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1.
Nutrients ; 13(7)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34371875

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) have been recognized to cause neurobehavioral dysfunctions and disorder of cognition and behavioral patterns in childhood. Momordica charantia L. (MC) has been widely known for its nutraceutical and health-promoting properties. To date, the effect of MC for the prevention and handling of PAHs-induced neurotoxicity has not been reported. In the current study, the neuroprotective effects of MC and its underlying mechanisms were investigated in mouse hippocampal neuronal cell line (HT22); moreover, in silico analysis was performed with the phytochemicals MC to decipher their potential function as neuroprotectants. MC was demonstrated to possess neuroprotective effect by reducing reactive oxygen species' (ROS') production and down-regulating cyclin D1, p53, and p38 mitogen-activated protein kinase (MAPK) protein expressions, resulting in the inhibition of cell apoptosis and the normalization of cell cycle progression. Additionally, 28 phytochemicals of MC and their competence on inhibiting cytochrome P450 (CYP: CYP1A1, CYP1A2, and CYP1B1) functions were resolved. In silico analysis of vitamin E and stigmasterol revealed that their binding to either CYP1A1 or CYP1A2 was more efficient than the binding of each positive control (alizarin or purpurin). Together, MC is potentially an interesting neuroprotectant including vitamin E and stigmasterol as probable active components for the prevention for PAHs-induced neurotoxicity.


Assuntos
Hipocampo/efeitos dos fármacos , Momordica charantia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Estigmasterol/farmacologia , Vitamina E/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Camundongos , Momordica charantia/química , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Ligação Proteica , Espécies Reativas de Oxigênio/metabolismo , Estigmasterol/isolamento & purificação , Vitamina E/isolamento & purificação
2.
Nutrients ; 13(7)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201882

RESUMO

Tea is one of the most popular and widely consumed beverages worldwide, and possesses numerous potential health benefits. Herbal teas are well-known to contain an abundance of polyphenol antioxidants and other ingredients, thereby implicating protection and treatment against various ailments, and maintaining overall health in humans, although their mechanisms of action have not yet been fully identified. Autophagy is a conserved mechanism present in organisms that maintains basal cellular homeostasis and is essential in mediating the pathogenesis of several diseases, including cancer, type II diabetes, obesity, and Alzheimer's disease. The increasing prevalence of these diseases, which could be attributed to the imbalance in the level of autophagy, presents a considerable challenge in the healthcare industry. Natural medicine stands as an effective, safe, and economical alternative in balancing autophagy and maintaining homeostasis. Tea is a part of the diet for many people, and it could mediate autophagy as well. Here, we aim to provide an updated overview of popular herbal teas' health-promoting and disease healing properties and in-depth information on their relation to autophagy and its related signaling molecules. The present review sheds more light on the significance of herbal teas in regulating autophagy, thereby improving overall health.


Assuntos
Autofagia , Células/metabolismo , Saúde , Homeostase , Chás de Ervas , Animais , Humanos
3.
J Tradit Complement Med ; 10(3): 301-308, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32670825

RESUMO

Neurodegenerative diseases (NDD) are a range of debilitating conditions of the brain involving progressive loss of neurons, many of which are still currently incurable despite enormous efforts on drug discovery and development in the past decade. As NDD is closely linked to old age, the rapid worldwide growth in the aging population contributes to an increasing number of people with one of these incurable diseases and therefore it is considered a significant global health issue. There is an urgent need for novel effective treatments for NDD, and many new research strategies are centered on traditional medicine as an alternative or complementary solution. Several previous findings have suggested that glutamate toxicity drives neurodegeneration in many NDD, and the medicinal plants with anti-glutamate toxicity properties can be potentially used for their treatment. In order to obtain data relating to natural products against glutamate toxicity, six candidate plant species of Thailand were identified. Studies utilizing these herbs were searched for using the herb name (Latin and common names) along with the term "glutamate" in the following databases across all available years: PubMed, Scopus, and Google Scholar. This review emphasizes the importance of glutamate toxicity in NDD and summarizes individual plants and their active constituents with the mechanism of action against glutamate toxicity-mediated neuronal cell death that could be a promising resource for future NDD therapy. Taxonomy classification by evise: Alzheimer's disease, Neurodegenerative diseases, Cell culture, Molecular Biology, Traditional herbal medicine, Oxidative stress, Glutamate neurotransmitter.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33520683

RESUMO

Background and aim: The novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now become a worldwide pandemic bringing over 71 million confirmed cases, while the specific drugs and vaccines approved for this disease are still limited regarding their effectiveness and adverse events. Since virus incidences are still on rise, infectivity and mortality may also rise in the near future, natural products are highly considered to be valuable sources for the discovery of new antiviral drugs against SARS-CoV-2. This present review aims to comprehensively summarize the up-to-date scientific literatures on biological activities of plant- and mushroom-derived compounds relevant to mechanistic targets involved in SARS-CoV-2 infection and inflammatory-associated pathogenesis, including viral entry, replication and release, and the renin-angiotensin-aldosterone system (RAAS). Experimental procedure: Data were retrieved from a literature search available on PubMed, Scopus and Google Scholar databases and collected until the end of May 2020. The findings from in vitro cell and non-cell based studies were considered, while the results of in silico studies were excluded. Results and conclusion: Based on the previous findings in SARS-CoV studies, except in silico molecular docking analysis, herein, we provide a total of 150 natural compounds as potential candidates for development of new anti-COVID-19 drugs with higher efficacy and lower toxicity than the existing therapeutic agents. Several natural compounds have showed their promising actions on multiple therapeutic targets, which should be further explored. Among them, quercetin, one of the most abundant of plant flavonoids, is proposed as a lead candidate with its ability on the virus side to inhibit SARS-CoV spike protein-angiotensin-converting enzyme 2 (ACE2) interaction, viral protease and helicase activities, as well as on the host cell side to inhibit ACE activity and increase intracellular zinc level.

5.
BMC Complement Altern Med ; 19(1): 164, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286949

RESUMO

BACKGROUND: Caesalpinia mimosoides, a vegetable consumed in Thailand, has been reported to exhibit in vitro antioxidant properties. The in vivo antioxidant and anti-aging activities have not been investigated. The aim of this research was to study the antioxidant activity of C. mimosoides extracts in Caenorhabditis elegans, a widely used model organism in this context. METHODS: C. elegans were treated with C. mimosoides extracts in a various concentrations. To investigate the protective effects of the extract against oxidative stress, wild-type N2 were used to determine survival rate under oxidative stress and intracellular ROS. To study underlying mechanisms, the mutant strains with GFP reporter gene including TJ356, CF1553, EU1 and LD4 were used to study DAF-16, SOD-3, SKN-1 and GST-4 gene, respectively. Lifespan and aging pigment of the worms were also investigated. RESULTS: A leaf extract of C. mimosoides improved resistance to oxidative stress and reduced intracellular ROS accumulation in nematodes. The antioxidant effects were mediated through the DAF-16/FOXO pathway and SOD-3 expression, whereas the expression of SKN-1 and GST-4 were not altered. The extract also prolonged lifespan and decreased aging pigments, while the body length and brood size of the worms were not affected by the extract, indicating low toxicity and excluding dietary restriction. CONCLUSIONS: The results of this study establish the antioxidant activity of C. mimosoides extract in vivo and suggest its potential as a dietary supplement and alternative medicine to defend against oxidative stress and aging, which should be investigated in intervention studies.


Assuntos
Antioxidantes/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Caesalpinia/química , Longevidade/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Tamanho Corporal/efeitos dos fármacos , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/metabolismo , Flavonoides/análise , Sequestradores de Radicais Livres/farmacologia , Metanol , Naftoquinonas , Fenóis/análise , Folhas de Planta/química , Espécies Reativas de Oxigênio , Reprodução/efeitos dos fármacos
6.
BMC Complement Altern Med ; 18(1): 278, 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30326896

RESUMO

BACKGROUND: Acanthus ebracteatus (AE), an herb native to Asia, has been recognized in traditional folk medicine not only for its antioxidant properties and various pharmacological activities but also as an ingredient of longevity formulas. However, its anti-neurodegenerative potential is not yet clearly known. This work aimed to evaluate the protective effect of AE leaf extract against glutamate-induced oxidative damage in mouse hippocampal HT22 cells, a neurodegenerative model system due to a reduction in glutathione levels and an increase in reactive oxygen species (ROS). METHODS: Cell viability, apoptosis, and ROS assays were performed to assess the protective effect of AE leaf extract against glutamate-induced oxidative toxicity in HT22 cells. The antioxidant capacity of AE was evaluated using in vitro radical scavenging assays. The subcellular localization of apoptosis-inducing factor (AIF) and the mRNA and protein levels of genes associated with the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant system were determined to elucidate the mechanisms underlying the neuroprotective effect of AE leaf extract. RESULTS: We demonstrated that AE leaf extract is capable of attenuating the intracellular ROS generation and HT22 cell death induced by glutamate in a concentration-dependent manner. Co-treatment of glutamate with the extract significantly reduced apoptotic cell death via inhibition of AIF nuclear translocation. The increases in Nrf2 levels in the nucleus and gene expression levels of antioxidant-related downstream genes under Nrf2 control were found to be significant in cells treated with the extract. CONCLUSIONS: The results suggested that AE leaf extract possesses neuroprotective activity against glutamate-induced oxidative injury and may have therapeutic potential for the treatment of neurodegenerative diseases associated with oxidative stress.


Assuntos
Acanthaceae/química , Ácido Glutâmico/toxicidade , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Compostos de Bifenilo , Linhagem Celular , Camundongos , Picratos , Folhas de Planta/química
7.
BMC Complement Altern Med ; 18(1): 223, 2018 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-30041641

RESUMO

BACKGROUND: Streblus asper is a well-known plant native to Southeast Asia. Different parts of the plant have been traditionally used for various medicinal purposes. However, there is very little scientific evidence reporting its therapeutic benefits for potential treatment of Alzheimer's disease (AD). The study aimed to evaluate antibacterial, antioxidant, acetylcholinesterase (AChE) inhibition, and neuroprotective properties of S. asper leaf extracts with the primary objective of enhancing therapeutic applications and facilitating activity-guided isolation of the active chemical constituents. METHODS: The leaves of S. asper were extracted in ethanol and subsequently fractionated into neutral, acid and base fractions. The phytochemical constituents of each fraction were analyzed using GC-MS. The antibacterial activity was evaluated using a broth microdilution method. The antioxidant activity was determined using DPPH and ABTS radical scavenging assays. The neuroprotective activity against glutamate-induced toxicity was tested on hippocampal neuronal HT22 cell line by evaluating the cell viability using MTT assay. The AChE inhibitory activity was screened by thin-layer chromatography (TLC) bioautographic method. RESULTS: The partition of the S. asper ethanolic leaf extract yielded the highest mass of phytochemical constitutions in the neutral fraction and the lowest in the basic fraction. Amongst the three fractions, the acidic fraction showed the strongest antibacterial activity against gram-positive bacteria. The antioxidant activities of three fractions were found in the order of acidic > basic > neutral, whereas the decreasing order of neuroprotective activity was neutral > basic > acidic. TLC bioautography revealed one component in the neutral fraction exhibited anti-AChE activity. While in the acid fraction, two components showed inhibitory activity against AChE. GC-MS analysis of three fractions showed the presence of major phytochemical constituents including terpenoids, steroids, phenolics, fatty acids, and lipidic plant hormone. CONCLUSIONS: Our findings have demonstrated the therapeutic potential of three fractions extracted from S. asper leaves as a promising natural source for neuroprotective agents with additional actions of antibacterials and antioxidants, along with AChE inhibitors that will benefit in the development of new natural compounds in therapies against AD.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Inibidores da Colinesterase/farmacologia , Moraceae/química , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Animais , Antibacterianos/química , Antioxidantes/química , Bactérias/efeitos dos fármacos , Compostos de Bifenilo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Inibidores da Colinesterase/química , Cromatografia Gasosa-Espectrometria de Massas , Hipocampo/citologia , Camundongos , Fármacos Neuroprotetores/química , Picratos , Extratos Vegetais/análise , Extratos Vegetais/química , Folhas de Planta/química
8.
BMC Complement Altern Med ; 17(1): 551, 2017 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-29282044

RESUMO

BACKGROUND: Although such local herb as Streblus asper (family Moraceae) has long been recognized for traditional folk medicines and important ingredient of traditional longevity formula, its anti-neurodegeneration or anti-aging activity is little known. This study aimed to investigate the neuroprotective effect of S. asper leaf extracts (SA-EE) against toxicity of glutamate-mediated oxidative stress, a crucial factor contributing to the neuronal loss in age-associated neurodegenerative diseases and the underlying mechanism as well as to evaluate its longevity effect. METHODS: Using mouse hippocampal HT22 as a model for glutamate oxidative toxicity, we carried out MTT and LDH assays including Annexin V-FITC/propidium iodide staining to determine the SA-EE effect against glutamate-induced cell death. Antioxidant activities of SA-EE were evaluated using the radical scavenging and DCFH-DA assays. To elucidate the underlying mechanisms, SA-EE treated cells were analyzed for the expressions of mRNA and proteins interested by immunofluorescent staining, western blot analysis and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) techniques. The longevity effect of SA-EE was examined on C. elegans by lifespan assay. RESULTS: We demonstrate that a concentration-dependent reduction of glutamate-induced cytotoxicity was significant after SA-EE treatment as measured by MTT and LDH assays. Annexin V-FITC/propidium iodide and immunofluorescent staining showed that co-treatment of glutamate with SA-EE significantly reduced apoptotic-inducing factor (AIF)-dependent apoptotic cell death. DCFH-DA assay revealed that this extract was capable of dose dependently attenuating the ROS caused by glutamate. Western blot analysis and qRT-PCR showed that nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels in the nucleus, as well as mRNA levels of antioxidant-related genes under Nrf2 regulation were significantly increased by SA-EE. Furthermore, this extract was capable of extending the lifespan of C. elegans. CONCLUSIONS: SA-EE possesses both longevity effects and neuroprotective activity against glutamate-induced cell death, supporting its therapeutic potential for the treatment of age-associated neurodegenerative diseases.


Assuntos
Ácido Glutâmico/toxicidade , Moraceae , Neurônios/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caenorhabditis elegans , Linhagem Celular , Sobrevivência Celular , Etanol , Hipocampo/citologia , Longevidade/efeitos dos fármacos , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/citologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Folhas de Planta/química , Substâncias Protetoras/química , Transdução de Sinais/efeitos dos fármacos
9.
Artigo em Inglês | MEDLINE | ID: mdl-23762130

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to memory deficits and death. While the number of individuals with AD is rising each year due to the longer life expectancy worldwide, current therapy can only somewhat relieve the symptoms of AD. There is no proven medication to cure or prevent the disease, possibly due to a lack of knowledge regarding the molecular mechanisms underlying disease pathogenesis. Most previous studies have accepted the "amyloid hypothesis," in which the neuropathogenesis of AD is believed to be triggered by the accumulation of the toxic amyloid beta (A ß ) protein in the central nervous system (CNS). Lately, knowledge that may be critical to unraveling the hidden pathogenic pathway of AD has been revealed. This review concentrates on the toxicity of A ß and the mechanism of accumulation of this toxic protein in the brain of individuals with AD and also summarizes recent advances in the study of these accumulation mechanisms together with the role of herbal medicines that could facilitate the development of more effective therapeutic and preventive strategies.

10.
Int J Mol Sci ; 12(10): 6619-34, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22072907

RESUMO

Serotonin (5-HT) is a monoamine neurotransmitter and plays important roles in several of the human body's systems. Known as a primary target for psychoactive drug development, the 5-HT transporter (5-HTT, SERT) plays a critical role in the regulation of serotonergic function by reuptaking 5-HT. The allelic variation of 5-HTT expression is caused by functional gene promoter polymorphism with two principal variant alleles, 5-HTT gene-linked polymorphic region (5-HTTLPR). It has been demonstrated that 5-HTTLPR is associated with numerous neuropsychiatric disorders. The functional roles of 5-HTTLPR have been reported in human choriocarcinoma (JAR), lymphoblast and raphe cells. To date, the significance of 5-HTTLPR in gastrointestinal tract-derived cells has never been elucidated. Thus, the impact of 5-HTTLPR on 5-HTT transcription was studied in SW480 human colon carcinoma cells, which were shown to express 5-HTT. We found 42-bp fragment in long (L) allele as compared to short (S) allele, and this allelic difference resulted in 2-fold higher transcriptional efficiency of L allele (P < 0.05) as demonstrated using a functional reporter gene assay. Nevertheless, the transcriptional effect of estrogen and glucocorticoid on 5-HTT expression via 5-HTTLPR was not found in this cell line. Our study was the first to demonstrate the molecular role of this allelic variation in gastrointestinal tract cells.


Assuntos
Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Alelos , Sequência de Bases , Sítios de Ligação , Linhagem Celular Tumoral , Genes Reporter , Humanos , Regiões Promotoras Genéticas/efeitos dos fármacos , RNA Mensageiro/metabolismo , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/química , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Esteroides/farmacologia , Fatores de Transcrição/metabolismo , Transcrição Genética
11.
Mol Cell Neurosci ; 46(1): 200-12, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20851768

RESUMO

The neurobiological mechanisms of emotional modulation and the molecular pathophysiology of anxiety disorders are largely unknown. The fibroblast growth factor (FGF) family has been implicated in the regulation of many physiological and pathological processes, which include the control of emotional behaviors. The present study examined mice with a targeted deletion of the fgf-bp3 gene, which encodes a novel FGF-binding protein, in animal models relevant to anxiety. To define the behavioral consequences of FGF-BP3 deficiency, we evaluated fgf-bp3-deficient mice using anxiety-related behavioral paradigms that provide a conflict between the desire to explore an unknown area or objects and the aversion to a brightly lit open space. The fgf-bp3-deficient mice exhibited alterations in time spent in the central area of the open-field arena, were less active in the lit areas of a light/dark transition test, and had a prolonged latency to feed during a novelty-induced hypophagia test. These changes were associated with alterations in light-induced orbitofrontal cortex (OFC) activation in an extracellular signal-regulated kinase (ERK) pathway-dependent manner. These results demonstrate that FGF-BP3 is a potent mediator of anxiety-related behaviors in mice and suggest that distinct pathways regulate emotional behaviors. Therefore, FGF-BP3 plays a critical role in the regulation of emotional states and in the development of anxiety disorders and should be investigated as a therapeutic target for anxiety disease in humans.


Assuntos
Ansiedade/metabolismo , Comportamento Animal/fisiologia , Proteínas de Transporte/metabolismo , Animais , Ansiedade/genética , Proteínas de Transporte/genética , Linhagem Celular , Córtex Cerebral/citologia , Córtex Cerebral/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Peptídeos e Proteínas de Sinalização Intracelular , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Testes Neuropsicológicos
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