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1.
Biomed Pharmacother ; 118: 109265, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545282

RESUMO

Kaempferol-3-O-rhamnoside (KOR) has multiple potency involved in anti-cancer, anti-inflammatory and antibacterial actions. However, the potential roles of KOR and the analogues isolated from the leaves of Cyclocarya paliurus in anti-erythroleukemia remain unclear. In the present study, KOR and the two analogues (Kaempferol-3-O-(4″-O-acetyl-a-L-rhamnopyranoside) (KLR) and (kaempferol-3-O-α-L-(4″-E-p-coumaroyl) rhamnoside) (KCR) were isolated from leaves of Cyclocarya paliurus. Cell viability assay showed that KCR exerted an excellent anti-erythroleukemia activity. We observed that KCR not only significantly increased the percentage of G2 phase and apoptotic cells compared with control group, but also induced megakaryocytic differentiation in HEL and K562 cells by flow cytometry, indicating that KCR might inhibit cell proliferation through inducing differentiation-mediated apoptosis and cell cycle arrest. Mechanism investigation revealed that KCR treatment obviously increased phosphorylation levels of PKCδ and ERK1/2 as well as GATA1 expression. Taken together, these findings demonstrate that KCR induces megakaryocytic differentiation and suppresses leukemogenesis at least partly through activation of PKCδ/ERK1/2 signaling pathway in erythroleukemia cells. KCR may also serve as a promising natural compound for human erythroleukemia treatment.


Assuntos
Carcinogênese/patologia , Diferenciação Celular/efeitos dos fármacos , Leucemia/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Megacariócitos/patologia , Proteína Quinase C-delta/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia , Apoptose/efeitos dos fármacos , Carcinogênese/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Glicosídeos/química , Glicosídeos/farmacologia , Glicosídeos/uso terapêutico , Humanos , Concentração Inibidora 50 , Células K562 , Quempferóis/química , Quempferóis/farmacologia , Quempferóis/uso terapêutico , Leucemia/tratamento farmacológico , Megacariócitos/efeitos dos fármacos , Modelos Biológicos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Bibliotecas de Moléculas Pequenas/química
2.
Int J Nanomedicine ; 14: 5147-5157, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371953

RESUMO

Background: Kaempferol (K) is a recognized anticancer drug that can conjugate with small-size gold nanoclusters (AuNCs). Materials and methods: K-AuNCs were synthesized and their use as an anticancer drug was explored using A549 lung cancer cells. Colony formation and cell migration assays were carried out. The morphology of the K-AuNCs treated A549 cells was explored using bio-atomic force microscopy. Results: The K-AuNCs were 1-3 nm in diameter and emitted strong fluorescent at 650 nm following excitation at 550 nm. The stretching and bending nature of the K-AuNCs were analyzed by the Fourier transform infrared spectroscopy. The presence of kaempferol in the AuNCs were confirmed by the PL spectroscopy. Conclusion: The synthesized K-AuNCs mainly targeted and damaged the nuclei of the cancer cells. This composite nanocluster was less toxicity to the normal human cell and higher toxicity to the A549 lunch cancer cell and these material is potential for anticancer drug delivery and bio imaging applications.


Assuntos
Antineoplásicos/uso terapêutico , Ouro/química , Quempferóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas Metálicas/química , Células A549 , Antineoplásicos/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/patologia , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Humanos , Quempferóis/farmacologia , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/ultraestrutura , Fenômenos Ópticos , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
3.
Artif Cells Nanomed Biotechnol ; 47(1): 3614-3620, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31468982

RESUMO

Osteoarthritis (OA) is one of the most characterized joint diseases associated with chondrocyte apoptosis. Juglanin has been reported to have anti-inflammation activity. This study aimed to evaluate the protective anti-inflammatory effects of juglanin in human OA chondrocytes. Human OA chondrocytes were pretreated with juglanin (10, 20 and 40 µM) for 2 h and subsequently stimulated with IL-1ß for 24 h. Nitric oxide (NO) production was determined using the Griess method and prostaglandin E2 (PGE2), matrix metalloproteinase-3, -9 and -13 (MMP-3, MMP-9 and MMP-13), TNF-α, and IL-6 were assessed using ELISA. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-4 and -5 (ADAMTS-4 and ADAMTS-5) were detected by qRT-PCR and western blot analysis. NF-κB signalling molecules were detected by western blot analysis. The results showed that juglanin dose-dependently suppressed PGE2, NO, MMP-1, MMP3, MMP13, TNF-α and IL-6 production induced by IL-1ß. The expression of COX-2, iNOS, ADAMTS-4 and ADAMTS-5 induced by IL-1ß were also suppressed by juglanin pretreatment. Western blot analysis showed that juglanin suppressed IL-1ß-induced NF-κB activation. Taken together, we found that juglanin inhibits IL-1ß-induced inflammation through the regulation of NF-κB signalling. Juglanin might be used as a therapeutic agent for treating OA.


Assuntos
Anti-Inflamatórios/farmacologia , Condrócitos/efeitos dos fármacos , Glicosídeos/farmacologia , Interleucina-1beta/efeitos adversos , Quempferóis/farmacologia , Proteína ADAMTS4/genética , Proteína ADAMTS4/metabolismo , Proteína ADAMTS5/genética , Proteína ADAMTS5/metabolismo , Anti-Inflamatórios/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Dinoprostona/biossíntese , Relação Dose-Resposta a Droga , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glicosídeos/uso terapêutico , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Interleucina-6/biossíntese , Quempferóis/uso terapêutico , Metaloproteinases da Matriz/biossíntese , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Fator de Necrose Tumoral alfa/biossíntese
4.
Biomed Pharmacother ; 117: 109086, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31200254

RESUMO

In the last century, natural compounds have achieved remarkable achievements in the treatment of tumors through chemotherapy. This inspired scientists to continuously explore anticancer agents from natural compounds. Kaempferol is an ordinary natural compound, the most common flavonoid, which is widely existed in vegetables and fruits. It has been reported to have various anticancer activities, including breast cancer, prostate cancer, bladder cancer, cervical cancer, colon cancer, liver cancer, lung cancer, ovarian cancer, leukemia, etc. Meanwhile, we found that there were more reports on breast cancer among these cancers although there are limited clinical studies that have addressed the benefits of kaempferol as an anti-cancer agent for breast cancer treatment. Then we realize that although kaempferol has been reported to have anti-breast cancer effect many times, it is still far from becoming a real anti-breast cancer agent. Therefore, in this review, we talk about the options for improving the anti-breast cancer effect of kaempferol, including various techniques and methods to improve the bioavailability of kaempferol, the idea of combining other compounds to produce synergistic effects, and the possibility of developing kaempferol into a targeted drug delivery system.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quempferóis/farmacologia , Quempferóis/uso terapêutico , Animais , Sistemas de Liberação de Medicamentos/métodos , Feminino , Humanos
5.
Drug Dev Res ; 80(3): 294-309, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30864233

RESUMO

This study was designed to delineate the effect of kaempferol (KF) on heart failure (HF) in diabetic rats. Streptozotocin-induced male diabetic rats received KF orally at 10 and 20 mg/kg for 42 consecutive days. In last 2 days of the experimental period, isoproterenol was subcutaneously injected at 85 mg/kg to induce HF. The hearts were processed for hemodynamic, biochemical, molecular, and histological investigations. Systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were elevated in KF-treated HF-induced diabetic rats. Moreover, KF treatment resulted in decreased fasting blood glucose and glycosylated hemoglobin levels with increased serum insulin levels. Besides, serum cardiac injury markers like troponin-I, creatine kinase-muscle/brain, lactate dehydrogenase, and brain natriuretic peptide levels were significantly reduced in KF treatment. KF treatment has shown decrease in cardiac heme oxygenase-1, nuclear factor erythroid 2-related factor 2 (Nrf-2), and γ-glutamylcysteine synthetase with increased Keap1 mRNA levels. The cardioprotection of KF was improved by inhibition of apoptosis via blocking phosphorylation of Akt/glycogen synthase kinase (GSK)-3ß and p38 mitogen-activated protein-kinase/extracellular signal-regulated kinases signaling pathways in HF-induced diabetic rats. Moreover, reduced cardiac apoptosis in KF treatment was confirmed by decreased terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) positive cells, histopathological changes in HF-induced diabetic rats. Therefore, the cardioprotective effect of KF is attributed to the regulation of Nrf2, nuclear factor kappa-light-chain-enhancer of activated B cells, and Akt/GSK-3ß signaling pathways in HF-induced diabetic rats.


Assuntos
Cardiotônicos/farmacologia , Diabetes Mellitus Experimental/metabolismo , Insuficiência Cardíaca/metabolismo , Quempferóis/farmacologia , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Animais , Cardiotônicos/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Glicogênio Sintase Quinase 3 beta/metabolismo , Coração/efeitos dos fármacos , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/tratamento farmacológico , Isoproterenol , Quempferóis/uso terapêutico , Masculino , Infarto do Miocárdio/tratamento farmacológico , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
6.
Phytother Res ; 33(4): 1065-1073, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30701598

RESUMO

Kaempferide (KF) is a compound of flavonoids from Alpinae oxyphylla Miq, and the herb itself is used as a classical tonic agent. This paper aims to investigate the effects of KF on cognitive function impairment and neurodegeneration in the mouse model of Alzheimer's disease induced by intracerebroventricular (ICV) injection of Aß1-42 . The mice were treated with KF at doses of 0.02 and 0.2 mg/kg/day (ICV) for five consecutive days after Aß1-42 exposures. The behavioral test results showed that KF could prevent cognitive decline in mice induced by Aß1-42 as assessed by the locomotor activity test, Y-maze test, and Morris water maze test. Furthermore, the activities of superoxide dismutase and malondialdehyde in the hippocampus and cerebral cortex were elevated by KF administration. Results of hippocampus slices showed that neurons were integrated and regularly arranged in the groups, which were administered along with KF. In addition, we found KF could boost brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/cAMP response element-binding (CREB) protein signal in the hippocampus. All results illustrated that KF could exert neuroprotective effects at least partly through alleviating oxidative stress and enhancing the BDNF/TrkB/CREB pathway in Aß1-42 -induced mice.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Quempferóis/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Tropomiosina/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Humanos , Quempferóis/farmacologia , Masculino , Camundongos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Transdução de Sinais
7.
Phytother Res ; 33(2): 263-275, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30402931

RESUMO

Kaempferol, a natural flavonoid present in several plants, possesses a wide range of therapeutic properties such as antioxidant, anticancer, and anti-inflammatory. It has a significant role in reducing cancer and can act as a therapeutic agent in the treatment of diseases and ailments such as diabetes, obesity, cardiovascular diseases, oxidative stress, asthma, and microbial contamination disorders. Kaempferol acts through different mechanisms: It induces apoptosis (HeLa cervical cancer cells), decreases cell viability (G2/M phase), downregulates phosphoinositide 3-kinase (PI3K)/AKT (protein kinase B) and human T-cell leukemia/lymphoma virus-I (HTLV-I) signaling pathways, suppresses protein expression of epithelial-mesenchymal transition (EMT)-related markers including N-cadherin, E-cadherin, Slug, and Snail, and metastasis-related markers such as matrix metallopeptidase 2 (MMP-2). Accordingly, the aim of the present review is to collect information pertaining to the effective role of kaempferol against various degenerative disorders, summarize the antioxidant, anti-inflammatory, anticancer, antidiabetic, and antiaging effects of kaempferol and to review the progress of recent research and available data on kaempferol as a protective and chemotherapeutic agent against several ailments.


Assuntos
Quimioprevenção/métodos , Quempferóis/farmacologia , Quempferóis/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Suplementos Nutricionais , Regulação para Baixo/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Células HeLa , Humanos , Transdução de Sinais/efeitos dos fármacos
8.
Biomed Pharmacother ; 110: 561-570, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30537673

RESUMO

Spermatogenic dysfunction is a common complication in men with diabetes and is the most important manifestation of diabetes-related male reproduction damage. Astragalin (AG) is one of the main flavonoids from Cuscuta chinensis, which has rich pharmacological activities. This study aimed to establish whether AG may contribute to the recovery from spermatogenic dysfunction. AG (3.3, 10 and 30 mg/kg) and Clomiphene (5 mg/kg) were orally administered to streptozotocin-induced diabetic male mice for 8 weeks. After the experiments performed, reproductive organs, sperm parameters and histomorphological changes were analysed. Antioxidant and anti-inflammatory capacity were estimated in testicular tissues. The results revealed that AG significantly improved the reproductive organs, sperm parameters and testicular morphology to different degrees in diabetic mice. Nitric oxide (NO) and malondialdehyde (MDA) levels were significantly reduced, and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), markedly increased in the testicular tissue after AG was administered. Interestingly, AG also downregulated the protein expressions of tumour necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) in testes. In conclusion, AG is a potential beneficial agent to protect diabetic-induced spermatogenic dysfunction in male mice by increasing antioxidant enzymes activities and inhibiting inflammation.


Assuntos
Antioxidantes/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Mediadores da Inflamação/metabolismo , Quempferóis/uso terapêutico , Espermatogênese/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mediadores da Inflamação/antagonistas & inibidores , Quempferóis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Distribuição Aleatória , Espermatogênese/fisiologia , Resultado do Tratamento
9.
Biomed Pharmacother ; 111: 468-475, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30594786

RESUMO

Kaempferol is a flavonoid compound that has many functions, such as anti-inflammation and antioxidation. Acute liver failure (ALF) is a life-threatening illness accompanied by serious inflammation and extensive hepatocyte apoptosis. The aim of this study was to examine the therapeutic potential of kaempferol and its mechanism in ALF. In a murine ALF model induced by d-galactosamine (d-GalN, 700 mg/kg) / lipopolysaccharide (LPS, 10 µg/kg), mice were pretreated with kaempferol at 2 h before d-GalN/LPS administration and then sacrificed 6 h after d-GalN/LPS injection. Lethality, liver damage, endoplasmic reticulum(ER) stress, hepatocyte viability and apoptosis were evaluated. Whether pretreatment of kaempferol protected hepatocytes from ER stress-induced apoptosis was detected in vitro. Pretreatment of kaempferol decreased lethality, prolonged the survival time and significantly protected against liver injury, which was indicated by decreased transaminase levels and the well-preserved liver structure. The protective effect of kaempferol on the ALF mouse model was achieved by inhibiting hepatocyte apoptosis. Moreover, pretreatment of kaempferol increased the expression of glucose-regulated/binding immunoglobulin protein 78 (Grp78), decreased the expression of C/EBP-homologous protein (CHOP), and protected hepatocytes from ER stress-induced apoptosis in vitro. Our results showed that pretreatment of Grp78 siRNA partially negated the hepatic protection from kaempferol and reversed the inhibition of CHOP protein expression in d-GalN/LPS-induced ALF mice. In conclusion, kaempferol inhibits hepatocyte apoptosis to protect mice from liver failure by regulating the ER stress-Grp78-CHOP signaling pathway. Therefore, kaempferol may be used to treat ALF.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Galactosamina/toxicidade , Proteínas de Choque Térmico/biossíntese , Quempferóis/uso terapêutico , Falência Hepática Aguda/metabolismo , Fator de Transcrição CHOP/biossíntese , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Células Cultivadas , Estresse do Retículo Endoplasmático/fisiologia , Proteínas de Choque Térmico/agonistas , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Quempferóis/farmacologia , Lipopolissacarídeos/toxicidade , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Fator de Transcrição CHOP/antagonistas & inibidores
10.
Biomed Pharmacother ; 109: 1610-1619, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551415

RESUMO

RhoA/Rho-associated coiled-coil forming protein serine/threonine kinase (ROCK) has appeared as a potential therapeutic target in numerous diseases, because of its preventing action on various enzymes providing antioxidant and cytoprotective action. Progression and pathophysiology of diabetic nephropathy have also shown potential involvement of oxidative stress and inflammatory pathways. In the present study, we investigated the effect of kaempferol on hyperglycemia-induced activation of RhoA kinase and associated inflammatory signaling cascade. Currently there is only small literature available on the mechanism of anti-diabetic and nephroprotective action of this compound, which creates a void. Therefore, we focused here on the investigation of molecular mechanisms for kaempferol by means of in vitro testing, using rat (NRK-52E) and human renal tubular epithelial cells (RPTEC). Our findings suggest that kaempferol inhibits hyperglycemia-induced activation of RhoA and decreased oxidative stress, pro-inflammatory cytokines (TNF-α and IL-1ß) and fibrosis (TGF-ß1 expression, extracellular matrix protein expression) in NRK-52E and RPTEC cells. Therefore, kaempferol can be used as a potential therapeutic for the treatment of diabetic nephropathy.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Mediadores da Inflamação/metabolismo , Quempferóis/uso terapêutico , Proteínas rho de Ligação ao GTP/metabolismo , Quinases Associadas a rho/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Nefropatias Diabéticas/patologia , Relação Dose-Resposta a Droga , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Quempferóis/farmacologia , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Proteínas rho de Ligação ao GTP/antagonistas & inibidores , Quinases Associadas a rho/antagonistas & inibidores
11.
Oxid Med Cell Longev ; 2018: 1610751, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30584457

RESUMO

The protection of retinal pigment epithelium (RPE) injury plays an important role in the prevention of or in delaying the pathological progress of retinal degeneration diseases, like age-related macular degeneration (AMD), diabetic retinopathy, and retinitis pigmentosa. Oxidative stress has been identified as a major inducer of RPE injury, which eventually could lead to a loss of vision. Kaempferol is a natural flavonoid widely distributed in many edible plants, fruits, and traditional medicines and has been reported to have antioxidant, anti-inflammatory, anticancer, and antimicrobial activities. The present study demonstrates that the total antioxidant capacity of kaempferol is approximately two times stronger than that of lutein which is also a natural antioxidant that is widely used in the prevention or treatment of AMD. Our data indicates that kaempferol protects human RPE cells (ARPE-19) from hydrogen peroxide- (H2O2-) induced oxidative cell damage and apoptosis through the signaling pathways involving Bax/Bcl-2 and caspase-3 molecules proofed by real-time PCR and Western blot results. Kaempferol also inhibits the upregulated vascular endothelial growth factor (VEGF) mRNA expression levels induced by H2O2 in ARPE-19 cells and affects the oxidation and antioxidant imbalanced system in ARPE-19 cells treated by H2O2 through the regulations of both the activities of reactive oxygen species (ROS) and superoxide dismutase (SOD). Furthermore, our in vivo experimental results show that in sodium iodate-induced retinal degeneration rat model, kaempferol could protect sodium iodate-induced pathological changes of retina tissue and retinal cells apoptosis as well as the upregulated VEGF protein expression in RPE cells. In summary, these novel findings demonstrate that kaempferol could protect oxidative stressed-human RPE cell damage through its antioxidant activity and antiapoptosis function, suggesting that kaempferol has a potential role in the prevention and therapeutic treatment of AMD or other retinal diseases mediated by oxidative stress.


Assuntos
Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Quempferóis/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Doenças Retinianas/tratamento farmacológico , Doenças Retinianas/metabolismo , Epitélio Pigmentado da Retina/citologia , Animais , Humanos , Peróxido de Hidrogênio/farmacologia , Degeneração Macular/tratamento farmacológico , Degeneração Macular/metabolismo , RNA Mensageiro/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética
12.
Pestic Biochem Physiol ; 152: 29-37, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30497708

RESUMO

Chlorpyrifos (CPF) is an agricultural pesticide and a potential food contaminant, which causes neurotoxicity. Here, we aimed at exploring the link between the repeated exposure to CPF and memory dysfunction in rats and the possible protective effect of kaempferol, a flavonoid with appreciable antioxidant and anti-inflammatory activities. Rats were divided into: Control group (received drug vehicles for 14 days); CPF-treated group (received subcutaneous 18 mg/kg BW of CPF daily for 14 days and CPF + Kaempferol treated group (received the same CPF dose +21 mg/kg BW of Kaempferol intraperitoneally for 14 days. On the 14th day, Y-maze and novel target recognition behavioral tests were employed to evaluate memory deficits. 24 h after the last dose of CPF, animals were sacrificed, and brain tissues were used for the determination of oxidative stress biomarkers and gene expression levels of GSK3ß and Nrf2. The results revealed that CPF-treated rats suffered from severe deterioration of spatial and non-spatial memory functions with low activities of antioxidant enzymes and acetylcholinesterase (AChE). The administration of kaempferol significantly protected against CPF-induced neuronal damage, increased the activities of antioxidant enzymes and AChE and induced a better performance in the behavioral tests. The protective effect of kaempferol was mediated through the inhibition of GSK3ß gene expression and the induction of Nrf2 expression in the brain tissues. In conclusion, the repeated exposure to CPF is associated with oxidative stress and memory deficits in rats. However, kaempferol administration effectively alleviated CPF- induced brain toxicity, possibly through the modulation of GSK3ß-Nrf2 signaling pathway.


Assuntos
Glicogênio Sintase Quinase 3 beta/metabolismo , Quempferóis/uso terapêutico , Transtornos da Memória/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Acetilcolinesterase/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Clorpirifos , Quempferóis/farmacologia , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
13.
Iran J Allergy Asthma Immunol ; 17(5): 428-435, 2018 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-30518185

RESUMO

Kaempferol, a phytochemical found in many edible plants, is known to alleviate diseases such as cancer, allergy, and inflammation. The objective of this study was to investigate whether kaempferol could reduce omega-6 and ovalbumin-mediated allergic reactions at lung and trachea in BALB/c mice. Mice were allocated into five groups: 1) control group (CON); 2) positive control group with orally administration of omega-6 (POS); 3) bovine serum albumin (BSA) sensitization group (with BSA injection and ovalbumin inhalation); 4) BSA+K10 group: BSA injection, 10 µg/g of kaempferol administration and ovalbumin inhalation; and 5) BSA+K20 group: BSA injection, 20 µg/g of kaempferol administration and ovalbumin inhalation. Results revealed that serum histamine level was the highest (p<0.01) in BSA group. In lung tissue and trachea, cyclooxygenase 2 (Cox2) expression was significantly (p<0.05) higher in the BSA group compared to that in other groups. However, phosphorylated cytosolic phospholipase A2 (p-cPLA2) expression in the trachea was not significantly different among groups. Taken together, results of this study suggest that kaempferol might be useful for alleviating inflammation reaction associated with Cox2 expression. However, the exact mechanism of action involved in the effect of kaempferol on inflammatory response remains unclear.


Assuntos
Anti-Inflamatórios/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Hipersensibilidade/tratamento farmacológico , Quempferóis/uso terapêutico , Pulmão/metabolismo , Pneumonia/tratamento farmacológico , Traqueia/metabolismo , Animais , Modelos Animais de Doenças , Ácidos Graxos Ômega-6/administração & dosagem , Humanos , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Fosfolipases A2 Citosólicas/metabolismo , Traqueia/patologia
14.
J Ethnopharmacol ; 226: 82-89, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30107246

RESUMO

ETHOPHARMACOLOGICAL RELEVANCE: The propolis is extensively used in folk medicine in natura or to prepare pharmaceutical formulations since ancient time to improve health or prevent diseases, among them gastrointestinal disorders. Aiming to contribute in the scientific validation about the popular use of Brazilian Green propolis (BGP) against gastritis and gastric ulcer, this work evaluated the antiulcer potential of isolated compounds from BGP, three prenylated p-coumaric acid derivatives and two flavonoids, respectively named: 3,5 diprenyl-4-hydroxycinnamic acid (artepillin C) (1), 3-prenyl-4-dihydroxycinnamoiloxy cinnamic acid (baccharin) (2), 3-prenyl-4-hydroxycinnamic acid (drupanin) (3), aromadendrin-4'-O-methyl-ether (4) and kaempferide (5). MATERIAL AND METHODS: The compounds were characterized by nuclear magnetic resonance and mass spectrometry. Their gastroprotective effects were evaluated against ethanol/HCl- and indomethacin-induced ulcer in mice. Further, histological, histochemical, oxidative and inflammatory parameters were analyzed at ulcerated tissue. Acid antisecretory activities also were also assessed. RESULTS: Compound 2 did not reduce the ethanol/HCl- induced ulcer at 30 mg/kg (p.o), whereas the minimum oral gastroprotective doses of 1, 3, 4 and 5 were 0.3, 0.3, 3 and 3 mg/kg, respectively. Besides, these compounds prevented ethanol/HCl-induced ulcer by intraperitoneal route, as well as indomethacin-induced ulcer by oral route. The gastroprotection was accompanied by normalization of superoxide dismutase, catalase and glutathione-S-transferase activities and reduction in myeloperoxidase activity. Moreover, the compounds 4 and 5 increased the gastric mucin content and 1 reduced TNF amount. Furthermore, 1, 3, 4 and 5 decreased volume, pH, total acidity and pepsin activity of the gastric juice from rats. CONCLUSIONS: Together, our findings showed a diversified mode of action elicited by 1, 3, 4 and 5 on the gastroprotection and contribute to explain the anti-ulcer activity reported for BGP.


Assuntos
Antiulcerosos/uso terapêutico , Própole/química , Úlcera Gástrica/tratamento farmacológico , Animais , Cinamatos/uso terapêutico , Etanol , Flavonoides/uso terapêutico , Ácido Clorídrico , Indometacina , Quempferóis/uso terapêutico , Masculino , Camundongos , Fenilpropionatos/uso terapêutico , Própole/uso terapêutico , Úlcera Gástrica/induzido quimicamente
15.
Int J Mol Sci ; 19(6)2018 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-29925776

RESUMO

The term orthodisease defines human disorders in which the pathogenic gene has orthologs in model organism genomes. Yeasts have been instrumental for gaining insights into the molecular basis of many human disorders, particularly those resulting from impaired cellular metabolism. We and others have used yeasts as a model system to study the molecular basis of Hailey-Hailey disease (HHD), a human blistering skin disorder caused by haploinsufficiency of the gene ATP2C1 the orthologous of the yeast gene PMR1. We observed that K. lactis cells defective for PMR1 gene share several biological similarities with HHD derived keratinocytes. Based on the conservation of ATP2C1/PMR1 function from yeast to human, here we used a yeast-based assay to screen for molecules able to influence the pleiotropy associated with PMR1 deletion. We identified six compounds, Kaempferol, Indirubin, Lappaconite, Cyclocytidine, Azomycin and Nalidixic Acid that induced different major shape phenotypes in K. lactis. These include mitochondrial and the cell-wall morphology-related phenotypes. Interestingly, a secondary assay in mammalian cells confirmed activity for Kaempferol. Indeed, this compound was also active on human keratinocytes depleted of ATP2C1 function by siRNA-treatment used as an in-vitro model of HHD. We found that Kaempferol was a potent NRF2 regulator, strongly inducing its expression and its downstream target NQO1. In addition, Kaempferol could decrease oxidative stress of ATP2C1 defective keratinocytes, characterized by reduced NRF2-expression. Our results indicated that the activation of these pathways might provide protection to the HHD-skin cells. As oxidative stress plays pivotal roles in promoting the skin lesions of Hailey-Hailey, the NRF2 pathway could be a viable therapeutic target for HHD.


Assuntos
Produtos Biológicos/farmacologia , Quempferóis/farmacologia , Kluyveromyces/efeitos dos fármacos , Pênfigo Familiar Benigno/terapia , Produtos Biológicos/uso terapêutico , Cálcio/metabolismo , ATPases Transportadoras de Cálcio/genética , Linhagem Celular , Parede Celular/efeitos dos fármacos , Proteínas Fúngicas/genética , Pleiotropia Genética , Humanos , Quempferóis/uso terapêutico , Queratinócitos/efeitos dos fármacos , Kluyveromyces/genética , Mitocôndrias/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pênfigo Familiar Benigno/genética , Cultura Primária de Células
16.
CNS Neurol Disord Drug Targets ; 17(6): 421-429, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29745345

RESUMO

BACKGROUND: Alzheimer's disease (AD) is characterized by the accumulation and deposition of ß-amyloid peptides leading to a progressive neuronal damage and cell loss. Besides several hypotheses for explaining the neurodegenerative mechanisms, oxidative stress has been considered to be one of them. Till date, there is no cure for AD, but the pathogenesis of the disease could be delayed by the use of natural antioxidants. In this context, we decided to study the effect of kaempferol against the transgenic Drosophila expressing human amyloid beta-42. METHOD: The AD flies were allowed to feed on the diet having 10, 20, 30 and 40µM of kaempferol for 30 days. After 30 days of exposure, the amyloid beta flies were studied for their climbing ability and Aversive Phototaxis Suppression assay. Amyloid beta flies head homogenate was prepared for estimating the oxidative stress markers, Caspase and acetylcholinesterase activity. RESULTS: The results of the present study reveal that the exposure of AD flies to kaempferol delayed the loss of climbing ability, memory, reduced the oxidative stress and acetylcholinesterase activity. CONCLUSION: Kaempferol could be used as a possible therapeutic agent against the progression of the Alzheimer's disease.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antipsicóticos/uso terapêutico , Quempferóis/uso terapêutico , Acetilcolinesterase/metabolismo , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Animais Geneticamente Modificados , Caspases/metabolismo , Modelos Animais de Doenças , Drosophila , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/genética , Fragmentos de Peptídeos/metabolismo , Fototaxia/efeitos dos fármacos , Carbonilação Proteica/efeitos dos fármacos , Carbonilação Proteica/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
17.
Chem Biodivers ; 15(8): e1800129, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29802806

RESUMO

Elaeagnus pungens leaf was documented to be very effective to treat asthma and chronic bronchitis both as traditional Chinese medicine and minority traditional medicine; yet the actual effective components still remain unknown. This work is to investigate the anti-inflammatory, antalgic and antitussive activities of E. pungens leaf, quercetin and kaempferol, and their contents in E. pungens leaf. Pharmacological experiments showed that they could considerably reduce ear-swelling of mouse and relieve writhing reaction of mouse; they could also prevent mouse from coughing significantly. These findings suggested that quercetin and kaempferol are major effective components treating asthma and chronic bronchitis. Quantitative analysis results indicated that the levels of quercetin, kaempferol and isorhamnetin varied greatly in different species of Elaeagnus and in different plant parts: E. pungens leaf is more similar to Elaeagnus umbellate leaf chemically; quercetin level is exceptionally high in Elaeagnus oldhami leaf; E. pungens leaf is a better medical part for treating asthma and chronic bronchitis in comparison with other parts.


Assuntos
Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Bronquite Crônica/tratamento farmacológico , Elaeagnaceae/química , Quempferóis/uso terapêutico , Folhas de Planta/química , Quercetina/análogos & derivados , Quercetina/uso terapêutico , Ácido Acético , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Asma/induzido quimicamente , Bronquite Crônica/induzido quimicamente , Quempferóis/química , Quempferóis/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos , Quercetina/química , Quercetina/isolamento & purificação
18.
Int J Mol Med ; 42(1): 41-52, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29620254

RESUMO

Ultraviolet (UV) radiation induces skin injury, and is associated with the development and formation of melanoma, which is a highly lethal form of skin cancer. Juglanin is a natural product, which is predominantly extracted from Polygonum aviculare, and is considered a functional component among its various compounds. Juglanin has been reported to exert marked protective effects in various diseases via the inhibition of inflammation and tumor cell growth. The present study aimed to explore the effects of juglanin on human skin cancer induced by UV and to reveal the underlying molecular mechanism. In the present study, immunohistochemical analysis, western blot analysis, RT-qPCR analysis and flow cytometry assays were mainly used in vivo and/or in vitro. The results indicated that in mice, UVB exposure increased susceptibility to carcinogens, and accelerated disease pathogenesis. Conversely, juglanin was able to ameliorate this condition via inhibition of inflammation, suppression of cell proliferation and induction of apoptosis via p38/c­Jun N­terminal kinase (JNK) blockage, nuclear factor (NF)­κB inactivation and caspase stimulation in vivo. In addition, in vitro, the present study demonstrated that treatment of UVB­stimulated B16F10 melanoma cells with juglanin resulted in a dose­dependent decrease in cell viability, as well as increased apoptosis via the upregulation of caspase expression and poly (ADP­ribose) polymerase cleavage. In addition, juglanin markedly attenuated p38/JNK signaling, inactivated the phosphoinositide 3­kinase/protein kinase B pathway and suppressed UVB­induced NF­κB activation. Taken together, these results indicated the possibility of applying juglanin in combination with UVB as a potential therapeutic strategy for preventing skin cancer.


Assuntos
Anti-Inflamatórios/uso terapêutico , Apoptose , Carcinogênese/efeitos da radiação , Glicosídeos/uso terapêutico , Quempferóis/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Raios Ultravioleta , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Carcinogênese/efeitos dos fármacos , Caspases/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/efeitos da radiação , Glicosídeos/farmacologia , Humanos , Inflamação/patologia , Quempferóis/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos da radiação , Masculino , Melanoma Experimental/patologia , Camundongos , Poli(ADP-Ribose) Polimerases/metabolismo
20.
Int Immunopharmacol ; 57: 62-71, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29475097

RESUMO

Kaempferol-3-O-ß-d-glucuronide (K3G) having various pharmacological effects was explored for its anti-inflammatory effect in LPS induced RAW 264.7 cells and mice model. K3G significantly inhibited various pro-inflammatory mediators like IL-1ß, NO, PGE2, and LTB4. It upregulated the secretion of anti-inflammatory cytokine IL-10. K3G is found to reduce inflammation when studied for parameters like phagocytic index, carrageenan induced paw edema in mice and organ weight. It reduced inflammation in a dose dependent manner both in-vitro and in-vivo. Further molecular insights into the study reveal that K3G blocks the phosphorylation of NF-kB which is key regulator of inflammation, thereby exhibiting anti-inflammatory potential. Hence, this study permits further investigation to develop K3G as anti-inflammatory drug.


Assuntos
Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Glucuronatos/uso terapêutico , Quempferóis/uso terapêutico , Macrófagos/fisiologia , Animais , Carragenina , Dinoprostona/metabolismo , Edema/induzido quimicamente , Feminino , Glucuronatos/química , Humanos , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Quempferóis/química , Leucotrieno B4/metabolismo , Lipopolissacarídeos/imunologia , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Células RAW 264.7 , Transdução de Sinais , Regulação para Cima
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