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1.
Heliyon ; 10(10): e30835, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38770307

RESUMO

Periodontal disease represents a condition that exhibits substantial global morbidity, and is characterized by the infection and inflammation of the periodontal tissue effectuated by bacterial pathogens. The present study aimed at evaluating the therapeutic efficacy of BenTooth, an edible natural product mixture comprising burdock root extract, persimmon leaf extract and quercetin, against periodontitis both in vitro and in vivo. BenTooth was examined for antimicrobial properties and its impact on cellular responses related to inflammation and bone resorption. Its effects were also assessed in a rat model of ligature-induced periodontitis. BenTooth demonstrated potent antimicrobial activity against P. gingivalis and S. mutans. In RAW264.7 cells, it notably diminished the expression of inducible nitric oxide synthase and cyclooxygenase-2, as well as reduced interleukin-6 and tumor necrosis factor-α levels triggered by P. gingivalis-derived lipopolysaccharide. Furthermore, BenTooth inhibited osteoclastogenesis mediated by the receptor activator of nuclear factor κB ligand. In the rat model, BenTooth consumption mitigated the ligature-induced expansion in distance between the cementoenamel junction and the alveolar bone crest and bolstered the bone volume fraction. These results present BenTooth as a potential therapeutic candidate for the prevention and remediation of periodontal diseases.

2.
Cell Death Dis ; 11(5): 403, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32467587

RESUMO

Methylglyoxal (MGO)-induced cellular apoptosis, oxidative stress, inflammation, and AGE formation are specific events that induce vascular endothelial cell (EC) toxicity in endothelial dysfunction (ED). MGO accumulates quickly in various tissues and plays a prominent role in the pathogeneses of several diabetic complications. Unbalanced angiogenesis is a gateway to the development of diabetic complications. EC apoptosis and autophagy work together to regulate angiogenesis by interacting with different angiogenic factors. In addition to understanding the deep mechanism regarding MGO-dependent autophagy/apoptosis may provide new therapeutic applications to treat diabetes and diabetic complications. Therefore, the present study aimed to investigate the regulatory effects of MGO-induced autophagy and apoptosis on angiogenesis in HAoEC and to elucidate the molecular mechanisms to discover new target base therapy for diabetes and diabetic complications. In MGO-stimulated HAoEC, protein expression was identified using a western blot, autophagosomes were observed by bio-transmission electron microscopy (TEM), and cell autophagic vacuoles and flux were measured using a confocal microscope. We found that MGO significantly induced autophagy, declined the pro-angiogenic effect, decreased proliferation, migration, and formation of tube-like structures, and increased autophagic vacuoles, flux and autophagosomes in the HAoEC in a dose-dependent manner. We observed that MGO-induced autophagic cell death and inhibited the ROS-mediated Akt/mTOR signaling pathway. MGO also triggered apoptosis by elevating the cleaved caspase-3 to Bax/Bcl-2 ratio and through activation of the ROS-mediated MAPKs (p-JNK, p-p38, and p-ERK) signaling pathway. Collectively, these findings suggest that autophagy and apoptosis inhibit angiogenesis via the ROS-mediated Akt/mTOR and MAPKs signaling pathways, respectively, when HAoEC are treated with MGO.


Assuntos
Aorta/patologia , Células Endoteliais/patologia , Aldeído Pirúvico/toxicidade , Apoptose/efeitos dos fármacos , Autofagossomos/efeitos dos fármacos , Autofagossomos/metabolismo , Autofagossomos/ultraestrutura , Autofagia/efeitos dos fármacos , Caspase 3/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Proteínas do Citoesqueleto/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/ultraestrutura , Guanidinas/farmacologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Associadas aos Microtúbulos/metabolismo , Modelos Biológicos , Neovascularização Fisiológica/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Vacúolos/efeitos dos fármacos , Vacúolos/metabolismo , Proteína X Associada a bcl-2/metabolismo
3.
Phytomedicine ; 48: 1-9, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30195866

RESUMO

BACKGROUND: Lespedeza cuneata G.Don (LCE), which belongs to the genus Lespedeza (Leguminosae), is a traditional oriental medicine known to prevent diabetes and cardiovascular diseases. However, no scientific studies about the effectiveness of LCE, their responsible bioactive constituents, and its mechanisms against endothelial dysfunction have been performed. PURPOSE: This study was performed to investigate the role of LCE and its chemical components in ameliorating endothelial dysfunction. METHODS: The production of nitric oxide (NO) was evaluated after LCE treatment in HUVECs. Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent. Western blot analysis was performed to determine the protein expression of endothelial nitric oxide synthase (eNOS) and protein kinase B (PKB, also known as Akt) in human umbilical vein endothelial cells (HUVECs). RESULTS: Pretreatment with L-NAME and LY294002 significantly decreased the LCE-induced NO production, as well as eNOS and Akt phosphorylation. ß-Sitosterol and ß-Sitosterol 6'-linolenoyl-3-O-ß-D-glucopyranoside are the bioactive constituents increase NO production as well as eNOS phosphorylation. CONCLUSION: Our findings suggest that LCE increase NO production via eNOS phosphorylation of PI3K/Akt signaling pathway.


Assuntos
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Lespedeza/química , Óxido Nítrico Sintase Tipo III/metabolismo , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromonas , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Morfolinas , NG-Nitroarginina Metil Éster , Óxido Nítrico/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Doenças Vasculares/metabolismo
4.
Antiviral Res ; 144: 266-272, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28668556

RESUMO

The aim of this study was to establish the effect of a 70% ethanol extract of Elaeocarpus sylvestris (ESE) on varicella-zoster virus (VZV) replication and identify the specific bioactive component(s) underlying its activity. ESE induced a significant reduction in replication of the clinical strain of VZV. Activity-guided fractionation indicated that the ethyl acetate (EtOAc) fraction of ESE contains the active compound(s) inhibiting VZV replication. High-Performance Liquid Chromatography coupled to Electrospray Ionization Quadrupole Time-of-Flight Mass Spectrometry (HPLC-Q-TOF-MS/MS) analysis of the EtOAc fraction of ESE facilitated the identification of 13 chemical components. Among these, 1,2,3,4,6-penta-O-galloyl-ß-D-glucose (PGG) markedly suppressed VZV-induced c-Jun N-terminal kinase (JNK) activation, expression of viral immediate-early 62 (IE62) protein and VZV replication. Our results collectively support the utility of PGG as a potential candidate anti-viral drug to treat VZV-associated diseases.


Assuntos
Elaeocarpaceae/química , Herpesvirus Humano 3/efeitos dos fármacos , Taninos Hidrolisáveis/farmacologia , Extratos Vegetais/química , Replicação Viral/efeitos dos fármacos , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Herpesvirus Humano 3/fisiologia , Humanos , Taninos Hidrolisáveis/isolamento & purificação , Proteínas Imediatamente Precoces/análise , Proteínas Quinases JNK Ativadas por Mitógeno/análise , Espectrometria de Massas por Ionização por Electrospray , Transativadores/análise , Proteínas do Envelope Viral/análise
5.
Phytomedicine ; 23(8): 872-81, 2016 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-27288923

RESUMO

BACKGROUND: Lindera neesiana Kurz (Lauraceae), popularly known as Siltimur in Nepal, is an aromatic and spicy plant with edible fruits. It is a traditional herbal medicine widely used for the treatment of diarrhea, tooth pain, headache, and gastric disorders and is also used as a stimulant. PURPOSE: The aim of the present study was to examine in vitro cytoprotective, anti-neuroinflammatory and neuroprotective potential of an aqueous extract of L. neesiana (LNE) fruit using different central nervous system (CNS) cell lines. METHODS: In order to study the neuroprotective potential of LNE, we used three different types of CNS cell lines: murine microglia (BV2), rat glioma (C6), and mouse neuroblastoma (N2a). Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent, and prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and nerve growth factor (NGF) release in the culture media was determined using enzyme linked immunosorbent assay (ELISA) kits. Western blot analysis was performed to determine the protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2), mitogen activated protein kinase (MAPK) family proteins, Bax, B cell lymphoma (BCL)-2, and cleaved caspase 3. Neurite outgrowth was determined using the IncuCyte imaging system. RESULTS: LNE treatment not only reduced nitric oxide (NO) production in a dose-dependent manner, but also significantly reduced proinflammatory cytokines, iNOS and COX-2 production by lipopolysaccharide (LPS) stimulated BV-2 cells. LNE increased the expression of phosphorylated (p)-extracellular signal-regulated kinase (ERK), whereas p-p38 and p- janus kinase (JNK) expression was significantly decreased in activated microglia. Furthermore, LNE increased cell viability of N2a cells, which was accompanied by decreased caspase-3 expression and the ratio of Bax/Bcl2 protein expression as well as increased NGF and neurite outgrowth, suggesting its neuroprotective potential against LPS-induced effects. Additionally, LNE substantially increased nuclear factor erythroid 2-related factor 2 (Nrf2) secretion in N2a cells and inhibited lipid dehydrogenase (LDH) release in H2O2-stimulated BV2 cells demonstrating the strong anti-inflammatory and antioxidant effects of LNE in CNS cell lines. CONCLUSION: Here we found that water the soluble extract of LNE has promising anti-neuroinflammation and anti-apoptotic properties and identify LNE as a potential natural candidate for neuroprotection.


Assuntos
Anti-Inflamatórios/farmacologia , Frutas/química , Lindera/química , Fármacos Neuroprotetores/farmacologia , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Citocinas/antagonistas & inibidores , Relação Dose-Resposta a Droga , Humanos , Camundongos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Extratos Vegetais/química , Extratos Vegetais/farmacologia
6.
Food Funct ; 6(5): 1568-77, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25832198

RESUMO

Methylglyoxal (MGO) is a highly reactive metabolite of glucose, which is known to cause damage and induce apoptosis in endothelial cells. Endothelial cell damage is implicated in the progression of diabetes-associated complications and atherosclerosis. Nuts are high in vitamin E. Consumption of nuts has been recommended for the prevention of cardiovascular disease. However, different nuts contain different forms of vitamin E, which can have different effects on endothelial cells. In this work, we investigated the protective effect of different isoforms of vitamin E on MGO-induced apoptosis in human umbilical vein endothelial cells (HUVECs). Among all forms of vitamin E, δ-tocopherol showed the highest effect on apoptosis of HUVECs. We also compared the anti-apoptotic activity of δ-tocopherol with that of α-tocopherol in MGO-treated HUVECs. Pretreatment with α- or δ-tocopherol significantly inhibited MGO-induced changes in cell morphology, cell death, and production of intracellular reactive oxygen species. δ-Tocopherol prevented MGO-induced apoptosis in HUVECs by increasing Bcl-2 expression and decreasing Bax expression. Interestingly, α-tocopherol also inhibited these factors but to a lesser extent than δ-tocopherol. MGO was found to activate mitogen-activated protein kinases (MAPKs). Compared to pretreatment with α-tocopherol, pretreatment with δ-tocopherol more strongly inhibited the activation of MAPKs, such as JNK and ERK1/2. These findings suggest that δ-tocopherol may be a more effective regulator of MGO-induced apoptosis than α-tocopherol.


Assuntos
Apoptose/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/citologia , Aldeído Pirúvico/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Tocoferóis/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos
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