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Our previous study examined the phytochemical composition and bio-activities of raw daylily flower (Hemerocallis fulva L.). However, this plant food is usually served via heat process such as cooking in a soup. This study aimed to investigate the phytochemical profile and biofunctions of steamed daylily flower (SDF). The content of total phenolic acids, total flavonoids, total carotenoids, total anthocyanins and total triterpenoids in SDF aqueous extract was assessed. Normal cardiac and hepatic cells, H9c2 and L-02 cells, were used to evaluate the protective effects of SDF against ethanol. SDF concentrations of 0.25%, 0.5%, and 1% were applied to treat H9c2 or L-02 cells for 48 h at 37 °C initially, followed by exposure to ethanol at 150 mM for 24 h at 37 °C. Results showed that the content of assessed phytochemicals was in the range of 1019-2045 mg/100 g dry weight. Flavonoids and triterpenoids were two major detected phytochemicals in SDF. SDF treatments at 0.5% and 1% increased the viability of H9c2 cells, but at three concentrations enhanced the survival of L-02 cells. SDF at 0.5% and 1% up-regulated Bcl-2 messenger RNA (mRNA) expression and down-regulated Bax mRNA expression. Ethanol increased reactive oxygen species production, decreased glutathione content, as well as lowered glutathione peroxidase and catalase activities. SDF treatments reversed these changes. SDF at 0.5% and 1% reduced the activity of cytochrome P450 2E1 and nicotinamide adenine dinucleotide phosphate oxidase, limited p47phox mRNA expression, as well as enhanced factor E2-related factor 2 and heme oxygenase-1 mRNA expression. SDF at three concentrations decreased gp91phox mRNA expression. In conclusion, these novel findings indicated that SDF aqueous extract was rich in phytochemicals and provided anti-apoptotic and anti-oxidative actions to protect cardiac and hepatic cells against ethanol. Thus, SDF might be considered as a functional food with multiple bio-activities.
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Hemerocallis , Triterpenos , Hemerocallis/química , Etanol/análise , Etanol/farmacologia , Antocianinas/análise , Antocianinas/farmacologia , Estresse Oxidativo , Flores/química , Flavonoides/farmacologia , Hepatócitos , RNA Mensageiro , Compostos Fitoquímicos/farmacologia , Triterpenos/farmacologiaRESUMO
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OBJECTIVES: Protective effects of s-methyl cysteine (SMC) alone, protocatechuic acid (PCA) alone, and SMC plus PCA against chronic ethanol consumption induced hepatic steatosis and inflammation were investigated. MATERIALS AND METHODS: Mice were divided into six groups: normal diet (ND) group, Lieber-DeCarli liquid diet without ethanol (LD diet) group, LD diet with ethanol (LED diet) group, SMC group (LED diet plus 0.25% SMC), PCA group (LED diet plus 0.25% PCA), and SMC+PCA group (LED diet plus 0.125% SMC + 0.125% PCA). After 8 weeks of supplementation, blood and liver were used for analysis. RESULTS: Biochemical and histological data showed that SMC plus PCA led to a greater reduction in lipid droplets in the liver than SMC or PCA treatment alone. SMC plus PCA resulted in greater suppression in hepatic mRNA expression of peroxisome proliferator-activated receptor-gamma, sterol regulatory element-binding protein 1c, stearoyl-CoA desaturase-1, cyclooxygenase-2, and myeloperoxidase than SMC or PCA treatment alone. SMC plus PCA led to a greater decrease in hepatic reactive oxygen species and inflammatory cytokine levels than SMC or PCA treatment alone. CONCLUSION: These novel findings suggest that the combination of SMC and PCA was a potent remedy for alcoholic liver disorders.
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BACKGROUND/AIM: The tissue inhibitor of metalloproteinase-2 (TIMP-2) is a critical inhibitor of matrix metalloproteinases (MMPs). Along with MMPs, TIMP-2 regulates the breakdown and remodeling of the extracellular matrix (ECM) and basement membranes. This study investigated the role of genotypes of the TIMP-2 -418G/C (rs8179090) single nucleotide polymorphism on lung risk. MATERIALS AND METHODS: A total of 358 lung cancer patients and 716 healthy subjects were recruited in this study. Genotypes were identified via the polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The distribution of alleles and genotype frequencies of TIMP-2 -418G/C genotypes between the two groups were compared and no statistically significant difference (p>0.05) was found. The heterozygous and homozygous variant genotypes showed no differential distribution between the control and case groups (p>0.05). CONCLUSION: TIMP-2 -418G/C variants might not be associated with lung cancer susceptibility and could not serve as predictors.
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Biomarcadores Tumorais/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Inibidor Tecidual de Metaloproteinase-2/genética , Idoso , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Fenótipo , Medição de Risco , Fatores de Risco , TaiwanRESUMO
HLE-B3 cell line, a human lens epithelial cell line, was used to examine the anti-glycative and anti-oxidative protection of aqueous extract prepared from steamed red amaranth leaves against high glucose induced injury. Phytochemical profile of this aqueous extract was analyzed. HLE-B3 cells were pretreated by this aqueous extract at 0.25%, 0.5%, or 1%, and followed by high glucose treatment. Results showed that the content of phenolic acids, flavonoids, anthocyanins, carotenoids, and triterpenoids in this aqueous extract was in the range of 1,107-2,861 mg/100 g dry weight. High glucose decreased cells viability and suppressed Bcl-2 mRNA expression. This aqueous extract pretreatments raised 11-42% cell survival and upregulated 20-47% Bcl-2 mRNA expression. High glucose reduced Na+ -K+ ATPase activity and mitochondrial membrane potential (MMP). This aqueous extract raised 27-40% Na+ -K+ ATPase activity, and 18-51% MMP. High glucose stimulated the generation of total advanced glycative endproducts (AGEs), methylglyoxal, and reactive oxygen species (ROS). This aqueous extract pretreatments lowered total AGEs, methylglyoxal, and ROS levels in the range of 0.38-1.17 folds, 1.7-4.9 nmol/mg protein, and 0.35-1.06 relative fluorescence unit/mg protein. High glucose upregulated mRNA expression of aldose reductase, nuclear factor kappa B, and p38. This aqueous extract pretreatments decreased mRNA expression of these factors in the range of 75-159%, 57-151%, and 54-166%. High glucose downregulated mRNA expression of nuclear factor E2-related factor 2 (Nrf2). This aqueous extract pretreatments increased 12-38% Nrf2 mRNA expression. These results suggested that this aqueous extract might be a potent nutritional supplement to prevent diabetic retinopathy.
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Amaranthus , Antocianinas , Glucose , Humanos , Estresse Oxidativo , Folhas de Planta , Espécies Reativas de OxigênioRESUMO
Dracorhodin can be isolated from the exudates of the fruit of Daemonorops draco. Previous studies suggested that dracorhodin perchlorate can promote fibroblast proliferation and enhance angiogenesis during wound healing. In the present study, the potential bioactivity of dracorhodin perchlorate in human HaCaT keratinocytes, were investigated in vitro, with specific focus on HaCaT wound healing. The results of in vitro scratch assay demonstrated the progressive closure of the wound after treatment with dracorhodin perchlorate in a time-dependent manner. An MTT assay and propidium iodide exclusion detected using flow cytometry were used to detect cell viability of HaCaT cells. Potential signaling pathways underlying the effects mediated by dracorhodin perchlorate in HaCaT cells were clarified by western blot analysis and kinase activity assays. Dracorhodin perchlorate significantly increased the protein expression levels of ß-catenin and activation of AKT, ERK and p38 in HaCaT cells. In addition, dracorhodin perchlorate did not induce HaCaT cell proliferation but promoted cell migration. Other mechanisms may yet be involved in the dracorhodin perchlorate-induced wound healing process of human keratinocytes. In summary, dracorhodin perchlorate may serve to be a potential molecularly-targeted phytochemical that can improve skin wound healing.
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BACKGROUND/AIM: Oridonin (Ori) is a diterpenoid naturally present in medicinal plants with a potential as an antioxidant agent. This study aimed to evaluate the hepatic anti-oxidative, anti-glycative and anti-inflammatory properties of Ori at 0.125 and 0.25% against chronic ethanol intake in mice. MATERIALS AND METHODS: Mice were divided into five groups: i) normal diet group, ii) Ori group, iii) ethanol diet (Lieber-DeCarli liquid diet with ethanol) group, iv) ethanol diet plus 0.125% Ori and v) ethanol diet plus 0.25% Ori. After 8 weeks of Ori supplementation, blood and liver tissue were used for analyses. RESULTS: Ethanol increased the production of reactive oxygen species and nitric oxide, decreased glutathione content, and lowered the activity of glutathione peroxide, glutathione reductase and catalase. Ethanol suppressed the hepatic mRNA expression of nuclear factor E2-related factor 2. Ori supplements reversed these changes. Ethanol increased hepatic Ne-(carboxyethymethyl)-lysine (CML) and pentosidine levels, and enhanced aldose reductase (AR) activity and mRNA expression. Ori supplements at only 0.25% decreased CML and pentosidine levels, and lowered the AR activity as well as its mRNA expression. Ethanol increased the hepatic release of tumor necrosis factor-alpha, transforming growth factor-beta1, interleukin (IL)-1beta and IL-6. Histological data showed that ethanol induced necrosis and inflammatory cell infiltration, while Ori supplements alleviated these inflammatory responses. Ethanol up-regulated the hepatic mRNA expression of nuclear factor kappa B, myeloperoxidase and p38. Ori supplements reversed these changes. CONCLUSIONS: These novel findings suggest that Ori could be used as a potent agent against alcohol-induced hepatotoxicity.
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Alcoolismo , Consumo de Bebidas Alcoólicas , Animais , Diterpenos do Tipo Caurano , Fígado/metabolismo , Camundongos , Estresse OxidativoRESUMO
Renal protection from s-ethyl cysteine (SEC) against cisplatin (CP)-induced inflammatory and oxidative injury was examined. Mice were divided into five groups: normal group, 0.25% SEC group, CP group, 0.125% SEC + CP group, 0.25% SEC + CP group. After 2 weeks supplementation, mice of CP and SEC + CP groups received CP treatment. H&E stain showed that CP caused infiltration of inflammatory cells and necrosis of tubular cells. SEC pre-treatments attenuated CP-induced inflammatory injury and degeneration. SEC pre-treatments limited CP-stimulated release of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha and prostaglandin E2 in kidney. CP raised the renal activity and mRNA expression of cyclooxygenase-2 and nuclear factor kappa B. SEC pre-treatments reversed these alterations. CP increased the production of reactive oxygen species and nitric oxide, and lowered glutathione content, glutathione peroxidase and glutathione reductase activities in kidney. SEC pre-treatments reversed these changes. CP up-regulated renal inducible nitric oxide synthase (iNOS) mRNA expression, and down-regulated nuclear factor E2-related factor (Nrf)-2 and heme oxygenase (HO)-1 mRNA expression. SEC pre-treatments suppressed iNOS mRNA expression; and enhanced renal Nrf2 and HO-1 mRNA expression. These novel findings suggest that dietary SEC via exerting its multiple bio-functions could be considered as a protective agent for kidney against CP.
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Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Cisteína/análogos & derivados , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Nitrogênio da Ureia Sanguínea , Creatina/sangue , Creatina/urina , Cisteína/uso terapêutico , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Heme Oxigenase-1/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND/AIM: The studies about the roles of matrix metalloproteinases (MMPs) in pterygium diagnosis and/or prognosis are mainly based on their mRNA and protein levels, while the genomic roles of MMPs are seldom examined. The aim of this study was to investigate the contribution of MMP-9 genotypes to pterygium risk. MATERIALS AND METHODS: MMP-9 rs3918242 was genotyped in 134 pterygium cases and 268 controls via polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The rs3918242 genotype percentages of CC, CT, and TT were 73.1, 25.4 and 1.5% among cases and 74.6, 23.1 and 2.3% among controls (p trend=0.7928). The odds ratios after adjusting for age and gender for CT and TT genotypes at rs3918242 were 1.08 and 0.92 (95%CI=0.66-1.73 and 0.45-2.89, p=0.6478 and 0.6389), respectively. In addition, allelic frequency analysis showed no significant difference in the distribution of allelic frequencies between the pterygium and control groups. CONCLUSION: The genotypes at MMP-9 rs3918242 play a minor role in determining personal susceptibility to pterygium.
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Povo Asiático/genética , Metaloproteinase 9 da Matriz/genética , Polimorfismo de Nucleotídeo Único , Pterígio/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas , Pterígio/diagnóstico , TaiwanRESUMO
Allyl isothiocyanate (AITC), a bioactive phytochemical compound that is a constituent of dietary cruciferous vegetables, possesses promising chemopreventive and anticancer effects. However, reports of AITC exerting antitumor effects on apoptosis induction of colorectal cancer (CRC) cells in vitro are not well elucidated. The present study focused on the functional mechanism of the endoplasmic reticulum (ER) stressbased apoptotic machinery induced by AITC in human colorectal cancer HT29 cells. Our results indicated that AITC decreased cell growth and number, reduced viability, and facilitated morphological changes of apoptotic cell death. DNA analysis by flow cytometry showed G2/M phase arrest, and alterations in the modulated protein levels caused by AITC were detected via western blot analysis. AITC also triggered vital intrinsic apoptotic factors (caspase9/caspase3 activity), disrupted mitochondrial membrane potential, and stimulated mitochondrialrelated apoptotic molecules (e.g., cytochrome c, apoptotic protease activating factor 1, apoptosisinducing factor, and endonuclease G). Additionally, AITC prompted induced cytosolic Ca2+ release and Ca2+dependent ER stressrelated signals, such as calpain 1, activating transcription factor 6α, glucoseregulated proteins 78 and 94, growth arrest and DNA damageinducible protein 153 (GADD153), and caspase4. The level of reactive oxygen species (ROS) production was found to induce the hallmark of ER stress GADD153, proapoptotic marker caspase3, and calpain activity after AITC treatment. Our findings showed for the first time that AITC induced G2/M phase arrest and apoptotic death via ROSbased ER stress and the intrinsic pathway (mitochondrialdependent) in HT29 cells. Overall, AITC may exert an epigenetic effect and is a potential bioactive compound for CRC treatment.
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Adenocarcinoma/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Isotiocianatos/farmacologia , Mitocôndrias/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Células Tumorais CultivadasRESUMO
BACKGROUND/AIM: Few studies have examined the contribution of matrix metalloproteinases (MMP) to either diagnosis or prognosis of pterygium. The aim of this study was to investigate the contribution of MMP-1 genotypes to pterygium risk. PATIENTS AND METHODS: A total of 134 cases and 268 controls were included and their MMP-1 -1607 (rs1799705) genotypes were examined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The percentages of 2G/2G, 1G/2G, and 1G/1G for rs1799705 genotypes were 48.5, 36.6 and 14.9% among patients and 33.9, 44.8, and 21.3% among controls (p trend=0.0167). The odds ratios (ORs) after adjusting for age and gender for 1G/2G and 1G/1G genotypes at rs1799705 were 0.54 (95%CI=0.33-0.89, p=0.0168) and 0.46 (95%CI=0.27-0.88, p=0.0192), respectively. Consistently, the adjusted OR for those carrying the 1G allele at MMP-1 -1607 was 0.61 (95%CI=0.41-0.78, p=0.0167), compared with the wild-type 2G allele. CONCLUSION: The genotypes at rs1799705 play a role in determining personal susceptibility to pterygium.
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Metaloproteinase 1 da Matriz/genética , Pterígio/genética , Idoso , Idoso de 80 Anos ou mais , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Pterígio/enzimologia , Pterígio/epidemiologia , Taiwan/epidemiologiaRESUMO
The effects of two-drug combination, all-trans retinoic acid (ATRA) and bisdemethoxycurcumin (BDMC), on apoptosis induction of liver cancer cells were investigated in human liver Hep 3B cells. Two-drug combination caused a more effective decrease in cell viability and in induction of S phase arrest, DNA damage, and cell apoptosis than that of ATRA or BDMC only. Also, the two-drug combination caused more cells to undergo significantly increased ROS productions when compared to that of ATRA or BDMC only. Results of Western blotting demonstrated that two-drug combination increased expressions of Fas, pro-apoptotic proteins, and active form of caspase-3 and -9, but decreased that of anti-apoptotic proteins and XIAP than that of ATRA or BDMC only in Hep 3B cells. In conclusion, ATRA combined with BDMC enhance cell apoptosis and associated protein expression in Hep 3B cells. PRACTICAL APPLICATIONS: Bisdemethoxycurcumin (BDMC) derived from natural plants, turmeric (Curcuma longa), which had been used for Asia food for thousands of years. All-trans retinoid acid (ATRA) is currently used as a primary treatment for patients with acute promyelocytic leukemia. In previous study, ATRA and BDMC were reported to have anti-inflammatory and anticancer effects. Our results showed that treatment of ATRA combined with BDMC showed more effectively apoptosis than that of ATRA or BDMC only in Hep 3B cells. The findings also provided possible pathways concerning the induction of liver cancer cell apoptosis. We conclude that ATRA combined with BDMC may be potent anticancer agents or adjuvants for liver cancer therapy in the future.
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Curcumina , Neoplasias Hepáticas , Apoptose , Linhagem Celular Tumoral , Curcumina/farmacologia , Diarileptanoides , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Tretinoína/farmacologiaRESUMO
Ligustrum lucidum Ait (LL), Lysimachia christinae Hance (LC), Mentha piperita Linn (MP), and Cinnamomum cassia Presl (CC) are common spices used in Asia. The present study investigated the anti-Salmonella effects of the four spices using aqueous extracts. The amount of phenolic acids and flavonoids in each spice aqueous extract was determined as indicators of purity. Mice were pretreated with LL, LC, MP or CC aqueous extract for 7 days. Following infection with Salmonella enterica serovar Typhimurium strain ST21 (ST21), the aqueous extract of each spice was subsequently administered for 4 days. ST21 infected mice had lower body weight compared with the control group. The administration of spice aqueous extracts significantly increased body weight following infection. ST21 infection increased the fecal ST21 counts compared with the control group; however, following spice aqueous extract treatments, ST21 counts significantly decreased. The spice treatments also significantly reduced ST21 count in blood and the organs. Notably, ST21 infection increased interferon (IFN)-γ and interleukin (IL)-6 levels in serum whilst spice treatments reduced these cytokines. In the spleen, spice treatment significantly lowered IFN-γ, IL-6, IL-1ß, and tumor necrosis factor (TNF)-α levels, but increased IL-12 levels. ST21 infection stimulated the production of immunoglobulin (Ig)A and IgM in serum whilst spice aqueous extract treatment significantly decreased these levels. In summary, LL and MP aqueous extract treatments had the most significant effect in protecting against ST21 infection. Results of the RAW 264.7 cell infection model suggested that the mechanisms involved in the anti-ST21 effect of each spice were individually different. All four aqueous extracts demonstrated different mechanisms in attenuating ST21 invasion with the protective effect of LC aqueous extract potentially involving TNF-α expression. The present findings suggested that the four spices may be considered as potent functional foods due to their anti-Salmonella effects.
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Objective: The effects of pre-treatments from s-methyl cysteine (SMC) alone, syringic acid (SA) alone and SMC plus SA against kainic acid (KA) induced injury in nerve growth factor (NGF) differentiated PC12 cells were investigated. Methods: NGF-differentiated PC12 cells were treated with 1 µM SMC, 1 µM SA or 0.5 µM SMC plus 0.5 µM SA for 2 days. Subsequently, cells were further treated by 150 µM KA. Results: KA suppressed Bcl-2 mRNA expression, enhanced Bax mRNA expression and casued cell death. SMC was greater than SA, and similar as SMC+SA in increasing Bcl-2 mRNA expression. SMC+SA led to greater increase in mitochondrial membrane potential and cell survival than SMC or SA alone. SMC+SA resulted in more reduction in reactive oxygen species and tumor necrosis factor-alpha generation, more increase in glutathione content and glutathione reductase activity than SMC or SA alone. KA up-regulated protein expression of nuclear factor kappa B (NF-κB) p65 and phosphorylated p38 (p-p38). SMC or SA pre-treatments alone limited protein expression of both factors. SMC+SA resulted in more suppression in NF-κB p65 and p-p38 expression. KA decreased glutamine level, increased glutamate level and stimulated calcium release. SMC pre-treatments alone reversed these alterations. SMC alone elevated glutamine synthetase (GS) activity and mRNA expression. SMC+SA led to greater GS activity and mRNA expression than SMC pre-treatments alone. Conclusion: These findings suggested that this combination, SMC+SA, might provide greater protective potent for neuronal cells.
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Cisteína/análogos & derivados , Ácido Gálico/análogos & derivados , Fator de Crescimento Neural/farmacologia , Fármacos Neuroprotetores/farmacologia , Animais , Cálcio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/patologia , Sobrevivência Celular , Cisteína/farmacologia , Sinergismo Farmacológico , Ácido Gálico/farmacologia , Ácido Caínico/toxicidade , Potencial da Membrana Mitocondrial/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Ratos , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Oridonin (ORI) is a natural diterpenoid presented in some medicinal plants. The effects of pre-treatments from ORI against MPP+- or kainic acid (KA)-induced damage in nerve growth factor (NGF)-differentiated PC12â¯cells were investigated. Results showed that pre-treatments of ORI at 0.25-2⯵M enhanced the viability and plasma membrane integrity of NGF-differentiated PC12â¯cells. MPP+ or KA exposure down-regulated Bcl-2 mRNA expression, up-regulated Bax mRNA expression, increased caspase-3 activity and decreased Na+-K+ ATPase activity. ORI pre-treatments at test concentrations reversed these changes. ORI pre-treatments decreased reactive oxygen species production, raised glutathione level, and increased glutathione peroxidase, glutathione reductase and catalase activities in MPP+ or KA treated cells. ORI pre-treatments lowered tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6 and prostaglandin E2 levels in MPP+ or KA treated cells. ORI also diminished MPP+ or KA induced increase in nuclear factor-κB binding activity. MPP+ exposure suppressed tyrosine hydroxylase (TH) mRNA expression and decreased dopamine content. KA exposure reduced glutamine synthetase (GS) mRNA expression, raised glutamate level and lowered glutamine level. ORI pre-treatments at 0.5-2⯵M up-regulated mRNA expression of TH and GS, restored DA and glutamine content. These findings suggested that oridonin was a potent neuro-protective agent against Parkinson's disease and seizure.
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1-Metil-4-fenilpiridínio/efeitos adversos , Diterpenos do Tipo Caurano/farmacologia , Ácido Caínico/efeitos adversos , Fármacos Neuroprotetores/farmacologia , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Membrana Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Diterpenos do Tipo Caurano/toxicidade , Regulação para Baixo/efeitos dos fármacos , Glutamato-Amônia Ligase/genética , Glutamato-Amônia Ligase/metabolismo , Fármacos Neuroprotetores/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , RNA Mensageiro/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Cantharidin (CTD), a sesquiterpenoid bioactive substance, has been reported to exhibit anticancer activity against various types of cancer cells. The aim of the present study was to investigate the apoptosis effects and the underlying mechanisms of CTD on osteosarcoma U-2 OS cells. Results showed that CTD induced cell morphologic changes, reduced total viable cells, induced DNA damage, and G2/M phase arrest. CTD increased the production of reactive oxygen species and Ca2+, and elevated the activities of caspase-3 and -9, but decreased the level of mitochondrial membrane potential. Furthermore, CTD increased the ROS- and ER stress-associated protein expressions and increased the levels of pro-apoptosis-associated proteins, but decreased that of anti-apoptosis-associated proteins. Based on these observations, we suggested that CTD decreased cell number through G2/M phase arrest and the induction of cell apoptosis in U-2 OS cells and CTD could be a potential candidate for osteosarcoma treatments.
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Apoptose/efeitos dos fármacos , Cantaridina/farmacologia , Divisão Celular/efeitos dos fármacos , Fase G2/efeitos dos fármacos , Osteossarcoma/patologia , Cálcio/metabolismo , Caspases/metabolismo , Linhagem Celular Tumoral , Cromatina/efeitos dos fármacos , Cromatina/metabolismo , Dano ao DNA , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Osteossarcoma/enzimologia , Osteossarcoma/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
The effects of Gynura bicolor aqueous extract (GAE) upon glycemic control, coagulation disorder, lipid accumulation, and glycative, oxidative, and inflammatory stresses in diabetic mice were investigated. Mice were treated with streptozotocin to induce type 1 diabetes. Diabetic mice were divided into four groups, consumed GAE at 0%, 0.25%, 0.5%, or 1%. Normal group consumed standard mouse basal diet. After 8-week treatments, mice were sacrificed after overnight fasting. Results showed that GAE supplement at 0.5% and 1% decreased plasma glucose level and increased plasma insulin level. Diabetes lowered plasma level of protein C and anti-thrombin III; and raised plasminogen activator inhibitor-1 activity and fibrinogen level in plasma. GAE supplement at 0.5% and 1% reversed these alterations. Histological data, assayed by Oil Red O stain, indicated that GAE supplement decreased lipid accumulation in liver. GAE supplement at 0.5% and 1% reduced aldose reductase activity in heart and kidney; and lowered the levels of carboxymethyllysine and pentosidine in plasma and two organs. Diabetes decreased glutathione content, and increased reactive oxygen species, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α production in heart and kidney. GAE supplement at three test doses reversed these changes. Diabetes upregulated the mRNA expression of p38 and nuclear factor kappa (NF-κ)B in heart and kidney. GAE supplement suppressed the mRNA expression of both p38 and NF-κB. These novel findings suggest that Gynura bicolor is a potent functional food for diabetic prevention or alleviation.
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Antidiuréticos/administração & dosagem , Asteraceae/química , Diabetes Mellitus Experimental/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Arginina/análogos & derivados , Arginina/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Glutationa/metabolismo , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Lisina/análogos & derivados , Lisina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
The purpose of present HUVE cells and mice study was to investigate the combined effects of carnosine and asiatic acid (AA) against diabetic progression. In HUVE cells, high glucose decreased cell viability, reduced Bcl-2 mRNA expression and increased Bax mRNA expression. The co-treatment of 0.5⯵M carnosine plus 0.5⯵M AA led to greater cell viability and Bcl-2 mRNA expression than 1⯵M carnosine or 1⯵M AA treatment alone. This combination more significantly decreased the production of DNA fragmentation, tumor necrosis factor (TNF)-alpha, reactive oxygen species (ROS), and nuclear factor kappa B binding activity than carnosine or AA treatment alone. In diabetic mice, the combination of 0.25% carnosine plus 0.25% AA in diet resulted in higher final body weight, and lower levels of plasma glucose and triglyceride than 0.5% carnosine or 0.5% AA treatment alone. Carnosine and AA combination caused more reduction in renal levels of leukin-6, TNF-alpha and ROS than carnosine or AA treatment alone. This combination also more significantly limited renal cyclooxygenase-2 activity and p-p38 phosphorylation than carnosine or AA treatment alone. These novel findings support that this combination is a more powerful remedy for diabetic control.
Assuntos
Anti-Inflamatórios/administração & dosagem , Carnosina/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Triterpenos Pentacíclicos/administração & dosagem , Animais , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/imunologia , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/imunologia , Sinergismo Farmacológico , Células Endoteliais da Veia Umbilical Humana/imunologia , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/genética , NF-kappa B/imunologia , Espécies Reativas de Oxigênio/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
The content of nitric oxide (NO), 3-nitrotyrosine, advanced glycation endproducts (AGEs) and trans fatty acids (TFAs) in 16 kinds of cured meat products was examined. Results showed that NO and 3-nitrotyrosine levels were in the range of non-detectable to 4.6 µM/mg protein, and non-detectable to 0.49 nmol/mg protein, respectively. Carboxymethyllysine could be detected in 13 kinds of cured meat products; its content was in the range of 48-306 µg/100 g meat. Pentosidine was found in 14 kinds of meat products, in the range of 109-631 µg/100 g meat. Furosine was presented in all test meat samples, in the range of 156-676 µg/100 g meat. Palmitelaidic acid was found in 3 kinds of meat product, and the content was in the range of 0.59-0.71%. Vaccenic acid was presented in 9 kinds of meat products; its content was in the range of 0.89-1.47%. Elaidic acid was detected in 5 kinds of meat products, and the content was in the range of 0.67-1.21%. Because NO, 3-nitrotyrosine and AGEs might have adverse impact upon health, people with certain healthy conditions should carefully consider the frequency and amount of consumption for these cured meat products.