Vitis amurensis Rupr. wine and the molecular mechanism underlying their neuroprotection remains unclear. This research uses a holistic network pharmacology strategy to investigate the potential targets and pharmacological mechanisms of Vitis amurensis Rupr. wine polyphenols against nervous damage. To some things up, The finding elucidates the relationships between signaling pathways, targets, and compounds in Vitis amurensis Rupr. wine polyphenols, which may provide guidance and foundations for further application of medicinal food.
Assuntos
Fármacos Neuroprotetores , Proantocianidinas , Vitis , Vinho , Antocianinas/análise , Cromatografia Líquida , Receptores ErbB/análise , Flavonoides/análise , Flavonoides/farmacologia , Farmacologia em Rede , Fármacos Neuroprotetores/análise , Fármacos Neuroprotetores/farmacologia , Fenóis/análise , Fosfatidilinositol 3-Quinases , Polifenóis/análise , Polifenóis/farmacologia , Proantocianidinas/análise , Proteínas Proto-Oncogênicas c-akt , Quercetina , Espectrometria de Massas em Tandem , Vinho/análiseRESUMO
Y. schidigera contains a number of unusual polyphenols, derivatives of resveratrol and naringenin, called spiro-flavostilbenoids, which have potent in vitro anti-inflammatory, antioxidant, and moderate cholinesterase inhibitory activities. To date, these compounds have not been tested in vivo for the treatment of neurodegenerative diseases. The aim of the present study was to evaluate the effects of both single spiro-flavostilbenoids (yuccaol B and gloriosaol A) and phenolic fractions derived from Y. schidigera bark on scopolamine-induced anxiety and memory process deterioration using a Danio rerio model. Detailed phytochemical analysis of the studied fractions was carried out using different chromatographic techniques and Nuclear Magnetic Resonance (NMR). The novel tank diving test was used as a method to measure zebrafish anxiety, whereas spatial working memory function was assessed in Y-maze. In addition, acetylcholinesterase/butyrylcholinesterase (AChE/BChE) and 15-lipooxygenase (15-LOX) inhibition tests were performed in vitro. All pure compounds and fractions under study exerted anxiolytic and procognitive action. Moreover, strong anti-oxidant capacity was observed, whereas weak inhibition towards cholinesterases was found. Thus, we may conclude that the observed behavioral effects are complex and result rather from inhibition of oxidative stress processes and influence on cholinergic muscarinic receptors (both 15-LOX and scopolamine assays) than effects on cholinesterases. Y. schidigera is a source of substances with desirable properties in the prevention and treatment of neurodegenerative diseases.
Assuntos
Fármacos Neuroprotetores , Yucca , Acetilcolinesterase , Animais , Antioxidantes/análise , Antioxidantes/farmacologia , Butirilcolinesterase , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Fármacos Neuroprotetores/análise , Fármacos Neuroprotetores/farmacologia , Fenóis/química , Casca de Planta/química , Extratos Vegetais/química , Escopolamina/efeitos adversos , Escopolamina/análise , Yucca/química , Peixe-ZebraRESUMO
Avocado (Persea americana) is a widely consumed fruit and a rich source of nutrients and phytochemicals. Its industrial processing generates peels and seeds which represent 30% of the fruit. Environmental issues related to these wastes are rapidly increasing and likely to double, according to expected avocado production. Therefore, this work aimed to evaluate the potential of hexane and ethanolic peel (PEL-H, PEL-ET) and seed (SED-H, SED-ET) extracts from avocado as sources of neuroprotective compounds. Minerals, total phenol (TPC), total flavonoid (TF), and lipid contents were determined by absorption spectroscopy and gas chromatography. In addition, phytochemicals were putatively identified by paper spray mass spectrometry (PSMS). The extracts were good sources of Ca, Mg, Fe, Zn, ω-6 linoleic acid, and flavonoids. Moreover, fifty-five metabolites were detected in the extracts, consisting mainly of phenolic acids, flavonoids, and alkaloids. The in vitro antioxidant capacity (FRAP and DPPH), acetylcholinesterase inhibition, and in vivo neuroprotective capacity were evaluated. PEL-ET was the best acetylcholinesterase inhibitor, with no significant difference (p > 0.05) compared to the control eserine, and it showed neither preventive nor regenerative effect in the neuroprotection assay. SED-ET demonstrated a significant protective effect compared to the control, suggesting neuroprotection against rotenone-induced neurological damage.
Assuntos
Fármacos Neuroprotetores , Persea , Acetilcolinesterase , Antioxidantes/química , Inibidores da Colinesterase/análise , Inibidores da Colinesterase/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Fármacos Neuroprotetores/análise , Fármacos Neuroprotetores/farmacologia , Persea/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
Alzheimer's disease (AD) is a progressive, neurodegenerative disorder that currently has reached epidemic proportions among elderly populations around the world. In China, available traditional Chinese medicines (TCMs) that organically combine functional foods with medicinal values are named "Medicine Food Homology (MFH)". In this review, we focused on MFH varieties for their traditional functional features, substance bases, clinical uses, and mechanisms of action (MOAs) for AD prevention and treatment. We consider the antiAD active constituents from MFH species, their effects on in vitro/in vivo AD models, and their drug targets and signal pathways by summing up the literature via a systematic electronic search (SciFinder, PubMed, and Web of Science). In this paper, several MFH plant sources are discussed in detail from in vitro/in vivo models and methods, to MOAs. We found that most of the MFH varieties exert neuroprotective effects and ameliorate cognitive impairments by inhibiting neuropathological signs (Aß-induced toxicity, amyloid precursor protein, and phosphorylated Tau immunoreactivity), including anti-inflammation, antioxidative stress, antiautophagy, and antiapoptosis, etc. Indeed, some MFH substances and their related phytochemicals have a broad spectrum of activities, so they are superior to simple single-target drugs in treating chronic diseases. This review can provide significant guidance for people's healthy lifestyles and drug development for AD prevention and treatment.
Assuntos
Doença de Alzheimer/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Alimento Funcional , Fármacos Neuroprotetores/uso terapêutico , Plantas Medicinais , Doença de Alzheimer/prevenção & controle , Animais , Alimento Funcional/análise , Humanos , Fármacos Neuroprotetores/análise , Extratos Vegetais/análise , Extratos Vegetais/uso terapêutico , Plantas Medicinais/químicaRESUMO
Huang-Lian-Jie-Du Decoction (HLJDD), a well-known traditional Chinese formulation, has been proved to exert neuroprotective effects, however, the bioactive components in HLJDD still remain to be elucidated. In the present study, a rapid and effective method involving live cell biospecific extraction and HPLC-Q-Orbitrap HRMS/MS was utilized to rapidly screen and identify the neuroprotective compounds from the HLJDD crude extract directly. Firstly, sixteen principal components in HLJDD crude extract were identified by HPLC-Q-Orbitrap HRMS/MS analysis. After co-incubation with PC12 cells, which have been validated as the key target cells for neurodegenerative diseases, seven compounds of them were demonstrated to exhibit binding affinity to the target cells. Furthermore, three representative compounds named baicalin, wogonoside, and berberine were subsequently verified to exert cytoprotective effects on PC12 cells injured by hydrogen peroxide via inhibiting oxidative stress and cell apoptosis, indicating that these screened compounds may possess a potential for the treatment of neurodegenerative diseases and were responsible, in part at least, for the neuroprotective beneficial effects of HLJDD. Taken together, our study provides evidence that live cell biospecific extraction coupled with LC-HRMS/MS technique is an efficient method for rapid screening potential bioactive components in traditional Chinese medicines.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Técnicas Citológicas/métodos , Medicamentos de Ervas Chinesas , Fármacos Neuroprotetores , Animais , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/farmacologia , Fármacos Neuroprotetores/análise , Fármacos Neuroprotetores/farmacologia , Células PC12 , Ratos , Espectrometria de Massas em TandemRESUMO
An anthocyanin-rich extract was obtained from Nitraria tangutorum Bobr. fruit, namely ANF, and its composition, antioxidant and neuroprotective effects were studied. Nine anthocyanins were identified from the ANF using UPLC-Triple-TOF/MS analysis, and cyanidin-3-[2''-(6'''-coumaroyl)-glucosyl]-glucoside (C3G) is the most abundant anthocyanin (87.06%). ANF exhibited high ferric reducing antioxidant power (FRAP) and ABTS radical scavenging activity. The online HPLC-DPPH screening revealed that C3G contributed the highest antioxidant capacity. ANF showed potential neuroprotective effects by relieving d-Galactose-induced memory deficits, reducing overexpression of receptor for advanced glycation end products (RAGE) and amyloid-beta42 (Aß42) in the hippocampus of rats. Besides, ANF could inhibit oxidative stress by reducing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in the hippocampus, while elevating amounts of total superoxide dismutase (T-SOD) and glutathione (GSH) in the serum of rats. Thus, ANF has great potential in the development of food and health products related to antioxidant and neuroprotective effects.
Assuntos
Antocianinas/análise , Antioxidantes/química , Cromatografia Líquida de Alta Pressão , Magnoliopsida/química , Fármacos Neuroprotetores/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Antocianinas/química , Antocianinas/isolamento & purificação , Antocianinas/farmacologia , Feminino , Frutas/química , Frutas/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Magnoliopsida/metabolismo , Malondialdeído/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Superóxido Dismutase/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Buyang Huanwu Decoction (BHD) is a multi-herbal composition commonly prescribed in the treatment of cerebrovascular diseases such as stroke. Although studies have been conducted at the cellular (in vitro), animal and human (in vivo) level, there was no detailed analysis on how the composition and proportion of BHD is modified according to target diseases. AIM OF STUDY: The purpose of this study is to investigate the composition and proportion of each herb in BHD to summarize how the original BHD was modified according to the target disease. MATERIALS AND METHODS: Electronic literature searches were performed in three databases, collecting sixty-eight studies for the final analysis. The studies were divided into three types: cell studies, animal experiments and clinical trial. In the analysis, the decoction formula including the composition and the weight proportion of the herbs in BHD used in the studies and the target diseases were examined. RESULTS: The result showed that in cell studies, the targets were mostly cell differentiation, cell injury and immune activation. In animal studies, cerebrovascular diseases such as cerebral ischemia were the most identified target diseases followed by nervous system and cardiovascular diseases. While the proportions of the herbs in BHD used in these studies were in general similar to the original formula, some studies reduced the amount of Astragali Radix to half of the original amount. Modified BHDs were used in four studies for cerebrovascular and peripheral nerve diseases. However, no significant correlation has been observed between the target diseases and the change of the proportion of the herbs in BHD. CONCLUSIONS: The most commonly used formula was the original composition of BHD, and modified BHDs were reported to be used to treat cerebrovascular and nervous diseases. Further studies about the effects of BHD by composition and proportion of herbs are needed in the future.
Assuntos
Fármacos Cardiovasculares/análise , Fármacos Cardiovasculares/uso terapêutico , Transtornos Cerebrovasculares/tratamento farmacológico , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/uso terapêutico , Cardiopatias/tratamento farmacológico , Fármacos Neuroprotetores/análise , Fármacos Neuroprotetores/uso terapêutico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Animais , Transtornos Cerebrovasculares/metabolismo , Transtornos Cerebrovasculares/patologia , Composição de Medicamentos , Cardiopatias/metabolismo , Cardiopatias/patologia , Humanos , Doenças do Sistema Nervoso Periférico/metabolismo , Doenças do Sistema Nervoso Periférico/patologiaRESUMO
Parkinson's disease (PD) patients have higher rates of melanoma and vice versa, observations suggesting that the two conditions may share common pathogenic pathways. ß-Catenin is a transcriptional cofactor that, when concentrated in the nucleus, upregulates the expression of canonical Wnt target genes, such as Nurr1, many of which are important for neuronal survival. ß-Catenin-mediated activity is decreased in sporadic PD as well as in leucine-rich repeat kinase 2 (LRRK2) and ß-glucosidase (GBA) mutation cellular models of PD, which is the most common genetic cause of and risk for PD, respectively. In addition, ß-catenin expression is significantly decreased in more aggressive and metastatic melanoma. Multiple observational studies have shown smokers to have significantly lower rates of PD as well as melanoma implying that tobacco may contain one or more elements that protect against both conditions. In support, smoker's brains have significantly reduced levels of α-synuclein, a pathological intracellular protein found in PD brain and melanoma cells. Tobacco contains very high lithium levels compared to other plants. Lithium has a broad array of neuroprotective actions, including enhancing autophagy and reducing intracellular α-synuclein levels, and is effective in both neurotoxin and transgenic preclinical PD models. One of lithium's neuroprotective actions is enhancement of ß-catenin-mediated activity leading to increased Nurr1 expression through its ability to inhibit glycogen synthase kinase-3 ß (GSK-3ß). Lithium also has anti-proliferative effects on melanoma cells and the clinical use of lithium is associated with a reduced incidence of melanoma as well as reduced melanoma-associated mortality. This is the first known report hypothesizing that inhaled lithium from smoking may account for the associated reduced rates of both PD and melanoma and that this protection may be mediated, in part, through lithium-induced GSK-3ß inhibition and consequent enhanced ß-catenin-mediated activity. This hypothesis could be directly tested in clinical trials assessing lithium therapy's ability to affect ß-catenin-mediated activity and slow disease progression in patients with PD or melanoma.
Assuntos
Lítio/farmacologia , Melanoma/prevenção & controle , Modelos Biológicos , Fármacos Neuroprotetores/farmacologia , Nicotiana/química , Doença de Parkinson/prevenção & controle , Fumantes , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/fisiologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/prevenção & controle , Autofagia/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta/fisiologia , Humanos , Incidência , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Lítio/análise , Lítio/uso terapêutico , Carbonato de Lítio/uso terapêutico , Melanoma/epidemiologia , Mutação , Fármacos Neuroprotetores/análise , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/biossíntese , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Doença de Parkinson/epidemiologia , Transtornos Parkinsonianos/tratamento farmacológico , Água/química , Via de Sinalização Wnt/fisiologia , alfa-Sinucleína/metabolismo , beta-Glucosidase/genéticaRESUMO
Over years, various biological constituents are isolated from Traditional Chinese Medicine and confirmed to show multifunctional activities. Magnolol, a hydroxylated biphenyl natural compound isolated from Magnolia officinalis, has been extensively documented and shows a range of biological activities. Many signaling pathways include, but are not limited to, NF-κB/MAPK, Nrf2/HO-1, and PI3K/Akt pathways, which are implicated in the biological functions mediated by magnolol. Thus, magnolol is considered as a promising therapeutic agent for clinic research. However, the low water solubility, the low bioavailability, and the rapid metabolism of magnolol dramatically limit its clinical application. In this review, we will comprehensively discuss the last five-year progress of the biological activities of magnolol, including anti-inflammatory, antimicroorganism, antioxidative, anticancer, neuroprotective, cardiovascular protection, metabolism regulation, and ion-mediating activity.
Assuntos
Compostos de Bifenilo/metabolismo , Compostos de Bifenilo/farmacologia , Lignanas/metabolismo , Lignanas/farmacologia , Medicina Tradicional Chinesa , Anti-Inflamatórios/análise , Antineoplásicos/análise , Antioxidantes/análise , Compostos de Bifenilo/química , Compostos de Bifenilo/uso terapêutico , Fármacos Cardiovasculares/análise , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Lignanas/química , Lignanas/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Magnolia/química , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Fármacos Neuroprotetores/análise , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Dietary phenolics are known for their potent antioxidant and anti-inflammatory activities, making them promising candidates for protection against neuroinflammation and neurodegeneration. Hydroalcohol extract of Egyptian species of Corchorus olitorius L. (Co) leaves was investigated for its neuroprotective effects in a lipopolysaccharide-induced neuroinflammatory mouse model. Twenty five metabolites were characterized from the bioactive extract using high-performance liquid chromatography HPLC/PDA/HRESI/MSn , revealing 1,5-dicaffeoylquinic acid (Co11) as one of the major constituents (5.7%), which was isolated and its identity was confirmed by spectral data as first report. Co significantly protected microglia against H2 O2 -induced cytotoxicity and immunohistochemistry showed reduced expression of the astrocytic marker, glial fibrillary acidic protein, and the inflammatory marker, cyclooxygenase-2. These findings correlated with significant improvement of cognitive functions and reduction of LPS-induced neurodegeneration in Co-treated mice as revealed by histopathology. The current study shows promising effects of Co in limiting neurodegeneration and cognitive impairment caused by neuroinflammation and glial cell activation. PRACTICAL APPLICATION: Information presented here shed light on the promising effects of Corchorus olitorius (Co) for the modulation of neuroinflammatory pathways improving the neuroinflammation-related neurodegeneration and cognitive decline. This makes Co a promising candidate as a nutraceutical supplement to be used against neuroinflammation-related disorders.
Assuntos
Disfunção Cognitiva/prevenção & controle , Corchorus/química , Dieta , Microglia/efeitos dos fármacos , Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Fenóis/uso terapêutico , Animais , Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/análise , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Cromatografia Líquida de Alta Pressão , Cinamatos/análise , Cinamatos/farmacologia , Cinamatos/uso terapêutico , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Egito , Proteína Glial Fibrilar Ácida/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos , Masculino , Camundongos , Microglia/metabolismo , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Fármacos Neuroprotetores/análise , Fármacos Neuroprotetores/farmacologia , Fenóis/análise , Fenóis/farmacologia , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta/químicaRESUMO
Camellia euphlebia is a new food source and traditional folk medicine in China. Previous studies have demonstrated the antidepressant activity of Camellia euphlebia extract by both in vivo and in vitro experiments. The effects of different pretreatments on phytochemical contents and neuroprotective activity of Camellia euphlebia extract were further investigated in order to develop an optimal processing method that makes the extraction more efficient. Six different powders of Camellia euphlebia leaves were prepared by different pretreatments. The particle size and morphology were examined by using a Malvern particle size analyzer and scanning electron microscopy, respectively. The results showed that the percentage of powder particle size within a range of 0.2â¼40 µm was up to 79.18% after press-shear assisted interaction technology pretreatment by 2% addition of shellfish shell powder, and the cells were broken completely. Additionally, the contents of flavonoids, polysaccharides, polyphenols, saponins, and catechin in the extract were 11.78 ± 0.62%, 34.60 ± 3.37%, 6.15 ± 0.29%, 9.43 ± 1.19%, and 1.99 ± 0.11%, respectively, which were higher than those of the other five extracts. Moreover, the extract had the strongest neuroprotective activity by comparing the neuroprotective effect of different extracts on corticosterone-induced neurotoxicity in differentiated PC12 cells. It is concluded that press-shear assisted interaction technology with 2% addition of shellfish shell powder pretreatment, to a great extent, improved the dissolution of bioactive ingredients in Camellia euphlebia.
Assuntos
Camellia/química , Fármacos Neuroprotetores/análise , Fármacos Neuroprotetores/química , Compostos Fitoquímicos/química , Extratos Vegetais/química , Folhas de Planta/química , Animais , Antidepressivos/química , Antidepressivos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Catequina/química , Catequina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Corticosterona/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Células PC12 , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Polifenóis/química , Polifenóis/farmacologia , Ratos , Saponinas/química , Saponinas/farmacologiaRESUMO
Tagetes erecta L. has long been consumed for culinary and medicinal purposes in different countries. The aim of this study was to explore the potential benefits from two cultivars of T. erecta related to its polyphenolic profile as well as antioxidant and anti-aging properties. The phenolic composition was analyzed by LC-DAD-ESI/MSn. Folin-Ciocalteu, DPPH·, and FRAP assays were performed in order to evaluate reducing antiradical properties. The neuroprotective potential was evaluated using the enzymes acetylcholinesterase and monoamine oxidase. Caenorhabditis elegans was used as an in vivo model to assess extract toxicity, antioxidant activity, delayed aging, and reduced ß-amyloid toxicity. Both extracts showed similar phenolic profiles and bioactivities. The main polyphenols found were laricitin and its glycosides. No acute toxicity was detected for extracts in the C. elegans model. T. erecta flower extracts showed promising antioxidant and neuroprotective properties in the different tested models. Hence, these results may add some information supporting the possibilities of using these plants as functional foods and/or as nutraceutical ingredients.
Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fenóis/farmacologia , Polifenóis/farmacologia , Tagetes/química , Acetilcolinesterase/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Antioxidantes/análise , Compostos de Bifenilo/metabolismo , Caenorhabditis elegans/metabolismo , Flores/química , Alimento Funcional , Glicosídeos/análise , Glicosídeos/farmacologia , Modelos Animais , Monoaminoxidase/metabolismo , Fármacos Neuroprotetores/análise , Fenóis/análise , Picratos/metabolismo , Extratos Vegetais/farmacologia , Plantas Comestíveis , Polifenóis/análise , Especificidade da Espécie , Tagetes/classificaçãoRESUMO
Bojungikgi-tang (BJIGT; Bu Zhong Yi Qi Tang in China, Hochuekkito in Japan) is a traditional Oriental herbal formula comprised of eight medicinal herbs that has long been used for the treatment of digestive disorders. A recent clinical study from South Korea reported that BJIGT-gamibang administration may be effective in treating dementia. We aimed to establish scientific evidence for the anti-dementia effects of BJIGT using in vitro and in vivo experimental models. We measured amyloid- ß (Aß) aggregation, ß-secretase (BACE), and antioxidant activity in a cell free system. Neuroprotective effects were assessed using CCK-8. Imprinting control region (ICR) mice were divided into the following six groups: Normal control, Aß-injected, Aß-injection + oral BJIGT gavage (200, 400, or 800 mg/kg/day), and Aß-injection + oral morin administration (10 mg/kg/day). Subsequently, behavioral evaluations were conducted and brain samples were collected from all the animals and assessed. BJIGT enhanced inhibition of Aß aggregation and BACE activity in vivo, as well as antioxidant activity in in vitro, cell-free systems. BJIGT also exerted neuroprotective effects in a hydroperoxide (H2O2)-induced damaged HT22 hippocampal cell line model. In addition, BJIGT administration significantly ameliorated cognitive impairments in Aß-injected mice, as assessed by the passive avoidance and Y-maze tests. Furthermore, BJIGT treatment suppressed Aß aggregation and expression, as well as expression of Aß, NeuN, and brain-derived neurotrophic factor (BDNF) in the hippocampi of Aß-injected mice. Overall, our results demonstrate that, with further testing in clinical populations, BJIGT may have great utility for the treatment of dementia and especially Alzheimer's disease.
Assuntos
Doença de Alzheimer/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Memória/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fármacos Neuroprotetores/análise , Fármacos Neuroprotetores/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Eerdun Wurile (EW) is one of the key Mongolian medicines for treatment of neurological and cardiological disorders. EW is ranked most regularly used Mongolian medicine in clinic. Components of EW which mainly originate from natural products are well defined and are unique to Mongolian medicine. AIM OF THE STUDY: Although the recipe of EW contains known neuroactive chemicals originated from plants, its mechanism of action has never been elucidated at molecular level. The objective of the present study is to explore the mechanism of neuroregenerative activity of EW by focusing on the regulation of gene expression in the brain of rat model of stroke. MATERIALS AND METHODS: Rat middle cerebral artery occlusion (MCAO) models were treated with EW for 15 days. Then, total RNAs from the cerebral cortex of rat MCAO models treated with either EW or control (saline) were extracted and analyzed by transcriptome sequencing. Differentially expressed genes were analyzed for their functions during the recovery of ischemic stroke. The expression level of significantly differentially expressed genes such as growth factors, microglia markers and secretive enzymes in the lesion was further validated by RT-qPCR and immunohistochemistry. RESULTS: Previously identified neuroactive compounds, such as geniposide (Yu et al., 2009), myristicin (Shin et al., 1988), costunolide (Okugawa et al., 1996), toosendanin (Shi and Chen, 1999) were detected in EW formulation. Bederson scale indicated that the treatment of rat MCAO models with EW showed significantly lowered neurological deficits (pâ¯<â¯0.01). The regional cerebral blood circulation was also remarkably higher in rat MCAO models treated with EW compared to the control group. A total of 186 genes were upregulated in the lesion of rat MCAO models treated with EW compared to control group. Among them, growth factors such as Igf1 (pâ¯<â¯0.05), Igf2 (pâ¯<â¯0.01), Grn (pâ¯<â¯0.01) were significantly upregulated in brain after treatment of rat MCAO models with EW. Meanwhile, greatly enhanced expression of microglia markers, as well as complementary components and secretive proteases were also detected. CONCLUSION: Our data collectively indicated that EW enhances expression of growth factors including Igf1 and Igf2 in neurons and microglia, and may stimulate microglia polarization in the brain. The consequences of such activity include stimulation of neuron growth, hydrolysis and clearance of cell debris at the lesion, as well as the angiogenesis.
Assuntos
Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Exsudatos de Plantas/uso terapêutico , Animais , Encéfalo/irrigação sanguínea , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Circulação Cerebrovascular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Infarto da Artéria Cerebral Média/fisiopatologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Fígado/anatomia & histologia , Fígado/efeitos dos fármacos , Masculino , Medicina Tradicional da Mongólia , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/análise , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/uso terapêutico , Exsudatos de Plantas/análise , Ratos WistarRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Akebia quinata Decaisne extract (AQE; Lardizabalaceae) is used in traditional herbal medicine for stress- and fatigue-related depression, improvement of fatigue, and mental relaxation. AIM OF THE STUDY: To clarify the effects of AQE on stress-induced fatigue, we investigated the neuroprotective pharmacological effects of A. quinata Decaisne in mice exposed to chronic restraint stress. MATERIALS AND METHODS: Seven-week old C57BL/6 mice chronically stressed by immobilization for 3â¯h daily for 15â¯d and non-stressed control mice underwent daily oral administration of AQE or distilled water. The open field, sucrose preference, and forced swimming behavioral tests were carried out once weekly, and immunohistochemical analyses of NeuN, brain-derived neurotrophic factor (BDNF), phosphorylated cAMP response element-binding (CREB) protein, and BDNF receptor tropomyosin receptor kinase B (TrkB) in striatum and hippocampus were performed at the end of the experimental period. Brain levels of serotonin, adrenaline, and noradrenaline as well as serum levels of corticosterone were measured. RESULTS: Behavioral tests showed that treatment with AQE improved all lethargic behaviors examined. AQE significantly attenuated the elevated levels of adrenaline, noradrenaline, and serotonin in the brain and corticosterone, alanine transaminase, and aspartate transaminase levels in the serum. Histopathological analysis showed that AQE reduced liver injury and lateral ventricle size in restraint-stress mice via inhibition of neuronal cell death. Immunohistochemical analysis showed increased phosphorylation of CREB and expression of BDNF and its receptor TrkB in striatum and hippocampus. Chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C were identified as the primary components of AQE. All three agents increased expression of BDNF in SH-SY5Y cells and PC12 cells with H2O2-induced neuronal cell damage. CONCLUSIONS: AQE may have a neuroprotective effect and ameliorate the effects of stress and fatigue-associated brain damage through mechanisms involving regulation of BDNF-TrkB signaling.
Assuntos
Fadiga/tratamento farmacológico , Magnoliopsida , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/uso terapêutico , Estresse Psicológico/tratamento farmacológico , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/análise , Ácido Clorogênico/uso terapêutico , Corticosterona/sangue , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas de Ligação a DNA , Fadiga/sangue , Humanos , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/metabolismo , Fármacos Neuroprotetores/análise , Proteínas Nucleares/metabolismo , Extratos Vegetais/análise , Proteínas Tirosina Quinases/metabolismo , Ratos , Restrição Física , Estresse Psicológico/sangueRESUMO
The link between obesity-induced systemic inflammation and decreased insulin signalling is well-known. It is also known that peripherally produced inflammatory cytokines can cross the blood-brain barrier, resulting in the release of neurotoxins that can ultimately lead to the demise of central nervous system integrity. A high-mesembrine Sceletium tortuosum extract was recently shown to possess cytoprotective and mild anti-inflammatory properties in monocytes and to target specific p450 enzymes to reduce adrenal glucocorticoid synthesis. This is significant since the aetiology of both obesity and diabetes is linked to inflammation and excess glucocorticoid production. Given the interlinked nature of glucocorticoid action and inflammation, central immunomodulatory effects of two Sceletium tortuosum extracts prepared by different extraction methods were investigated. Human astrocytes were pre-treated for 30 min, before exposure to Escherichia coli lipopolysaccharide for 23.5 h (in the presence of treatment). Cytotoxicity, mitotoxicity and cytokine responses (basally and in response to inflammatory stimulus) were assessed. In addition, total polyphenol content, antioxidant capacity and selected neural enzyme inhibition capacity were assessed for both extracts. The high-mesembrine Sceletium extract exerted cytoprotective and anti-inflammatory effects. In contrast, the high delta7-mesembrenone extract, rich in polyphenols, exhibited potent antioxidant effect, although with relatively higher risk of adverse effects with overdose. We conclude that both Sceletium tortuosum extracts may be employed as either a preventative supplement or complimentary treatment in the context of obesity and diabetes; however, current data also highlights the impact that extraction methods can have on plant product mechanism of action.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Astrócitos/efeitos dos fármacos , Alcaloides Indólicos/farmacologia , Mesembryanthemum/química , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Acetilcolinesterase/metabolismo , Anti-Inflamatórios não Esteroides/análise , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Antioxidantes/análise , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Astrócitos/imunologia , Astrócitos/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Inibidores da Colinesterase/análise , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Descoberta de Drogas , Inibidores Enzimáticos/análise , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Etnofarmacologia , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/metabolismo , Humanos , Alcaloides Indólicos/análise , Alcaloides Indólicos/química , Lipopolissacarídeos/toxicidade , Medicinas Tradicionais Africanas , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Proteínas do Tecido Nervoso/análise , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/isolamento & purificação , Proteínas do Tecido Nervoso/farmacologia , Fármacos Neuroprotetores/análise , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificaçãoRESUMO
Endoplasmic reticulum (ER) stress-related unfolded peptide accumulation is closely associated with the development of neurodegenerative diseases known as protein misfolding disorders. The antioxidative properties of kimchi, a traditional Korean fermented vegetable dish, have been well established. In this study, the neuroprotective effects of the kimchi methanol extract (KME) were examined in high-cholesterol diet (HCD)-fed mice. The animals were fed a HCD, with oral administration of either KME (KME group, 200 mg·kg bw-1·day-1, n = 10) or distilled water (Control group, n = 10) for 8 weeks. Compared with the levels in the control group, the reactive oxygen species, peroxynitrite, and lipid peroxidation levels in the brain were significantly decreased in the KME group (P < .05), whereas the glutathione level was increased (P < .05). In addition, the ER stress biomarkers, phospho-eukaryotic initiation factor 2 subunit α, glucose-regulated protein 78, X-box binding protein 1, inositol-requiring enzyme 1, and C/EBP homologous protein and the nuclear factor-kappaB-mediated inflammation were significantly reduced in the KME group (P < .05). In contrast, the expression levels of antioxidative enzymes regulated by nuclear factor erythroid 2-related factor-2 were elevated (P < .05). The amyloid-beta expression levels of the KME group were lower than that of the control group (P < .05). Moreover, the expression levels of Bcl-2-associated X, and caspases-3 and -9 were downregulated, with a concomitant upregulation of B cell lymphoma 2 (P < .05). Accordingly, KME provide neuronal cell protection via suppressing ER stress and caspase cascade signaling.
Assuntos
Caspases/metabolismo , Estresse do Retículo Endoplasmático , Alimentos Fermentados/análise , Fármacos Neuroprotetores/análise , Extratos Vegetais/farmacologia , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Biomarcadores/sangue , Encéfalo/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Colesterol/sangue , Colesterol na Dieta/administração & dosagem , Citoproteção , Dieta Hiperlipídica , Chaperona BiP do Retículo Endoplasmático , Regulação da Expressão Gênica , Glutationa/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Peroxidação de Lipídeos , Masculino , Metanol/química , Camundongos , Camundongos Knockout , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo , Ácido Peroxinitroso/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , República da Coreia , Triglicerídeos/sangue , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Oxidative stress, a predominant cause of apoptosis cascades triggered in neurodegenerative disorders, has been regarded as a critical inducement in the pathogenesis of Alzheimer's disease (AD). Gou Teng-San (GTS) is a traditional Chinese herbs preparation commonly utilized to alleviate cognitive dysfunction and psychological symptoms of patients with dementia. The present study aimed to investigate the protective effects of GTS40, an active fraction of GTS, on H2O2-induced oxidative damage and identify the potential active ingredients. Our results revealed that GTS40 exhibited radical scavenging activity, elevated cell viability, decreased the levels of intracellular reactive oxygen species (ROS), and stabilized mitochondrial transmembrane potential (MMP) in H2O2-treated PC12 cells. In addition, GTS40 blocked the apoptotic cascade by reversing the imbalance of Bcl-2/Bax and inhibiting the activity of caspase-3. Furthermore, an HPLC-QTOFMS method was developed to characterize major chemical constituents in GTS40. Our results revealed twenty-seven identified or tentatively characterized compounds through comparing their retention time (tR) and MS spectra with reference standards. These results suggested that GTS40 was a promising active fraction that may be beneficial in the prevention and treatment of oxidative stress-mediated neurodegenerative disorders.
Assuntos
Antioxidantes/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Peróxido de Hidrogênio/toxicidade , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Antioxidantes/análise , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Medicamentos de Ervas Chinesas/análise , Neurônios/citologia , Neurônios/metabolismo , Fármacos Neuroprotetores/análise , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
CONTEXT: The leaves of Pyrola decorate H. Andr (Pyrolaceae), known as Luxiancao, have long been used for treating kidney deficiency, gastric haemorrhage and rheumatic arthritic diseases in traditional Chinese medicine. OBJECTIVE: The phytochemicals and antioxidant capacities in vitro of P. decorate leaves were investigated. MATERIALS AND METHODS: Ethanol, petroleum ether, acetidin, n-butyl alcohol and aqueous extracts of Pyrola decorate leaves were prepared by solvent sequential process, and then isolated and purified to obtain phytochemicals. Cell viability was measured by MTT assay. PC12 cells were pretreated for 24 h with different extractions of P. decorate leaves at concentrations of 0.1, 0.5, 1, 5 and 10 mg/mL, then H2O2 of 0.4 mM was added in all samples for an additional 2 h. The antioxidant capacities of betulin, ursolic acid and monotropein were determined in PC12 cells against H2O2 induced cytotoxicity in vitro as well. RESULTS: Nine compounds (1-9) were isolated and structurally determined by spectroscopic methods, especially 2D NMR analyses. Ethanol extract treated groups showed inhibitory activity with IC50 value of 10.83 mg/mL. Betulin, ursolic acid and monotropein were isolated from P. decorate, and demonstrated with IC50 values of 6.88, 6.15 and 6.13 µg/mL, respectively. DISCUSSION AND CONCLUSIONS: In conclusion, Pyrola decorate is a potential antioxidative natural plant and worth testing for further pharmacological investigation in the treatment of oxidative stress related neurological disease.
Assuntos
Antioxidantes/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Pyrola/química , Animais , Antioxidantes/análise , Antioxidantes/química , Antioxidantes/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , China , Etanol/química , Etnofarmacologia , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/toxicidade , Iridoides/análise , Iridoides/química , Iridoides/isolamento & purificação , Iridoides/farmacologia , Estrutura Molecular , Neurônios/citologia , Fármacos Neuroprotetores/análise , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Oxidantes/antagonistas & inibidores , Oxidantes/toxicidade , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Ratos , Solventes/química , Triterpenos/análise , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Ácido UrsólicoRESUMO
Neuroprotective potential of V. teucrium and V. jacquinii methanol extracts was analyzed. Chemical analysis of investigated extracts showed the presence of phenolic acid derivatives, flavonoids and one secoiridoid. The detected flavonoids derived from flavones (luteolin and isoscutellarein in V. jacquinii; apigenin, isoscutellarein and luteolin in V. teucrium) and flavonol (quercetin in V. jacquinii). Acteoside was the dominant compound in V. jacquinii, while plantamajoside and isoscutellarein 7-O-(6â´-O-acetyl)-ß-allosyl (1â´â2â´)-ß-glucoside were the major phenolics in V. teucrium. Additionally, the antineurodegenerative activity was tested at concentrations of 25, 50, and 100 µg/ml using acetylcholinesterase (AChE) and tyrosinase (TYR) assays. The inhibition of both enzymes was achieved with the investigated extracts, ranging from 22.78 to 35.40% for AChE and from 9.57 to 16.38% for TYR. There was no statistical difference between the activities of the analyzed extracts. Our data indicate that V. teucrium and V. jacquinii may have beneficial effects against Alzheimer's and Parkinson's disease.