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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.
Expert Opin Ther Targets ; 25(6): 435-449, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34236922

RESUMO

Introduction: Despite the availability of new vaccines for SARS-CoV-2, there has been slow uptake and problems with supply in some parts of the world. Hence, there is still a necessity for drugs that can prevent hospitalization of patients and reduce the strain on health care systems. Drugs with sigma affinity potentially provide protection against the most severe symptoms of SARS-COV-2 and could prevent mortality via interactions with the sigma-1 receptor.Areas covered: This review examines the role of the sigma-1 receptor and autophagy in SARS-CoV-2 infections and how they may be linked. The authors reveal how sigma ligands may reduce the symptoms, complications, and deaths resulting from SARS-CoV-2 and offer insights on those patient cohorts that may benefit most from these drugs.Expert opinion: Drugs with sigma affinity potentially offer protection against the most severe symptoms of SARS-CoV-2 via interactions with the sigma-1 receptor. Agonists of the sigma-1 receptor may provide protection of the mitochondria, activate mitophagy to remove damaged and leaking mitochondria, prevent ER stress, manage calcium ion transport, and induce autophagy to prevent cell death in response to infection.


Assuntos
Antivirais/uso terapêutico , Autofagia , COVID-19/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Receptores sigma/fisiologia , COVID-19/mortalidade , COVID-19/virologia , Humanos , SARS-CoV-2/isolamento & purificação
5.
Expert Opin Ther Targets ; 25(5): 401-414, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34110944

RESUMO

INTRODUCTION: Autophagy is a cellular catabolic mechanism that helps clear damaged cellular components and is essential for normal cellular and tissue function. The sigma-1 receptor (σ-1R) is a chaperone protein involved in signal transduction, neurite outgrowth, and plasticity, improving memory, and neuroprotection. Recent evidence shows that σ-1R can promote autophagy. Autophagy activation by the σ-1Rs along with other neuroprotective effects makes it an interesting target for the treatment of Alzheimer's disease. AF710B, T-817 MA, and ANAVEX2-73 are some of the σ-1R agonists which have shown promising results and have entered clinical trials. These molecules have also been found to induce autophagy and show cytoprotective effects in cellular models. AREAS COVERED: This review provides insight into the current understanding of σ-1R functions related to autophagy and their role in alleviating AD. EXPERT OPINION: We propose a mechanism through which the activation of σ-1R and autophagy could alter amyloid precursor protein processing to inhibit amyloid-ß production by reconstituting cholesterol and gangliosides in the lipid raft to offer neuroprotection against AD. Future AD treatment could involve the combined targeting of the σ-1R and autophagy activation. We suggest that future studies investigate the link between autophagy the σ-1R and AD.

6.
Int J Mol Sci ; 22(6)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808935

RESUMO

Antioxidant agents are promising pharmaceuticals to prevent salivary gland (SG) epithelial injury from radiotherapy and their associated irreversible dry mouth symptoms. Epigallocatechin-3-gallate (EGCG) is a well-known antioxidant that can exert growth or inhibitory biological effects in normal or pathological tissues leading to disease prevention. The effects of EGCG in the various SG epithelial compartments are poorly understood during homeostasis and upon radiation (IR) injury. This study aims to: (1) determine whether EGCG can support epithelial proliferation during homeostasis; and (2) investigate what epithelial cells are protected by EGCG from IR injury. Ex vivo mouse SG were treated with EGCG from 7.5-30 µg/mL for up to 72 h. Next, SG epithelial branching morphogenesis was evaluated by bright-field microscopy, immunofluorescence, and gene expression arrays. To establish IR injury models, linear accelerator (LINAC) technologies were utilized, and radiation doses optimized. EGCG epithelial effects in these injury models were assessed using light, confocal and electron microscopy, the Griess assay, immunohistochemistry, and gene arrays. SG pretreated with EGCG 7.5 µg/mL promoted epithelial proliferation and the development of pro-acinar buds and ducts in regular homeostasis. Furthermore, EGCG increased the populations of epithelial progenitors in buds and ducts and pro-acinar cells, most probably due to its observed antioxidant activity after IR injury, which prevented epithelial apoptosis. Future studies will assess the potential for nanocarriers to increase the oral bioavailability of EGCG.


Assuntos
Células Acinares/efeitos dos fármacos , Células Acinares/efeitos da radiação , Catequina/análogos & derivados , Protetores contra Radiação/farmacologia , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/efeitos da radiação , Animais , Apoptose/efeitos dos fármacos , Catequina/farmacologia , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Humanos , Imuno-Histoquímica , Estresse Oxidativo , Lesões por Radiação/prevenção & controle
7.
Biology (Basel) ; 10(4)2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33810282

RESUMO

Kaempferia parviflora Wall. ex Baker (KP) or "Kra-chai-dam" has been shown to exhibit several pharmacological effects including anti-inflammation, antimicrobial, and sexual-enhancing activity. The objectives of this study included an investigation of the effect of KP rhizome extract against glutamate-induced toxicity in mouse hippocampal HT-22 neuronal cells, determination of the underlying mechanism of neuroprotection, and an evaluation of the effect of KP extract on the longevity of Caenorhabditis elegans. HT-22 cells were co-treated with glutamate (5 mM) and KP extract (25, 50, and 75 µg/mL) for 14 h. Cell viability, intracellular reactive oxygen species (ROS) assay, fluorescence-activated cell sorting (FACS) analysis, and Western blotting were performed. The longevity effect of KP extract on C. elegans was studied by lifespan measurement. In HT-22 cells, co-treatment of glutamate with KP extract significantly inhibited glutamate-mediated cytotoxicity and decreased intracellular ROS production. Additionally, the glutamate-induced apoptosis and apoptotic-inducing factor (AIF) translocation were blocked by KP extract co-treatment. Western blot analysis also demonstrated that KP extract significantly diminished extracellular signal-regulated kinase (ERK) phosphorylation induced by glutamate, and brain-derived neurotrophic factor (BDNF) was recovered to the control. Moreover, this KP extract treatment prolonged the lifespan of C. elegans. Altogether, this study suggested that KP extract possesses both neuroprotective and longevity-inducing properties, thus serving as a promising candidate for development of innovative health products.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33520685

RESUMO

Background and aim: Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now become the world pandemic. There is a race to develop suitable drugs and vaccines for the disease. The anti-HIV protease drugs are currently repurposed for the potential treatment of COVID-19. The drugs were primarily screened against the SARS-CoV-2 main protease. With an urgent need for safe and effective drugs to treat the virus, we have explored natural products isolated from edible and medicinal mushrooms that have been reported to possess anti-HIV protease. Experimental procedures: We have examined 36 compounds for their potential to be SARS-CoV-2 main protease inhibitors using molecular docking study. Moreover, drug-likeness properties including absorption, distribution, metabolism, excretion and toxicity were evaluated by in silico ADMET analysis. Results: Our AutoDock study showed that 25 of 36 candidate compounds have the potential to inhibit the main viral protease based on their binding affinity against the enzyme's active site when compared to the standard drugs. Interestingly, ADMET analysis and toxicity prediction revealed that 6 out of 25 compounds are the best drug-like property candidates, including colossolactone VIII, colossolactone E, colossolactone G, ergosterol, heliantriol F and velutin. Conclusion: Our study highlights the potential of existing mushroom-derived natural compounds for further investigation and possibly can be used to fight against SARS-CoV-2 infection. Taxonomy classification by evise: Disease, Infectious Disease, Respiratory System Disease, Covid-19, Traditional Medicine, Traditional Herbal Medicine, Phamaceutical Analysis.

9.
Sci Rep ; 11(1): 596, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436817

RESUMO

Bacopa monnieri (Linn.) Wettst. has been used in traditional medicine as a drug to enhance and improve memory. In this regard, this study aims to provide B. monnieri's efficacy as a neuroprotective drug and as a nootropic against various neurological diseases. Literatures were collected, following Prisma guidelines, from databases, including Scopus, PubMed, Google Scholar, and Science Direct and were scrutinized using a quality scoring system. Means, standard deviations and 'n' numbers were extracted from the metrics and analyzed. Jamovi computer software for Mac was used to carry out the meta-analysis. The selected studies suggested that the plant extracts were able to show some improvements in healthy subjects which were determined in Auditory Verbal Learning Task, digit span-reverse test, inspection time task and working memory, even though it was not significant, as no two studies found statistically significant changes in the same two tests. B. monnieri was able to express modest improvements in subjects with memory loss, wherein only a few of the neuropsychological tests showed statistical significance. B. monnieri in a cocktail with other plant extracts were able to significantly reduce the effects of Alzheimer's disease, and depression which cannot be solely credited as the effect of B. monnieri. Although in one study B. monnieri was able to potentiate the beneficial effects of citalopram; on the whole, currently, there are only limited studies to establish the memory-enhancing and neuroprotective effects of B. monnieri. More studies have to be done in the future by comparing the effect with standard drugs, in order to establish these effects clinically in the plant and corroborate the preclinical data.


Assuntos
Antidepressivos/farmacologia , Bacopa/química , Disfunção Cognitiva/prevenção & controle , Depressão/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Nootrópicos/farmacologia , Extratos Vegetais/farmacologia , Humanos , Metanálise como Assunto
10.
Sci Rep ; 11(1): 1241, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441873

RESUMO

Our recent study has shown that prenatal exposure to bisphenol A (BPA) altered the expression of genes associated with autism spectrum disorder (ASD). In this study, we further investigated the effects of prenatal BPA exposure on ASD-related genes known to regulate neuronal viability, neuritogenesis, and learning/memory, and assessed these functions in the offspring of exposed pregnant rats. We found that prenatal BPA exposure increased neurite length, the number of primary neurites, and the number of neurite branches, but reduced the size of the hippocampal cell body in both sexes of the offspring. However, in utero exposure to BPA decreased the neuronal viability and the neuronal density in the hippocampus and impaired learning/memory only in the male offspring while the females were not affected. Interestingly, the expression of several ASD-related genes (e.g. Mief2, Eif3h, Cux1, and Atp8a1) in the hippocampus were dysregulated and showed a sex-specific correlation with neuronal viability, neuritogenesis, and/or learning/memory. The findings from this study suggest that prenatal BPA exposure disrupts ASD-related genes involved in neuronal viability, neuritogenesis, and learning/memory in a sex-dependent manner, and these genes may play an important role in the risk and the higher prevalence of ASD in males subjected to prenatal BPA exposure.


Assuntos
Transtorno do Espectro Autista/metabolismo , Compostos Benzidrílicos/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/metabolismo , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Caracteres Sexuais , Animais , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/patologia , Feminino , Hipocampo/patologia , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/patologia , Ratos , Ratos Wistar
11.
Pharmaceuticals (Basel) ; 14(2)2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33513674

RESUMO

The tiger milk mushroom, Lignosus rhinocerus (LR), exhibits antioxidant properties, as shown in a few in vitro experiments. The aim of this research was to study whether three LR extracts exhibit antioxidant activities in Caenorhabditis elegans. In wild-type N2 nematodes, we determined the survival rate under oxidative stress caused by increased intracellular ROS concentrations. Transgenic strains, including TJ356, TJ375, CF1553, CL2166, and LD1, were used to detect the expression of DAF-16, HSP-16.2, SOD-3, GST-4, and SKN-1, respectively. Lifespan, lipofuscin, and pharyngeal pumping rates were assessed. Three LR extracts (ethanol, and cold and hot water) protected the worms from oxidative stress and decreased intracellular ROS. The extracts exhibited antioxidant properties through the DAF-16/FOXO pathway, leading to SOD-3 and HSP-16.2 modification. However, the expression of SKN-1 and GST-4 was not changed. All the extracts extended the lifespan. They also reduced lipofuscin (a marker for aging) and influenced the pharyngeal pumping rate (another marker for aging). The extracts did not cause dietary restriction. This novel study provides evidence of the functional antioxidant and anti-aging properties of LR. Further studies must confirm that they are suitable for use as antioxidant supplements.

12.
Nutrients ; 12(12)2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33317106

RESUMO

Rhinacanthus nasutus (L.) Kurz (Acanthaceae) (Rn) is an herbaceous shrub native to Thailand and much of South and Southeast Asia. It has several synonyms and local or common names. The root of Rn is used in Thai traditional medicine to treat snake bites, and the roots and/or leaves can be made into a balm and applied to the skin for the treatment of skin infections such as ringworm, or they may be brewed to form an infusion for the treatment of inflammatory disorders. Rn leaves are available to the public for purchase in the form of "tea bags" as a natural herbal remedy for a long list of disorders, including diabetes, skin diseases (antifungal, ringworm, eczema, scurf, herpes), gastritis, raised blood pressure, improved blood circulation, early-stage tuberculosis antitumor activity, and as an antipyretic. There have been many studies investigating the roles of Rn or compounds isolated from the herb regarding diseases such as Alzheimer's and other neurodegenerative diseases, cancer, diabetes and infection with bacteria, fungi or viruses. There have, however, been no clinical trials to confirm the efficacy of Rn in the treatment of any of these disorders, and the safety of these teas over long periods of consumption has never been tested. This review assesses the recent research into the role of Rn and its constituent compounds in a range of diseases.


Assuntos
Acanthaceae , Diabetes Mellitus/tratamento farmacológico , Infecções/tratamento farmacológico , Neoplasias/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Humanos , Folhas de Planta , Raízes de Plantas
13.
Pharmaceuticals (Basel) ; 13(10)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33007805

RESUMO

Citrus hystrix (CH) is a beneficial plant utilized in traditional folk medicine to relieve various health ailments. The antisenescent mechanisms of CH extracts were investigated using human neuroblastoma cells (SH-SY5Y). Phytochemical contents and antioxidant activities of CH extracts were analyzed using a gas chromatograph-mass spectrometer (GC-MS), 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) assay. Effects of CH extracts on high glucose-induced cytotoxicity, reactive oxygen species (ROS) generation, cell cycle arrest and cell cycle-associated proteins were assessed using a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay, non-fluorescent 2', 7'-dichloro-dihydrofluorescein diacetate (H2DCFDA) assay, flow cytometer and Western blot. The extracts protected neuronal senescence by inhibiting ROS generation. CH extracts induced cell cycle progression by releasing senescent cells from the G1 phase arrest. As the Western blot confirmed, the mechanism involved in cell cycle progression was associated with the downregulation of cyclin D1, phospho-cell division cycle 2 (pcdc2) and phospho-Retinoblastoma (pRb) proteins. Furthermore, the Western blot showed that extracts increased Surtuin 1 (SIRT1) expression by increasing the phosphorylation of Glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Collectively, CH extracts could protect high glucose-induced human neuronal senescence by inducing cell cycle progression and up-regulation of SIRT1, thus leading to the improvement of the neuronal cell functions.

14.
Cell Commun Signal ; 18(1): 161, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33036630

RESUMO

BACKGROUND: Toll-like receptor 3 (TLR3) ligand which activates TLR3 signaling induces both cancer cell death and activates anti-tumor immunity. However, TLR3 signaling can also harbor pro-tumorigenic consequences. Therefore, we examined the status of TLR3 in cholangiocarcinoma (CCA) cases to better understand TLR3 signaling and explore the potential therapeutic target in CCA. METHODS: The expression of TLR3 and receptor-interacting protein kinase 1 (RIPK1) in primary CCA tissues was assayed by Immunohistochemical staining and their associations with clinicopathological characteristics and survival data were evaluated. The effects of TLR3 ligand, Poly(I:C) and Smac mimetic, an IAP antagonist on CCA cell death and invasion were determined by cell death detection methods and Transwell invasion assay, respectively. Both genetic and pharmacological inhibition of RIPK1, RIPK3 and MLKL and inhibitors targeting NF-κB and MAPK signaling were used to investigate the underlying mechanisms. RESULTS: TLR3 was significantly higher expressed in tumor than adjacent normal tissues. We demonstrated in a panel of CCA cell lines that TLR3 was frequently expressed in CCA cell lines, but was not detected in a nontumor cholangiocyte. Subsequent in vitro study demonstrated that Poly(I:C) specifically induced CCA cell death, but only when cIAPs were removed by Smac mimetic. Cell death was also switched from apoptosis to necroptosis when caspases were inhibited in CCA cells-expressing RIPK3. In addition, RIPK1 was required for Poly(I:C) and Smac mimetic-induced apoptosis and necroptosis. Of particular interest, high TLR3 or low RIPK1 status in CCA patients was associated with more invasiveness. In vitro invasion demonstrated that Poly(I:C)-induced invasion through NF-κB and MAPK signaling. Furthermore, the loss of RIPK1 enhanced Poly(I:C)-induced invasion and ERK activation in vitro. Smac mimetic also reversed Poly(I:C)-induced invasion, partly mediated by RIPK1. Finally, a subgroup of patients with high TLR3 and high RIPK1 had a trend toward longer disease-free survival (p = 0.078, 28.0 months and 10.9 months). CONCLUSION: RIPK1 plays a pivotal role in TLR3 ligand, Poly(I:C)-induced cell death when cIAPs activity was inhibited and loss of RIPK1 enhanced Poly(I:C)-induced invasion which was partially reversed by Smac mimetic. Our results suggested that TLR3 ligand in combination with Smac mimetic could provide therapeutic benefits to the patients with CCA. Video abstract.

15.
Molecules ; 25(17)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32867388

RESUMO

Neurodegenerative disease is a collective term given for the clinical condition, which results in progressive degeneration of neurons and the loss of functions associated with the affected brain region. Apart from the increase in age, neurodegenerative diseases are also partly affected by diet and lifestyle practices. Parkinson's disease (PD) is a slow onset neurodegenerative disorder and the second most common neurodegenerative disease, which affects the motor system. Although there is no prescribed treatment method to prevent and cure PD, clinical procedures help manage the disease symptoms. Green tea polyphenols are known for several health benefits, including antioxidant, anti-inflammatory, and neuroprotective activity. The current manuscript summarizes the possible mechanisms of neuroprotective potential of green tea with a special focus on PD. Studies have suggested that the consumption of green tea protects against free-radicals, inflammation, and neuro-damages. Several in vivo studies aid in understanding the overall mechanism of green tea. However, the same dose may not be sufficient in humans to elicit similar effects due to complex physiological, social, and cultural development. Future research focused on more clinical trials could identify an optimum dose that could impart maximum health benefits to impart neuroprotection in PD.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/terapia , Polifenóis/farmacologia , Chá , Animais , Humanos , Camundongos , Neuroproteção
16.
Food Funct ; 11(9): 8179-8192, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32966472

RESUMO

Oolong tea, a traditional Chinese tea, is especially popular in south China and has a variety of health benefits. However, studies about its neuroprotective and neuroregenerative properties are still limited. This study explored the neuroprotective and neurite outgrowth-promoting properties of oolong tea in cultured neuronal cells (Neuro-2a and HT22) and Caenorhabditis elegans models. Ultra performance liquid chromatography was applied to identify the main natural bioactive compounds in oolong tea. Using Neuro-2a and HT22 cells, we found that oolong tea extracts had a protective effect against glutamate-induced cell death. The extracts reduced intracellular reactive oxygen species accumulation and induced gene expression of cellular antioxidant enzymes such as GPx, GSTs and SODs. These extracts also increased the average neurite length, and GAP-43 and Ten-4 mRNA expression in Neuro-2a cells. Moreover, they had protective effects against Aß-induced paralysis, chemotaxis deficiency and α-synuclein aggregation in C. elegans. This is the first study showing the neuroregenerative and neuroprotective potential of the oolong tea extracts against glutamate/Aß/α-synuclein-induced toxicity in vitro and in vivo. Our study may support oolong tea extracts as potential candidates for the prevention of neurodegenerative diseases.

17.
J Tradit Complement Med ; 10(5): 460-470, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32953562

RESUMO

Background: Neurodegenerative diseases, such as Alzheimer's disease, cause a great deal of suffering for both patients and carers. Bacopa monnieri (L.) wettst. Is known for its memory-enhancing properties, and is of great interest in treating neurodegenerative disease. Aims: This study aimed to evaluate B.monnieri against glutamate toxicity, and identify whether B.monnieri reduces mitochondrial and ER stress, as well as to measure B.monnieri's effect on the life span and aging of Caenorhabditis elegans. We hypothesized that B.monnieri would prevent cellular oxidative stress, prevent mitochondrial/ER stress, and increase the life span while reducing signs of aging in C.elegans. Experimental procedures: Glutamate toxicity was measured using viable cell staining assays and the MTT assay. ROS and mitochondrial stress were assessed by H2DCFDA and Rodamine123 staining, with fluorescence/confocal microscopy. C.elegans' median and maximum life span were measured, in response to B.monnieri treatment, along with lipofuscin imaging to measure the health of the C.elegans population. Results: B.monnieri hexane extract (but not ethanol extract) prevented the toxicity of 5 mM glutamate in HT-22 cells. We found that the mechanism involves the reduction of ROS production and the prevention of mitochondrial and ER stress. Furthermore, we showed that B.monnieri could increase the median and maximal lifespan of wild type C.elegans, maintain a younger appearing phenotype in the aged C.elegans. Conclusions: In conclusion, B.monnieri prevents mitochondrial, and oxidative stress in the cultured cells. Furthermore, it can prolong the healthy lifespan of C.elegans, indicating that B.monnieri the potential for therapeutic and preventative use in neurodegenerative disease.

18.
Expert Opin Ther Targets ; 24(10): 1009-1028, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32746649

RESUMO

INTRODUCTION: The sigma receptors are found abundantly in the central nervous system and are targets for the treatment of various diseases, including Alzheimer's (AD), Parkinson's (PD), Huntington's disease (HD), depression, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). However, for many of these diseases, other receptors and targets have been the focus of the most, such as acetylcholine esterase inhibitors in Alzheimer's and dopamine replacement in Parkinson's. The currently available drugs for these diseases have limited success resulting in the requirement of an alternative approach to their treatment. AREAS COVERED: In this review, we discuss the potential role of the sigma receptors and their ligands as part of a multi receptor approach in the treatment of the diseases mentioned above. The literature reviewed was obtained through searches in databases, including PubMed, Web of Science, Google Scholar, and Scopus. EXPERT OPINION: Given sigma receptor agonists provide neuroprotection along with other benefits such as potentiating the effects of other receptors, further development of multi-receptor targeting ligands, and or the development of multi-drug combinations to target multiple receptors may prove beneficial in the future treatment of degenerative diseases of the CNS, especially when coupled with better diagnostic techniques.


Assuntos
Encefalopatias/tratamento farmacológico , Terapia de Alvo Molecular , Receptores sigma/agonistas , Animais , Encefalopatias/fisiopatologia , Humanos , Ligantes , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Receptores sigma/metabolismo
19.
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.

20.
Sci Rep ; 10(1): 9251, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32514120

RESUMO

Sigma-1 and sigma-2 receptors are emerging therapeutic targets. We have identified that simple ammonium salts bind to these receptors and are effective in vivo. Radioligand binding assays were used to obtain structure-activity relationships of these salts. MTS assays were performed to determine their effect on growth in MCF7 and MDA-MB-486 cells. Anticancer properties were tested in NMRI mice transplanted with a fragment of mouse adenocarcinoma (MAC13). Antidepressant activity was tested using the forced-swim test and tail suspension tests. Dipentylammonium (Ki 43 nM), tripentylammonium (Ki 15 nM) and trihexylammonium (Ki 9 nM) showed high affinity for the sigma-1 receptor. Dioctanoylammonium had the highest affinity (K50 0.05 nM); this also showed the highest affinity for sigma-2 receptors (Ki 13 nM). Dipentylammonium was found to have antidepressant activity in vivo. Branched-chain ammonium salts showed lower affinity. Bis(2-ethylhexyl)ammonium (K50 29 µM), triisopentylammonium (K50 196 µM) and dioctanoylammonium showed a low Hill slope, and fitted a 2-site binding model for the sigma-1 receptor. We propose this two-site binding can be used to biochemically define a sigma-1 receptor antagonist. Bis(2-ethylhexyl)ammonium and triisopentylammonium were able to inhibit the growth of tumours in vivo. Cheap, simple ammonium salts act as sigma-1 receptor agonists and antagonists in vivo and require further investigation.


Assuntos
Compostos de Amônio/química , Compostos de Amônio/farmacologia , Depressão/tratamento farmacológico , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Receptores sigma/metabolismo , Sais/química , Compostos de Amônio/metabolismo , Compostos de Amônio/uso terapêutico , Antidepressivos/química , Antidepressivos/metabolismo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Cálcio/metabolismo , Proliferação de Células/efeitos dos fármacos , Depressão/metabolismo , Humanos , Células MCF-7 , Neoplasias/metabolismo
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