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1.
Food Chem ; 337: 127753, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32777566

RESUMO

The effects of treatment with melatonin on ripening of 'Fuji' apples during storage at 1 °C for 56 d were investigated. The apples were harvested at the commercial ripening stage and treated with 1 mmol L-1 melatonin. Compared with the control, melatonin treated apples had significant reduced ethylene production (28 d-56 d) and weight loss (14 d-56 d) during storage (p < 0.05). Also, the melatonin treatment maintained better apple skin structure throughout storage. The reduced ethylene production was regulated by the decreased expressions of MdACO1, MdACS1, MdAP2.4 and MdERF109, based on RNA-Seq analysis, which was validated using qRT-PCR analysis. Moreover, the activity of 3 enzymes, including peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT), were significantly increased in melatonin treated fruit (p < 0.05). Taken together, this study highlights the inhibitory effects of melatonin in ethylene biosynthesis and factors influencing postharvest quality in apple.


Assuntos
Etilenos/biossíntese , Qualidade dos Alimentos , Armazenamento de Alimentos/métodos , Frutas/efeitos dos fármacos , Malus/efeitos dos fármacos , Malus/metabolismo , Melatonina/farmacologia , Malus/enzimologia
2.
Anticancer Res ; 40(11): 6295-6303, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109567

RESUMO

BACKGROUND/AIM: The global prevalence of head and neck squamous cell carcinoma (HNSCC) remains high, and its prognosis poor. We investigated the anticancer effects of melatonin in human tongue squamous cell carcinoma cells (SCC-25) and its mechanisms of action. MATERIALS AND METHODS: MTT assay was used to determine cell viability. To assess the effects of melatonin on SCC-25 cell metastasis, we conducted cell formation, wound healing, transwell migration and invasion assay. Western blot analysis was performed to measure the levels of autophage marker proteins. RESULTS: We found that melatonin treatment significantly reduced the viability and colony formation ability of SCC-25 cells, impairing cell migration and invasion. Western blotting assay revealed that melatonin increased the levels of autophagy markers, such as LC-3B and Beclin-1. Consequently, melatonin induces autophage in SCC-25 cells. CONCLUSION: Melatonin may be a promising anticancer agent for the treatment of human tongue squamous cell carcinoma.


Assuntos
Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Carcinoma de Células Escamosas/patologia , Melatonina/farmacologia , Neoplasias da Língua/patologia , Apoptose/efeitos dos fármacos , Extratos Celulares , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Invasividade Neoplásica , Ensaio Tumoral de Célula-Tronco
3.
PLoS One ; 15(10): e0240149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33006999

RESUMO

From January 2020, COVID-19 is spreading around the world producing serious respiratory symptoms in infected patients that in some cases can be complicated by the severe acute respiratory syndrome, sepsis and septic shock, multiorgan failure, including acute kidney injury and cardiac injury. Cost and time efficient approaches to reduce the burthen of the disease are needed. To find potential COVID-19 treatments among the whole arsenal of existing drugs, we combined system biology and artificial intelligence-based approaches. The drug combination of pirfenidone and melatonin has been identified as a candidate treatment that may contribute to reduce the virus infection. Starting from different drug targets the effect of the drugs converges on human proteins with a known role in SARS-CoV-2 infection cycle. Simultaneously, GUILDify v2.0 web server has been used as an alternative method to corroborate the effect of pirfenidone and melatonin against the infection of SARS-CoV-2. We have also predicted a potential therapeutic effect of the drug combination over the respiratory associated pathology, thus tackling at the same time two important issues in COVID-19. These evidences, together with the fact that from a medical point of view both drugs are considered safe and can be combined with the current standard of care treatments for COVID-19 makes this combination very attractive for treating patients at stage II, non-severe symptomatic patients with the presence of virus and those patients who are at risk of developing severe pulmonary complications.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos , Melatonina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Piridonas/uso terapêutico , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Bases de Dados de Produtos Farmacêuticos , Furina/metabolismo , Humanos , Melatonina/farmacologia , Pandemias , Piridonas/farmacologia
4.
Mol Biol Rep ; 47(10): 8229-8233, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32920757

RESUMO

COVID-19 caused by the SARS-CoV-2 outbreak quickly has turned into a pandemic. However, no specific antiviral agent is yet available. In this communication, we aimed to evaluate the significance of CD147 protein and the potential protective effect of melatonin that is mediated by this protein in COVID-19. CD147 is a glycoprotein that is responsible for the cytokine storm in the lungs through the mediation of viral invasion. Melatonin use previously was shown to reduce cardiac damage by blocking the CD147 activity. Hence, melatonin, a safe drug, may prevent severe symptoms, reduce symptom severity and the adverse effects of the other antiviral drugs in COVID-19 patients. In conclusion, the use of melatonin, which is reduced in the elderly and immune-compromised patients, should be considered as an adjuvant through its CD147 suppressor and immunomodulatory effect.


Assuntos
Adjuvantes Farmacêuticos/uso terapêutico , Antivirais/uso terapêutico , Basigina/metabolismo , Infecções por Coronavirus/tratamento farmacológico , Melatonina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Antivirais/farmacologia , Basigina/antagonistas & inibidores , Infecções por Coronavirus/metabolismo , Humanos , Sistema Imunitário/efeitos dos fármacos , Melatonina/farmacologia , Pandemias , Pneumonia Viral/metabolismo , Transdução de Sinais/efeitos dos fármacos
5.
Acta Odontol Latinoam ; 33(2): 125, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32920615

RESUMO

Melatonin (MLT) is a potential signaling molecule in the homeostasis of bone metabolism and may be an important mediator of bone formation and stimulation. The aim of this in vitro study was to evaluate the effect of MLT on the viability, mRNA/protein expression and mineralization of pre-osteoblastic cells. The concentrations 5, 2.5, 1, 0.1 and 0.01 mM MLT were tested on pre-osteoblastic cells (MC3T3) compared to control (no MLT), evaluating proliferation and cell viability (C50), gene expression (RT-PCR) and secretion (ELISA) of COL-I and OPN at 24h, 48h and 72h, and the formation of mineral nodules (alizarin red and fast red) after 10 days of treatment. MLT at 5 and 2.5 mM proved to be cytotoxic (C50), so only 0.01, 0.1 and 1 mM were used for the subsequent analyses. OPN mRNA expression increased with MLT at 0.1 mM - 1 mM, which was followed by increased secretion of OPN both at 24h and 72h compared to the remaining groups (p <0.05). COL-I mRNA and COL-1 secretion followed the same pattern as OPN at 0.1 mM MLT at 72h of treatment (p <0.05). Regarding mineralization, all MLT doses (except 1mM) caused an increase (p <0.05) in the formation of mineral nodules compared to the control. Melatonin at 0.01mM - 1mM had a stimulatory effect on osteoblasts by upregulating COL-I and OPN expression/ secretion and mineralization, thereby fostering osteogenesis.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Metaloproteinase 2 da Matriz/metabolismo , Melatonina/farmacologia , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Osteopontina/metabolismo , Fragmentos de Peptídeos/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Ensaio de Imunoadsorção Enzimática , Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Metaloproteinase 2 da Matriz/genética , Osteoblastos/metabolismo , Osteopontina/genética , Fragmentos de Peptídeos/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real
6.
Int J Med Sci ; 17(14): 2133-2146, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922174

RESUMO

The SARS-CoV-2 spread quickly across the globe. The World Health Organization (WHO) on March 11 declared COVID-19 a pandemic. The mortality rate, hospital disorders and incalculable economic and social damages, besides the unproven efficacy of the treatments evaluated against COVID-19, raised the need for immediate control of this disease. Therefore, the current study employed in silico tools to rationally identify new possible SARS-CoV-2 main protease (Mpro) inhibitors. That is an enzyme conserved among the coronavirus species; hence, the identification of an Mpro inhibitor is to make it a broad-spectrum drug. Molecular docking studies described the binding sites and the interaction energies of 74 Mpro-ligand complexes deposited in the Protein Data Bank (PDB). A structural similarity screening was carried out in order to identify possible Mpro ligands that show additional pharmacological properties against COVID-19. We identified 59 hit compounds and among them, melatonin stood out due to its prominent immunomodulatory and anti-inflammatory activities; it can reduce oxidative stress, defence cell mobility and efficiently combat the cytokine storm and sepsis. In addition, melatonin is an inhibitor of calmodulin, an essential intracellular component to maintain angiotensin-converting enzyme 2 (ACE-2) on the cell surface. Interestingly, one of the most promising hits in our docking study was melatonin. It revealed better interaction energy with Mpro compared to ligands in complexes from PDB. Consequently, melatonin can have response potential in early stages for its possible effects on ACE-2 and Mpro, although it is also promising in more severe stages of the disease for its action against hyper-inflammation. These results definitely do not confirm antiviral activity, but can rather be used as a basis for further preclinical and clinical trials.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Descoberta de Drogas , Melatonina/farmacologia , Pneumonia Viral/tratamento farmacológico , Proteínas não Estruturais Virais/antagonistas & inibidores , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Cisteína Endopeptidases , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Melatonina/uso terapêutico , Simulação de Acoplamento Molecular , Pandemias , Pneumonia Viral/virologia , Inibidores de Proteases/farmacologia , Inibidores de Proteases/uso terapêutico
7.
Turk J Med Sci ; 50(6): 1504-1512, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-32777902

RESUMO

The aim of this review is to summarize current studies on the relationship between melatonin and aging. Nowadays, age-related diseases come into prominence, and identifying age-related changes and developing proper therapeutic approaches are counted as some of the major issues regarding community health. Melatonin is the main hormone of the pineal gland. Melatonin is known to influence many biological processes in the body, including circadian rhythms, the immune system, and neuroendocrine and cardiovascular functions.Melatoninrhythms also reflect the biological process of aging. Aging is an extremely complex and multifactorial process. Melatonin levels decline considerably with aging and its decline is associated with several age-related diseases. Aging is closely associated with oxidative damage and mitochondrial dysfunction. Free radical reactions initiated by the mitochondria constitute the inherent aging process. Melatonin plays a pivotal role in preventing age-related oxidative stress. Coronavirus disease 2019 (COVID-19) fatality rates increase with chronic diseases and age, where melatonin levels decrease. For this reason, melatonin supplementation in elderly could be beneficial in COVID-19 treatment. Therefore, studies on the usage of melatonin in COVID-19 treatment are needed.


Assuntos
Envelhecimento , Antioxidantes/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Melatonina/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Idoso , Envelhecimento/metabolismo , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Betacoronavirus , Infecções por Coronavirus/virologia , Suplementos Nutricionais , Humanos , Melatonina/metabolismo , Melatonina/farmacologia , Pandemias , Pneumonia Viral/virologia
8.
Virus Res ; 287: 198108, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-32768490

RESUMO

Viral infections are dangerous diseases for human health worldwide, which lead to significant morbidity and mortality each year. Because of their importance and the lack of effective therapeutic approaches, further attempts should be made to discover appropriate alternative or complementary treatments. Melatonin, a multifunctional neurohormone mainly synthesized and secreted by the pineal gland, plays some roles in the treatment of viral infections. Regarding a deadly outbreak of COVID-19 across the world, we decided to discuss melatonin functions against various viral infections including COVID-19. Therefore, in this review, we summarize current evidence on melatonin therapy for viral infections with focus on possible underlying mechanisms of melatonin actions.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/virologia , Melatonina/farmacologia , Pneumonia Viral/virologia , Antioxidantes , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Melatonina/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Pneumonia Viral/metabolismo , Transdução de Sinais/efeitos dos fármacos , Vacinação , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Viroses/tratamento farmacológico , Viroses/metabolismo , Viroses/virologia
9.
Biomolecules ; 10(9)2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32825327

RESUMO

There is a growing consensus that the antioxidant and anti-inflammatory properties of melatonin are of great importance in preserving the body functions and homeostasis, with great impact in the peripartum period and adult life. Melatonin promotes adaptation through allostasis and stands out as an endogenous, dietary, and therapeutic molecule with important health benefits. The anti-inflammatory and antioxidant effects of melatonin are intertwined and are exerted throughout pregnancy and later during development and aging. Melatonin supplementation during pregnancy can reduce ischemia-induced oxidative damage in the fetal brain, increase offspring survival in inflammatory states, and reduce blood pressure in the adult offspring. In adulthood, disturbances in melatonin production negatively impact the progression of cardiovascular risk factors and promote cardiovascular and neurodegenerative diseases. The most studied cardiovascular effects of melatonin are linked to hypertension and myocardial ischemia/reperfusion injury, while the most promising ones are linked to regaining control of metabolic syndrome components. In addition, there might be an emerging role for melatonin as an adjuvant in treating coronavirus disease 2019 (COVID 19). The present review summarizes and comments on important data regarding the roles exerted by melatonin in homeostasis and oxidative stress and inflammation related pathologies.


Assuntos
Adjuvantes Farmacêuticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Melatonina/administração & dosagem , Melatonina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adjuvantes Farmacêuticos/administração & dosagem , Adjuvantes Farmacêuticos/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Homeostase/efeitos dos fármacos , Humanos , Melatonina/farmacologia , Pandemias
10.
An Acad Bras Cienc ; 92(4): e20190981, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32844989

RESUMO

An emerging area in schizophrenia research focuses on the impact of immunomodulatory drugs such as melatonin, which have played important roles in many biological systems and functions, and appears to be promising. The objective was to evaluate the effect of melatonin on behavioral parameters in an animal model of schizophrenia. For this, Wistar rats were divided and used in two different protocols. In the prevention protocol, the animals received 1 or 10mg/kg of melatonin or water for 14 days, and between the 8th and 14th day they received ketamine or saline. In the reversal protocol, the opposite occurred. On the 14th day, the animals underwent behavioral tests: locomotor activity and prepulse inhibition task. In both protocols, the results revealed that ketamine had effects on locomotor activity and prepulse inhibition, confirming the validity of ketamine construction as a good animal model of schizophrenia. However, at least at the doses used, melatonin was not able to reverse/prevent ketamine damage. More studies are necessary to evaluate the role of melatonin as an adjuvant treatment in psychiatric disorders.


Assuntos
Suplementos Nutricionais , Melatonina , Esquizofrenia , Animais , Comportamento Animal , Modelos Animais de Doenças , Melatonina/farmacologia , Ratos , Ratos Wistar , Roedores , Esquizofrenia/tratamento farmacológico
11.
PLoS One ; 15(8): e0237536, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790719

RESUMO

Melatonin is effective in enhancing various abiotic stress resistances of plants. However, its underlying mechanisms in drought-resistance in winter wheat (Triticum aestivum L.) is not clear. The goal of this work was to investigate the effect of melatonin on seed germination and to evaluate leaf antioxidant physiology for two wheat varieties. Experiments included 20% PEG, melatonin plus 20% PEG and a control using two contrasting wheat varieties (JM22- drought sensitive and HG35- drought resistant). Melatonin levels were 0, 1, 10, 100 and 300 µmol L-1. Results revealed that 300 µmol L-1 of melatonin alleviated the negative effect of water stress on germination and increased radicle length, radicle number, and plumule length of the germinated seeds. Principal component analysis showed a significant change in amino acid content during germination and this change was dependent on melatonin concentration and the variety. Lysine (Lys) content in wheat seeds under the PEG plus 300 µmol L-1 melatonin treatment increased compared with that of the seeds under PEG alone. There was a significant and positive correlation between Lys content and morphological index of germination. During seedling growth, soluble protein was involved in osmotic adjustment and superoxide dismutase (SOD) activity was increased to mitigate the damage in the cytomembrane of JM 22 leaf under 300 µmol L-1 melatonin plus PEG treatment. The effect of melatonin was dependent on SOD activity increasing significantly for HG35-a drought resistant variety. The results of this work lays a foundation for further studies to determine if melatonin can be economically used to mitigate the impact of dry planting conditions on wheat productivity in North China Plain.


Assuntos
Antioxidantes/farmacologia , Germinação/efeitos dos fármacos , Melatonina/farmacologia , Polietilenoglicóis/toxicidade , Sementes/efeitos dos fármacos , Estresse Fisiológico , Triticum/efeitos dos fármacos , Secas , Osmose , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Triticum/crescimento & desenvolvimento , Triticum/metabolismo
12.
Eur J Pharmacol ; 882: 173329, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32615182

RESUMO

Coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a newly discovered highly pathogenic virus that was declared pandemic in March 2020 by the World Health Organization. The virus affects the respiratory system, produces an inflammatory storm that causes lung damage and respiratory dysfunction. It infects humans of all ages. The Covid-19 takes a more severe course in individuals with chronic metabolic diseases such as obesity, diabetes mellitus, and hypertension. This category of persons exhibits weak immune activity and decreased levels of endogenous antioxidants. Melatonin is a multifunctional signaling hormone synthesized and secreted primarily by the pineal gland. It is a potent antioxidant with immunomodulatory action and has remarkable anti-inflammatory effects under a variety of circumstances. Regarding Covid-19 and metabolic syndrome, adequate information about the relationship between these two comorbidities is required for better management of these patients. Since Covid-19 infection and complications involve severe inflammation and oxidative stress in people with obesity and diabetes, we anticipated the inclusion of melatonin, as powerful antioxidant, within proposed treatment protocols. In this context, melatonin is a potential and promising agent to help overcome Covid-19 infection and boost the immune system in healthy persons and obese and diabetic patients. This review summarizes some evidence from recently published reports on the utility of melatonin as a potential adjuvant in Covid-19-infected individuals with diabetes and obesity.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Diabetes Mellitus/imunologia , Melatonina/farmacologia , Obesidade/imunologia , Pneumonia Viral/tratamento farmacológico , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Diabetes Mellitus/epidemiologia , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Pulmão , Melatonina/uso terapêutico , Obesidade/epidemiologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Fatores de Risco , Resultado do Tratamento
13.
Life Sci ; 257: 118044, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32622944

RESUMO

AIMS: High-dose glucocorticoid (GC) administration causes osteoporosis. Many previous studies from our group and other groups have shown that melatonin participates in the regulation of osteoblast proliferation and differentiation, especially low concentrations of melatonin, which enhance osteoblast osteogenesis. However, the role of melatonin in glucocorticoid-induced osteoblast differentiation remains unknown. MATERIALS AND METHODS: An examination of the expression of osteoblast differentiation markers (ALP, OCN, COLL-1), as well as alkaline phosphatase staining and alkaline phosphatase enzymatic activity assay to measure osteoblast differentiation and quantifying Alizarin red S staining to measure mineralization, were performed to determine the effects of dexamethasone (Dex) and melatonin on the differentiation of MC3T3-E1 cells. We used immunofluorescence staining to detect the expression of Runx2 in melatonin-treated MC3T3-E1 cells. The expression of mRNA was determined by qRT-PCR, and protein levels were measured by western blotting. KEY FINDINGS: In the present study, we found that 100 µM Dex significantly reduced osteoblast differentiation and mineralization in MC3T3-E1 cells and that 1 µM melatonin attenuated these inhibitory effects. We found that only inhibition of PI3K/AKT (MK2206) and BMP/Smad (LDN193189) signalling abolished melatonin-induced differentiation and mineralization. Meanwhile, MK2206 decreased the expression of P-AKT and P-Smad1/5/9 and LDN193189 decreased the expression of P-Smad1/5/9 but had no obvious effect on P-AKT expression in melatonin-treated and Dex-induced MC3T3-E1 cells. SIGNIFICANCE: These findings suggest that melatonin rescues Dex-induced inhibition of osteoblast differentiation in MC3T3-E1 cells via the PI3K/AKT and BMP/Smad signalling pathways and that PI3K/AKT signalling may be the upstream signal of BMP/Smad signalling.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Melatonina/metabolismo , Osteoblastos/metabolismo , Animais , Biomineralização/efeitos dos fármacos , Proteína Morfogenética Óssea 2/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Linhagem Celular , Dexametasona/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/efeitos adversos , Glucocorticoides/farmacologia , Melatonina/farmacologia , Camundongos , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo
14.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 40(7): 958-964, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32701234

RESUMO

OBJECTIVE: To investigate the protective effect of melatonin against myocardial ischemia reperfusion (IR) injury in isolated rat hearts and explore the underlying mechanisms. METHODS: The isolated hearts from 40 male SD rats were randomly divided into 4 groups (n=10): the control group, where the hearts were perfused with KH solution for 175 min; IR group, where the hearts were subjected to global ischemia for 45 min followed by reperfusion for 120 min; IR+melatonin (Mel+IR) group, where melatonin (5 µmol/L) was administered to the hearts 1 min before ischemia and during the first 5 min of reperfusion, followed by 115 min of reperfusion; and IR+2, 3-butanedione monoxime (IR+BDM) group, where the hearts were treated with BDM (20 mmol/L) in the same manner as melatonin treatment. Myocardial injury in the isolated hearts was assessed based on myocardial injury area, caspase-3 activity, and expressions of cytochrome C and cleaved caspase-3 proteins. Cardiac contracture was assessed using HE staining and by detecting lactate dehydrogenase (LDH) activity and the content of cardiac troponin I (cTnI) in the coronary outflow, measurement of left ventricular end-diastolic pressure (LVEDP) and electron microscopy. The content of ATP in the cardiac tissue was also determined. RESULTS: Compared with those in the control group, the isolated hearts in IR group showed significantly larger myocardial injury area and higher caspase-3 activity and the protein expressions of cytochrome C and cleaved caspase-3 with significantly increased LDH activity and cTnI content in the coronary outflow and elevated LVEDP at the end of reperfusion; HE staining showed obvious fractures of the myocardial fibers and the content of ATP was significantly decreased in the cardiac tissue; electron microscopy revealed the development of contraction bands. In the isolated hearts with IR, treatment with Mel or BDM significantly reduced the myocardial injury area, caspase-3 activity, and protein expressions of cytochrome C and cleaved caspase-3, obviously inhibited LDH activity, lowered the content of cTnI and LVEDP, reduced myocardial fiber fracture, and increased ATP content in the cardiac tissue. Both Mel and BDM inhibited the formation of contraction bands in the isolated hearts with IR injury. CONCLUSIONS: Mel can alleviate myocardial IR injury in isolated rat hearts by inhibiting cardiac contracture, the mechanism of which may involve the upregulation of ATP in the cardiac myocytes to lessen the tear of membrane and reduce cell content leakage.


Assuntos
Coração , Melatonina , Contração Muscular , Traumatismo por Reperfusão Miocárdica , Animais , Coração/efeitos dos fármacos , Masculino , Melatonina/farmacologia , Melatonina/uso terapêutico , Contração Muscular/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
15.
PLoS One ; 15(7): e0236318, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726319

RESUMO

Lately, Drosophila has been favored as a model in sleep and circadian rhythm research due to its conserved mechanism and easily manageable operation. These studies have revealed the sophisticated parameters in whole-day sleep profiles of Drosophila, drawing connections between Drosophila sleep and human sleep. In this study, we tested several sleep deprivation protocols (mechanical shakes and light interruptions) on Drosophila and delineated their influences on Drosophila sleep. We applied a daytime light-deprivation protocol (DD) mimicking jet-lag to screen drugs that alleviate sleep deprivation. Characteristically, classical sleep-aid compounds exhibited different forms of influence: phenobarbital and pentobarbital modified total sleep time, while melatonin only shortened the latency to sleep. Such results construct the basis for further research on sleep benefits in other treatments in Drosophila. We screened seven herb extracts, and found very diverse results regarding their effect on sleep regulation. For instance, Panax notoginseng and Withania somnifera extracts displayed potent influence on total sleep time, while Melissa officinalis increased the number of sleep episodes. By comparing these treatments, we were able to rank drug potency in different aspects of sleep regulation. Notably, we also confirmed the presence of sleep difficulties in a Drosophila Alzheimer's disease (AD) model with an overexpression of human Abeta, and recognized clear differences between the portfolios of drug screening effects in AD flies and in the control group. Overall, potential drug candidates and receipts for sleep problems can be identified separately for normal and AD Drosophila populations, outlining Drosophila's potential in drug screening tests in other populations if combined with the use of other genetic disease tools.


Assuntos
Extratos Vegetais/farmacologia , Privação do Sono/tratamento farmacológico , Transtornos do Sono-Vigília/tratamento farmacológico , Sono/fisiologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/genética , Animais , Ritmo Circadiano/efeitos dos fármacos , Modelos Animais de Doenças , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , Drosophila melanogaster/fisiologia , Regulação da Expressão Gênica/genética , Humanos , Melatonina/farmacologia , Mutação , Panax notoginseng/química , Fenobarbital/farmacologia , Extratos Vegetais/química , Sono/efeitos dos fármacos , Sono/genética , Privação do Sono/genética , Privação do Sono/fisiopatologia , Transtornos do Sono-Vigília/genética , Transtornos do Sono-Vigília/fisiopatologia , Withania/química
17.
Toxicol Lett ; 332: 118-129, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32659471

RESUMO

Silver-based antimicrobials are widely used topically to treat infections associated with multi-drug resistant (MDR) pathogens. Expanding this topical use to aerosols to treat lung infections requires understanding and preventing silver toxicity in the respiratory tract. A key mechanism resulting in silver-induced toxicity is the production of reactive oxygen species (ROS). In this study, we have verified ROS generation in silver-treated bronchial epithelial cells prompting evaluation of three antioxidants, N-acetyl cysteine (NAC), ascorbic acid, and melatonin, to identify potential prophylactic agents. Among them, NAC was the only candidate that abrogated the ROS generation in response to silver acetate exposure resulting in the rescue of these cells from silver-associated toxicity. Further, this protective effect directly translated to preservation of metabolic activity, as demonstrated by the normal levels of citric acid cycle metabolites in NAC-pretreated silver acetate-exposed cells. Because the citric acid cycle remained functional, silver-exposed cells pre-incubated with NAC demonstrated significantly higher levels of adenosine triphosphate levels compared with NAC-free controls. Moreover, we found that this prodigious capacity of NAC to rescue silver acetate-exposed cells was due not only to its antioxidant activity, but also to its ability to directly bind silver. Despite binding to silver, NAC did not alter the antimicrobial activity of silver acetate.


Assuntos
Acetilcisteína/farmacologia , Antibacterianos/farmacologia , Depuradores de Radicais Livres/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Prata/farmacologia , Prata/toxicidade , Acetatos/farmacologia , Trifosfato de Adenosina/metabolismo , Ácido Ascórbico/farmacologia , Linhagem Celular , Cromatografia Gasosa-Espectrometria de Massas , Glutationa/metabolismo , Humanos , Melatonina/farmacologia , Testes de Sensibilidade Microbiana , Compostos de Prata/farmacologia , Superóxidos/metabolismo
18.
Life Sci ; 257: 118096, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32679150

RESUMO

AIMS: The molecular pathogenesis of COVID-19 is similar to other coronavirus (CoV) infections viz. severe acute respiratory syndrome (SARS) in human. Due to scarcity of the suitable treatment strategy, the present study was undertaken to explore host protein(s) targeted by potent repurposed drug(s) in COVID-19. MATERIALS AND METHODS: The differentially expressed genes (DEGs) were identified from microarray data repository of SARS-CoV patient blood. The repurposed drugs for COVID-19 were selected from available literature. Using DEGs and drugs, the protein-protein interaction (PPI) and chemo-protein interaction (CPI) networks were constructed and combined to develop an interactome model of PPI-CPI network. The top-ranked sub-network with its hub-bottleneck nodes were evaluated with their functional annotations. KEY FINDINGS: A total of 120 DEGs and 65 drugs were identified. The PPI-CPI network (118 nodes and 293 edges) exhibited a top-ranked sub-network (35 nodes and 174 connectivities) with 12 hub-bottleneck nodes having two drugs chloroquine and melatonin in association with 10 proteins corresponding to six upregulated and four downregulated genes. Two drugs interacted directly with the hub-bottleneck node i.e. matrix metallopeptidase 9 (MMP9), a host protein corresponding to its upregulated gene. MMP9 showed functional annotations associated with neutrophil mediated immunoinflammation. Moreover, literature survey revealed that angiotensin converting enzyme 2, a membrane receptor of SARS-CoV-2 virus, might have functional cooperativity with MMP9 and a possible interaction with both drugs. SIGNIFICANCE: The present study reveals that between chloroquine and melatonin, melatonin appears to be more promising repurposed drug against MMP9 for better immunocompromisation in COVID-19.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/metabolismo , Pneumonia Viral/metabolismo , Mapas de Interação de Proteínas/efeitos dos fármacos , Antivirais/uso terapêutico , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidade , Cloroquina/farmacologia , Biologia Computacional/métodos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Melatonina/farmacologia , Metaloproteases/metabolismo , Pandemias , Peptidil Dipeptidase A , Pneumonia Viral/fisiopatologia , Transporte Proteico
19.
Arch Med Res ; 51(6): 524-534, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32473749

RESUMO

OBJECTIVE: To investigate the effects and molecular mechanism of melatonin (MT) on NF-κB and TGF-ß/Smad3 signaling pathways in db/db diabetic mice. METHODS: db/db diabetic mice were divided into five groups treated with melatonin at doses of 50, 100, 200 µg/kg, the urinary concentration was detected by ELISA, renal histology was observed in PAS paining. Mouse mesangial cells were divided into mannitol control group, normal control group, normal control + MT group, high glucose group, high glucose + different concentrations (10, 100, 1000) µmol/L MT group. The proliferation of mesangial cells was detected by EdU kit; the expression of NF-κBp65, ColⅣ and Fn were detected by laser confocal system; the concentrations and mRNA levels of ColⅣ and Fn were detected by ELISA and qRT-PCR. the expressions of ColⅣ, Fn, IκB, p-IκB, TGF-ß1, Smad3 and p-Smad3 were detected by Western blot in renal tissues and mesangial cells. RESULTS: MT treatment could markedly improve the kidney histopathologic lesions. Compared with the db/m mice, 24 h urinary albumin excretion rate (UAER) and the expressions of ColIV, Fn, p-IκB/IκB, NF-κBp65, TGF-ß1 and p-Smad3/Smad3 were decreased after melatonin treatment (p <0.05). Compared with the control group, the proliferation function of mesangial cells in high glucose group was significantly enhanced, and the expressions of ColIV, Fn, p-IκB/IκB, NF-κBp65, TGF-ß1 and p-Smad3/Smad3 in mesangial cells were significantly up-regulated (p <0.05), and these changes were significantly lowered in MT treatment. CONCLUSION: Melatonin can inhibit renal inflammation and fibrosis by inhibiting the NF-κB and TGF-ß1/Smad3 signaling pathways, and melatonin may be a promising therapeutic target in diabetic nephropathy.


Assuntos
Depressores do Sistema Nervoso Central/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Fibrose/tratamento farmacológico , Rim/patologia , Melatonina/uso terapêutico , NF-kappa B/efeitos dos fármacos , Proteína Smad3/efeitos dos fármacos , Fator de Crescimento Transformador beta1/efeitos dos fármacos , Animais , Depressores do Sistema Nervoso Central/farmacologia , Diabetes Mellitus Experimental , Nefropatias Diabéticas/patologia , Masculino , Melatonina/farmacologia , Camundongos , NF-kappa B/antagonistas & inibidores , Proteína Smad3/antagonistas & inibidores , Fator de Crescimento Transformador beta1/antagonistas & inibidores
20.
Ecotoxicol Environ Saf ; 201: 110853, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32563160

RESUMO

The phytotoxicity caused by 500 µM ZnSO4.7H2O and its detoxifying by co-application of 100 µM of MT melatonin (MT) and glutathione (GSH) in 6-week-old safflower plants have been investigated. Reduced biomass production and total chlorophyll content on the one hand and increased content of hydrogen peroxide (H2O2), malondialdehyde (MDA) with increase in lipoxygenase activity, on the other hand, showed Zn- induced oxidative damage in safflower seedlings. When MT, GSH and especially MT + GSH exogenously were applied to Zn-stressed seedlings, the content of H2O2, MDA and the activity of lipoxygenase considerably decreased. In Zn- treated seedlings, the application of these signaling molecules led to a considerable increment in ascorbate (ASC), GSH and phytochelatin (PC) contents along with the induction of activity of antioxidant enzymes including ascorbate-glutathione cycle enzymes when compared with the plants stressed with Zn only. In Zn-stressed safflower seedlings treated with MT, GSH and MT + GSH, decreased activity of enzymes involved in glyoxalase system may be associated with the role of MT and GSH in reducing Zn uptake and reducing Zn-induced toxicity and subsequently, lower plant's defense responses. The data showed that the effects of MT and GSH, in particular, the combination of these two molecules in reducing Zn uptake and diminishing its accumulation in the shoots of safflower seedlings, and also the participation of MT and GSH on increasing plant ability to tolerate high amount of Zn through stimulation of various antioxidant defense systems suggest them as suitable candidates to better the survival of safflower in soils contaminated with Zn excess.


Assuntos
Antioxidantes/farmacologia , Carthamus tinctorius/efeitos dos fármacos , Glutationa/farmacologia , Melatonina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Poluentes do Solo/toxicidade , Zinco/toxicidade , Ácido Ascórbico/metabolismo , Carthamus tinctorius/crescimento & desenvolvimento , Carthamus tinctorius/metabolismo , Clorofila/metabolismo , Sinergismo Farmacológico , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Oxirredução , Fitoquelatinas/metabolismo , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/metabolismo
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