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1.
Braz. j. med. biol. res ; 53(6): e9489, 2020. graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1132521

ABSTRACT

Rheumatoid arthritis (RA) is an autoimmune disease of knee joints involving pain and inflammation. Rhoifolin is a plant flavonoid known to have antioxidant and anti-inflammatory properties. This study was taken to identify the effect of rhoifolin on complete Freund's adjuvant (CFA)-induced arthritis in the rat model. Treatment with rhoifolin (10 and 20 mg/kg) showed a significant improvement in the overall health parameters such as paw edema and weight loss. This improvement in morphological parameters corroborated the findings with gross morphological changes observed in the histopathological analysis. Rhoifolin treatment also caused a significant decrease in oxidative stress, evident from changes in intracellular levels of glutathione, glutathione peroxidase, malondialdehyde, and superoxide dismutase in the articular cartilage tissue. Moreover, proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin(IL)-1β, and IL-6 showed a significant downregulation of gene expression and intracellular protein concentration levels. The NF-κB pathway showed a significant attenuation as evident in the significant reduction in the levels of NF-κB p65 and p-IκB-α. These results indicated that rhoifolin can be a natural therapeutic alternative to the extant regimens, which include non-steroidal anti-inflammatory drugs and immunosuppressants. Additionally, the antioxidant and anti-inflammatory action of rhoifolin was probably mediated by the NF-κB pathway. However, the exact target molecules of this pathway need to be determined in further studies.


Subject(s)
Animals , Male , Rats , Arthritis, Experimental/drug therapy , Arthritis, Rheumatoid/drug therapy , Flavonoids/administration & dosage , Freund's Adjuvant/administration & dosage , Cytokines/blood , Oxidative Stress/drug effects , Disaccharides/administration & dosage , Arthritis, Experimental/metabolism , Arthritis, Rheumatoid/metabolism , Biomarkers/blood , NF-kappa B/drug effects , NF-kappa B/metabolism , Interleukin-6/blood , Tumor Necrosis Factor-alpha/blood , Interleukin-1beta/blood , Glycosides/administration & dosage
2.
Acta cir. bras ; 34(11): e201901104, Nov. 2019. graf
Article in English | LILACS | ID: biblio-1054677

ABSTRACT

Abstract Purpose: Myocardial ischemia/reperfusion (Ml/R) injury is a leading cause of damage in cardiac tissues, with high rates of mortality and disability. Biochanin A (BCA) is a main constituent of Trifolium pratense L. This study was intended to explore the effect of BCA on Ml/R injury and explore the potential mechanism. Methods: In vivo MI/R injury was established by transient coronary ligation in Sprague-Dawley rats. Triphenyltetrazolium chloride staining (TTC) was used to measure myocardial infarct size. ELISA assay was employed to evaluate the levels of myocardial enzyme and inflammatory cytokines. Western blot assay was conducted to detect related protein levels in myocardial tissues. Results: BCA significantly ameliorated myocardial infarction area, reduced the release of myocardial enzyme levels including aspartate transaminase (AST), creatine kinase (CK-MB) and lactic dehydrogenase (LDH). It also decreased the production of inflammatory cytokines (IL-1β, IL-18, IL-6 and TNF-α) in serum of Ml/R rats. Further mechanism studies demonstrated that BCA inhibited inflammatory reaction through blocking TLR4/NF-kB/NLRP3 signaling pathway. Conclusion: The present study is the first evidence demonstrating that BCA attenuated Ml/R injury through suppressing TLR4/NF-kB/NLRP3 signaling pathway-mediated anti-inflammation pathway.


Subject(s)
Animals , Male , Cardiotonic Agents/pharmacology , Myocardial Reperfusion Injury/prevention & control , NF-kappa B/drug effects , Genistein/pharmacology , Toll-Like Receptor 4/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/drug effects , Aspartate Aminotransferases/blood , Reference Values , Myocardial Reperfusion Injury/metabolism , Signal Transduction/drug effects , Blotting, Western , Reproducibility of Results , Cytokines/blood , NF-kappa B/metabolism , Rats, Sprague-Dawley , Creatine Kinase/blood , Lactate Dehydrogenases/blood , Toll-Like Receptor 4/metabolism , Anti-Inflammatory Agents/pharmacology
3.
Braz. j. med. biol. res ; 52(7): e8092, 2019. tab, graf
Article in English | LILACS | ID: biblio-1011595

ABSTRACT

Acute lung injury (ALI) is a serious clinical syndrome with a high rate of mortality. The activation of inflammation is well-recognized as a vital factor in the pathogenesis of lipopolysaccharide (LPS)-induced ALI. Therefore, suppression of the inflammatory response could be an ideal strategy to prevent ALI. Epigallocatechin-3-gallate (EGCG), mainly from green tea, has been shown to have an anti-inflammatory effect. The aim of the study was to explore whether EGCG alleviates inflammation in sepsis-related ALI. Male BALB/C mice were treated with EGCG (10 mg/kg) intraperitoneally (ip) 1 h before LPS injection (10 mg/kg, ip). The results showed that EGCG attenuated LPS-induced ALI as it decreased the changes in blood gases and reduced the histological lesions, wet-to-dry weight ratios, and myeloperoxidase (MPO) activity. In addition, EGCG significantly decreased the expression of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the lung, serum, and bronchoalveolar lavage fluid, and alleviated the expression of TLR-4, MyD88, TRIF, and p-p65 in the lung tissue. In addition, it increased the expression of IκB-α and had no influence on the expression of p65. Collectively, these results demonstrated the protective effects of EGCG against LPS-induced ALI in mice through its anti-inflammatory effect that may be attributed to the suppression of the activation of TLR 4-dependent NF-κB signaling pathways.


Subject(s)
Animals , Male , Rabbits , Catechin/analogs & derivatives , NF-kappa B/drug effects , Toll-Like Receptor 4/drug effects , Acute Lung Injury/prevention & control , Signal Transduction/drug effects , Catechin/administration & dosage , Lipopolysaccharides , Disease Models, Animal , Acute Lung Injury/chemically induced , Mice, Inbred BALB C
4.
J. appl. oral sci ; 27: e20180713, 2019. tab, graf
Article in English | LILACS, BBO | ID: biblio-1040234

ABSTRACT

Abstract Vitamin D has been known to have important regulatory functions in inflammation and immune response and shows inhibitory effects on experimental periodontitis in animal models. However, the potential mechanism has yet to be clarified. Recent studies have highlighted Aryl hydrocarbon receptor (AhR) and its downstream signaling as a crucial regulator of immune homeostasis and inflammatory regulation. Objective: This study aimed to clarify the effect of 1,25-dihydroxyvitamin D3 (VD3) on experimental periodontitis and AhR/nuclear factor-κB (NF-κB)/NLR pyrin domain-containing 3 (NLRP3) inflammasome pathway in the gingival epithelium in a murine model. Methodology: We induced periodontitis in male C57BL/6 wild-type mice by oral inoculation of Porphyromonas gingivalis (P. gingivalis), and subsequently gave intraperitoneal VD3 injection to the mice every other day for 8 weeks. Afterwards, we examined the alveolar bone using scanning electron microscopy (SEM) and detected the gingival epithelial protein using western blot analysis and immunohistochemical staining. Results: SEM images demonstrated that alveolar bone loss was reduced in the periodontitis mouse model after VD3 supplementation. Western blot analyses and immunohistochemical staining of the gingival epithelium showed that the expression of vitamin D receptor, AhR and its downstream cytochrome P450 1A1 were enhanced upon VD3 application. Additionally, VD3 decreased NF-κB p65 phosphorylation, and NLRP3, apoptosis-associated speck-like protein, caspase-1, interleukin-1β (IL-1β) and IL-6 protein expression. Conclusions: These results implicate the alleviation of periodontitis and the alteration of AhR/NF-κB/NLRP3 inflammasome pathway by VD3 in the mouse model. The attenuation of this periodontal disease may correlate with the regulation of AhR/NF-κB/NLRP3 inflammasome pathway by VD3.


Subject(s)
Animals , Male , Periodontitis/metabolism , Periodontitis/drug therapy , Calcitriol/pharmacology , NF-kappa B/drug effects , Bone Density Conservation Agents/pharmacology , NLR Family, Pyrin Domain-Containing 3 Protein/drug effects , Periodontitis/pathology , Reference Values , Calcitriol/analysis , Immunohistochemistry , Blotting, Western , Reproducibility of Results , Alveolar Bone Loss , NF-kappa B/analysis , Interleukin-6/analysis , Treatment Outcome , Receptors, Aryl Hydrocarbon/analysis , Receptors, Aryl Hydrocarbon/drug effects , Porphyromonas gingivalis , Caspase 1/analysis , Bone Density Conservation Agents/analysis , Interleukin-1beta/analysis , NLR Family, Pyrin Domain-Containing 3 Protein/analysis , Gingiva/drug effects , Gingiva/metabolism , Gingiva/pathology , Mice, Inbred C57BL
5.
Acta cir. bras ; 33(7): 556-564, July 2018. tab, graf
Article in English | LILACS | ID: biblio-949368

ABSTRACT

Abstract Purpose: To investigate the effects of baicalin on inflammatory reaction, oxidative stress and protein kinase D1 (PKD1) and nuclear factor-kappa B (NF-κB) protein expressions in severe acute pancreatitis (SAP) rats. Methods: Sixty rats were divided into sham operation, model, and low-, medium- and high-dose baicalin group. SAP model was established in later 4 groups. The later 3 groups were injected with 0.1, 0.2 and 0.4 ml/100 g 5% baicalin injection, respectively. At 12 h, the serum SAP related indexes and inflammatory factors, peripheral blood CD3 and γδT cell percentages, wet/dry ratio and pancreas ascites volume, oxidative stress indexes and PKD1 and NF-κB protein expressions in pancreatic tissue were determined. Results: Compared with model group, in high-dose baicalin group the wet/dry ratio and ascites volume, serum amylase level, phospholipase A2 activity, TNF-α, IL-1 and IL-6 levels, and pancreatic malondialdehyde level and PKD1 and NF-κB protein expression were significantly decreased (P < 0.05), and peripheral blood CD3 and γδT cell percentages and pancreatic superoxide dismutase and glutathione peroxidase levels were significantly increased (P < 0.05). Conclusion: Baicalin can resist the inflammatory reaction and oxidative stress, and down-regulate protein kinase D1 and nuclear factor-kappa B protein expressions, thus exerting the protective effects on severe acute pancreatitis in rats.


Subject(s)
Animals , Pancreatitis/drug therapy , Flavonoids/pharmacology , Protein Kinase C/metabolism , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , NF-kappa B/metabolism , Oxidative Stress/drug effects , Pancreatitis/metabolism , Superoxide Dismutase/drug effects , Protein Kinase C/drug effects , Random Allocation , Down-Regulation/drug effects , Reproducibility of Results , NF-kappa B/drug effects , Interleukin-6/blood , Interleukin-1/blood , Tumor Necrosis Factor-alpha/blood , Treatment Outcome , Rats, Sprague-Dawley , CD3 Complex/drug effects , CD3 Complex/blood , Glutathione Peroxidase/drug effects , Glutathione Peroxidase/metabolism , Amylases/drug effects , Amylases/blood , Malondialdehyde/metabolism
6.
Int. j. morphol ; 36(2): 454-459, jun. 2018. graf
Article in Spanish | LILACS | ID: biblio-954136

ABSTRACT

Berberis darwinii Hook es una especie que habita el sur de Chile y la Patagonia, utilizada por la etnia mapuche para el tratamiento de procesos inflamatorios, estados febriles y dolor de estomacal. El propósito del siguiente estudio fue evaluar in vitro las propiedades del extracto total y de alcaloides de raíz de B. darwinii sobre viabilidad celular y la translocación del factor nuclear NF-kB en línea celular RAW 264.7. Se observó que los extractos no afectan negativamente la viabilidad en las células e inhibieron la translocación del factor nuclear NF-kB asociado a la modulación de la inflamación solo frente al extracto total. Estos resultados indicarían que B. darwinii podría inhibir algunos mecanismos específicos de la defensa celular al modular la translocación de NF- kB.


Berberis darwinii Hook is a species that inhabits southern Chile and Patagonia, used by the Mapuche ethnic group for the treatment of inflammatory processes, febrile states and stomach pain. The purpose of the following study was to evaluate in vitro the properties of the total extract and alkaloids of the root of B. darwinii on cell viability and the translocation of the nuclear factor NF-kB in cell line RAW 264.7. It was observed that the extracts did not negatively affect the viability in the cells and inhibited the translocation of the nuclear factor NF-kB associated with the modulation of inflammation only against the total extract. These results indicate that B. darwinii could inhibit some specific mechanisms of cell defense by modulating the translocation of NF-kB.


Subject(s)
Plant Extracts/pharmacology , NF-kappa B/drug effects , Berberis , RAW 264.7 Cells/drug effects , Cell Survival/drug effects , Fluorescent Antibody Technique , Plant Roots , Methanol , Alkaloids/pharmacology , Flow Cytometry , Immunologic Factors/pharmacology
7.
Bol. latinoam. Caribe plantas med. aromát ; 17(3): 259-269, mayo 2018. tab, ilus, graf
Article in Spanish | LILACS | ID: biblio-915349

ABSTRACT

Berberis darwinii Hook es una especie que habita el sur de Chile y la Patagonia. Siendo utilizada por la etnia mapuche para el tratamiento de procesos inflamatorios, estados febriles, y dolor estomacal. El propósito del siguiente estudio fue evaluar in vitro las propiedades del extracto de alcaloides de raíz de B. darwinii sobre respuestas celulares en monocitos desde sangre periférica de rata. Los resultados de la cuantificación del extracto muestran una concentración de alcaloides totales de 1,67 mg/g y la caracterización por HPLC- MS determinó la presencia de berberina y palmatina. In vitro se observó que los extractos disminuyeron la capacidad de adhesión y la actividad fagocítica de los monocitos e inhibieron la translocación del factor nuclear NF-κB asociado a la modulación de la inflamación, pero no así la producción de anión superóxido. Estos resultados indicarían que los alcaloides totales de B. darwinii inhiben algunos mecanismos específicos de defensa celular.


Berberis darwinii Hook is a species that inhabits southern Chile and Patagonia. This is being used by the Mapuche ethnic group for the treatment of inflammatory processes, febrile states, and stomach pain. The purpose of the following study was to evaluate in vitro the properties of an alkaloid extract of B. darwinii root on cellular responses in monocytes from the rat peripheral blood. The results of the quantification of the extract showed a total alkaloid concentration of 1.67 mg/g and the characterization by HPLC-MS determined the presence of berberine and palmatine. In vitro, it was observed that the extracts decreased the adhesion capacity and phagocytic activity of the monocytes and inhibited the translocation of the nuclear factor NF-κB associated with the modulation of inflammation, but not the production of superoxide anion. These results indicate that the total alkaloids of B. darwinii inhibit some specific mechanisms of cellular defense.


Subject(s)
Animals , Male , Rats , Plant Extracts/pharmacology , Plant Roots/chemistry , Berberis/chemistry , Plant Extracts/chemistry , Monocytes/drug effects , Cell Adhesion/drug effects , Chromatography, High Pressure Liquid/methods , NF-kappa B/drug effects , Rats, Sprague-Dawley , Alkaloids/analysis
8.
Braz. j. med. biol. res ; 51(8): e6896, 2018. graf
Article in English | LILACS | ID: biblio-951743

ABSTRACT

Excessive exposure to ultraviolet (UV) rays can cause damage of the skin and may induce cancer, immunosuppression, photoaging, and inflammation. The long non-coding RNA (lncRNA) HOX antisense intergenic RNA (HOTAIR) is involved in multiple human biological processes. However, its role in UVB-induced keratinocyte injury is unclear. This study was performed to investigate the effects of HOTAIR in UVB-induced apoptosis and inflammatory injury in human keratinocytes (HaCaT cells). Quantitative real-time polymerase chain reaction was performed to analyze the expression levels of HOTAIR, PKR, TNF-α, and IL-6. Cell viability was measured using trypan blue exclusion method and cell apoptosis using flow cytometry and western blot. ELISA was used to measure the concentrations of TNF-α and IL-6. Western blot was used to measure the expression of PKR, apoptosis-related proteins, and PI3K/AKT and NF-κB pathway proteins. UVB induced HaCaT cell injury by inhibiting cell viability and promoting cell apoptosis and expressions of IL-6 and TNF-α. UVB also promoted the expression of HOTAIR. HOTAIR suppression increased cell viability and decreased apoptosis and expression of inflammatory factors in UVB-treated cells. HOTAIR also promoted the expression of PKR. Overexpression of HOTAIR decreased cell viability and increased cell apoptosis and expression of inflammatory factors in UVB-treated cells by upregulating PKR. Overexpression of PKR decreased cell viability and promoted cell apoptosis in UVB-treated cells. Overexpression of PKR activated PI3K/AKT and NF-κB pathways. Our findings identified an essential role of HOTAIR in promoting UVB-induced apoptosis and inflammatory injury by up-regulating PKR in keratinocytes.


Subject(s)
Humans , Keratinocytes/metabolism , Apoptosis/physiology , eIF-2 Kinase/metabolism , Apoptosis Inducing Factor/metabolism , RNA, Long Noncoding/metabolism , Ultraviolet Rays/adverse effects , Gene Expression , Keratinocytes/radiation effects , Up-Regulation , Cell Survival/physiology , NF-kappa B/drug effects , NF-kappa B/metabolism , Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/metabolism , Apoptosis/radiation effects , Phosphatidylinositol 3-Kinases/metabolism , Inflammation/etiology
9.
Braz. j. med. biol. res ; 51(10): e7476, 2018. graf
Article in English | LILACS | ID: biblio-951713

ABSTRACT

Tubular-interstitial nephritis (TIN) is characterized by tubular cell damage and inflammatory lesions of kidneys. Baicalein (BAI) is a flavonoid compound found in the roots of Scutellaria baicalensis Georgi. The present study was undertaken to explore the anti-inflammatory and anti-oxidative effects of BAI on TIN patients and a lipopolysaccharide (LPS)-induced TIN cell model. The expression levels of interleukin-6 (IL-6), IL-10, and tumor necrosis factor α in serum samples of TIN patients and culture supernatants of renal proximal tubular epithelial cells (RPTECs) were evaluated using enzyme-linked immunosorbent assay. Creatinine clearance was calculated using the Cockcroft-Gault equation. Activities of malondialdehyde, superoxide dismutase, and glutathione peroxidase were also determined. Viability and apoptosis of RPTECs were measured using MTT assay and Guava Nexin assay, respectively. qRT-PCR was performed to determine the expressions of Bax, Bcl-2, nuclear factor kappa B (IκBα), and p65. Protein levels of Bax, Bcl-2, IκBα, p65, c-Jun N-terminal kinase, extracellular regulated protein kinases, and p38 were analyzed using western blotting. We found that BAI reduced inflammation and oxidative stress in vivo and in vitro. Moreover, BAI alleviated the LPS-induced RPTECs viability inhibition and apoptosis enhancement, as well as nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) activation. Phorbol ester, an activator of NF-κB, attenuated the effects of BAI on LPS-induced inflammatory cytokine expressions in RPTECs. In conclusion, BAI had anti-inflammatory and anti-oxidative effects on TIN patients and LPS-induced RPTECs by down-regulating NF-κB and MAPK pathways.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Young Adult , NF-kappa B/metabolism , Flavanones/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Nephritis, Interstitial/drug therapy , Antioxidants/administration & dosage , Enzyme-Linked Immunosorbent Assay , Signal Transduction/drug effects , Down-Regulation , Lipopolysaccharides , NF-kappa B/drug effects , MAP Kinase Signaling System/drug effects
10.
Biol. Res ; 51: 17, 2018. graf
Article in English | LILACS | ID: biblio-950903

ABSTRACT

BACKGROUND: Improper control on reactive oxygen species (ROS) elimination process and formation of free radicals causes tissue dysfunction. Pineal hormone melatonin is considered a potent regulator of such oxidative damage in different vertebrates. Aim of the current communication is to evaluate the levels of oxidative stress and ROS induced damage, and amelioration of oxidative status through melatonin induced activation of signaling pathways. Hepatocytes were isolated from adult Labeo rohita and exposed to H2O2 at three different doses (12.5, 25 and 50 µM) to observe peroxide induced damage in fish hepatocytes. Melatonin (25, 50 and 100 µg/ml) was administered against the highest dose of H2O2. Enzymatic and non-enzymatic antioxidants such as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) was measured spectrophotometrically. Expression level of heat shock proteins (HSP70 and HSP90), HSPs-associated signaling molecules (Akt, ERK, cytosolic and nuclear NFkB), and melatonin receptor was also measured by western blotting analysis. RESULTS: H2O2 induced oxidative stress significantly altered (P < 0.05) MDA and GSH level, SOD and CAT activity, and up regulated HSP70 and HSP90 expression in carp hepatocytes. Signaling proteins exhibited differential modulation as revealed from their expression patterns in H2O2-exposed fish hepatocytes, in comparison with control hepatocytes. Melatonin treatment of H2O2-stressed fish hepatocytes restored basal cellular oxidative status in a dose dependent manner. Melatonin was observed to be inducer of signaling process by modulation of signaling molecules and melatonin receptor. CONCLUSIONS: The results suggest that exogenous melatonin at the concentration of 100 µg/ml is required to improve oxidative status of the H2O2-stressed fish hepatocytes. In H2O2 exposed hepatocytes, melatonin modulates expression of HSP70 and HSP90 that enable the hepatocytes to become stress tolerant and survive by altering the actions of ERK, Akt, cytosolic and nuclear NFkB in the signal transduction pathways. Study also confirms that melatonin could act through melatonin receptor coupled to ERK/Akt signaling pathways. This understanding of the mechanism by which melatonin regulates oxidative status in the stressed hepatocytes may initiate the development of novel strategies for hepatic disease therapy in future.


Subject(s)
Animals , Signal Transduction/drug effects , Oxidative Stress/drug effects , Hepatocytes/drug effects , Hydrogen Peroxide/pharmacology , Melatonin/pharmacology , Spectrophotometry , Superoxide Dismutase/drug effects , Catalase/drug effects , Catalase/metabolism , Blotting, Western , NF-kappa B/drug effects , NF-kappa B/metabolism , Reactive Oxygen Species/metabolism , MAP Kinase Signaling System/drug effects , Hepatocytes/metabolism , Proto-Oncogene Proteins c-akt/drug effects , Fishes , Glutathione/drug effects , Glutathione/metabolism , Malondialdehyde/metabolism
11.
Pakistan Journal of Pharmaceutical Sciences. 2017; 30 (1): 43-48
in English | IMEMR | ID: emr-185738

ABSTRACT

In this study we investigated the anti-inflammatory effects and mechanisms of Hizikia fusiformis [HF] extracts in lipopolysaccharide [LPS]-induced RAW 264.7 cells. We extracted HF using solvent and sub-critical water techniques. In results, HF extracts inhibited nitric oxide [NO] production in cell-free and LPS-stimulated RAW 264.7 cells. HF210 [extract prepared with sub critical water at 210[degree]C] was most effective. The HF210 extract dose-dependently inhibited inducible nitric oxide synthase expression [iNOS] and nuclear factor kappa [NF-kB] p65 translocation from cytosol to the nucleus. Furthermore, HF210 extract dose-dependently inhibited the phosphorylation of p38 mitogen-activated protein kinase [p38 MAPK], Jun N-terminal kinase [JNK], and signal transducers and activators of transcription [STAT]-1in LPS-induced RAW 264.7 cells. Thus, our results suggest that anti-inflammatory effects of HF210 extract showed a noticeable distinction by regulation of multiple signaling pathways in LPS-induced RAW 264.7 cells


Subject(s)
Phaeophyta , Plant Extracts , NF-kappa B/drug effects , Macrophages/drug effects , RAW 264.7 Cells/drug effects , Signal Transduction , Lipopolysaccharides/pharmacology
12.
Braz. j. med. biol. res ; 50(4): e5714, 2017. tab, graf
Article in English | LILACS | ID: biblio-839285

ABSTRACT

Inflammation of cartilage is a primary symptom for knee-joint osteoarthritis. Matrix metalloproteinases (MMPs) are known to play an important role in the articular cartilage destruction related to osteoarthritis. Naringenin is a plant-derived flavonoid known for its anti-inflammatory properties. We studied the effect of naringenin on the transcriptional expression, secretion and enzymatic activity of MMP-3 in vivo in the murine monosodium iodoacetate (MIA) osteoarthritis model. The assessment of pain behavior was also performed in the MIA rats. The destruction of knee-joint tissues was analyzed microscopically. Moreover, the effect of naringenin was also studied in vitro in IL-1β activated articular chondrocytes. The transcriptional expression of MMP-3, MMP-1, MMP-13, thrombospondin motifs (ADAMTS-4) and ADAMTS-5 was also studied in primary cultured chondrocytes of rats. Naringenin caused significant reduction in pain behavior and showed marked improvement in the tissue morphology of MIA rats. Moreover, a significant inhibition of MMP-3 expression in MIA rats was observed upon treatment with naringenin. In the in vitro tests, naringenin caused a significant reduction in the transcriptional expression, secretion and enzymatic activity of the studied degradative enzymes. The NF-κB pathway was also found to be inhibited upon treatment with naringenin in vitro. Overall, the study suggests that naringenin alleviated pain and regulated the production of matrix-metalloproteinases via regulation of NF-κB pathway. Thus, naringenin could be a potent therapeutic option for the treatment of osteoarthritis.


Subject(s)
Animals , Male , Anti-Inflammatory Agents/pharmacology , Arthralgia/enzymology , Chondrocytes/enzymology , Flavanones/pharmacology , Knee Joint/enzymology , Matrix Metalloproteinase 3/biosynthesis , Osteoarthritis, Knee/enzymology , Arthralgia/drug therapy , Blotting, Western , Cell Proliferation/drug effects , Cells, Cultured , Chondrocytes/drug effects , Disease Models, Animal , Gene Expression , Interleukin-1beta/analysis , Interleukin-1beta/drug effects , Interleukin-1beta/metabolism , Knee Joint/pathology , Matrix Metalloproteinase 3/analysis , NF-kappa B/analysis , NF-kappa B/drug effects , NF-KappaB Inhibitor alpha/analysis , NF-KappaB Inhibitor alpha/drug effects , Osteoarthritis, Knee/drug therapy , Osteoarthritis, Knee/pathology , Random Allocation , Rats, Wistar , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction , Time Factors , Treatment Outcome
13.
Braz. j. med. biol. res ; 49(12): e5717, 2016. graf
Article in English | LILACS | ID: biblio-828174

ABSTRACT

Propofol is one of the most commonly used intravenous anesthetic agents during cancer resection surgery. A previous study has found that propofol can inhibit invasion and induce apoptosis of ovarian cancer cells. However, the underlying mechanisms are not known. miR-9 has been reported to be little expressed in ovarian cancer cells, which has been related to a poor prognosis in patients with ovarian cancer. Studies have also demonstrated that propofol could induce microRNAs expression and suppress NF-κB activation in some situations. In the present study, we assessed whether propofol inhibits invasion and induces apoptosis of ovarian cancer cells by miR-9/NF-κB signaling. Ovarian cancer ES-2 cells were transfected with anti-miR-9 or p65 cDNA or p65 siRNA for 24 h, after which the cells were treated with different concentrations of propofol (1, 5, and 10 μg/mL) for 24 h. Cell growth and apoptosis were detected using MTT assay and flow cytometry analysis. Cell migration and invasion were detected using Transwell and Wound-healing assay. Western blot and electrophoretic mobility shift assay were used to detect different protein expression and NF-κB activity. Propofol inhibited cell growth and invasion, and induced cell apoptosis in a dose-dependent manner, which was accompanied by miR-9 activation and NF-κB inactivation. Knockdown of miR-9 abrogated propofol-induced NF-κB activation and MMP-9 expression, reversed propofol-induced cell death and invasion of ES-2 cells. Knockdown of p65 inhibited NF-κB activation rescued the miR-9-induced down-regulation of MMP-9. In addition, overexpression of p65 by p65 cDNA transfection increased propofol-induced NF-κB activation and reversed propofol-induced down-regulation of MMP-9. Propofol upregulates miR-9 expression and inhibits NF-κB activation and its downstream MMP-9 expression, leading to the inhibition of cell growth and invasion of ES-2 cells.


Subject(s)
Humans , Female , MicroRNAs/drug effects , Neoplasm Invasiveness/prevention & control , NF-kappa B/drug effects , Ovarian Neoplasms/drug therapy , Propofol/therapeutic use , Protective Agents/therapeutic use , Apoptosis/drug effects , Blotting, Western , Down-Regulation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Matrix Metalloproteinase 9/metabolism , MicroRNAs/genetics , NF-kappa B/metabolism , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Polymerase Chain Reaction
14.
Braz. j. med. biol. res ; 48(7): 654-664, 07/2015. graf
Article in English | LILACS | ID: lil-751344

ABSTRACT

Recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) may influence asthma pathogenesis; however, its roles in regulating specific molecular transcription mechanisms remain unclear. We aimed to investigate the effect of 1,25(OH)2D3 on the expression and enzyme activity of histone deacetylase 2 (HDAC2) and its synergistic effects with dexamethasone (Dx) in the inhibition of inflammatory cytokine secretion in a rat asthma model. Healthy Wistar rats were randomly divided into 6 groups: control, asthma, 1,25(OH)2D3 pretreatment, 1,25(OH)2D3 treatment, Dx treatment, and Dx and 1,25(OH)2D3 treatment. Pulmonary inflammation was induced by ovalbumin (OVA) sensitization and challenge (OVA/OVA). Inflammatory cells and cytokines in the bronchoalveolar lavage (BAL) fluid and histological changes in lung tissue were examined. Nuclear factor kappa B (NF-κB) p65 and HDAC2 expression levels were assessed with Western blot analyses and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Enzyme activity measurements and immunohistochemical detection of HDAC2 were also performed. Our data demonstrated that 1,25(OH)2D3 reduced the airway inflammatory response and the level of inflammatory cytokines in BAL. Although NF-κB p65 expression was attenuated in the pretreatment and treatment groups, the expression and enzyme activity of HDAC2 were increased. In addition, 1,25(OH)2D3 and Dx had synergistic effects on the suppression of total cell infusion, cytokine release, and NF-κB p65 expression, and they also increased HDAC2 expression and activity in OVA/OVA rats. Collectively, our results indicated that 1,25(OH)2D3 might be useful as a novel HDAC2 activator in the treatment of asthma.


Subject(s)
Animals , Male , Asthma/drug therapy , Calcitriol/pharmacology , /drug effects , NF-kappa B/drug effects , Vitamins/pharmacology , Asthma/chemically induced , Blotting, Western , Bronchoalveolar Lavage Fluid/chemistry , Cell Count , Calcitriol/therapeutic use , Cytokines/analysis , Cytokines/drug effects , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Gene Expression Regulation, Enzymologic/drug effects , /metabolism , Immunohistochemistry , Lung/chemistry , Lung/drug effects , NF-kappa B/analysis , Ovalbumin , Rats, Wistar , Real-Time Polymerase Chain Reaction , Reproducibility of Results , Treatment Outcome , Vitamins/therapeutic use
15.
Acta cir. bras ; 30(6): 430-438, 06/2015. tab, graf
Article in English | LILACS | ID: lil-749640

ABSTRACT

PURPOSE: To examine the effects of the oil mixes (ω-9, ω-6 and ω-3) in rats subjected to thermal burn. It was also aimed to assess whether the sources of ω3 would interfere with the effect of such mixes on the thermal injury. METHODS: Thirty-six rats distributed into five groups: burned + water, burned + isolipid mix, burned + oil mix 1 (ALA), burned + oil mix 2 (ALA + EPA + DHA of fish) and burned + oil mix 3 (ALA + DHA from seaweed). The thermal injury was involving total thickness of skin. After the burns animals received the oil mixes for seven days. The lesions were evaluated by immunohistochemistry. RESULTS: Animals receiving mix 3 showed a smaller extension of the thermal injury as compared to those that were supplemented with other oils mixes. Expression of Ki-67 in the receiving Mix 3 increased as compared to all the other groups. Animals supplemented with mix 3 were able to inhibit NF-κB in injured tissue. CONCLUSION: Rats received oil mix in which the source of ω3 (ALA+DHA of seaweed) showed inhibition of NF-κB, increase in cell proliferation, and reduction the extension of thermal lesion. .


Subject(s)
Animals , Male , Burns/drug therapy , Fatty Acids/pharmacology , /drug effects , NF-kappa B/drug effects , Seaweed/chemistry , Burns/pathology , Cell Proliferation/drug effects , Drug Combinations , /pharmacology , /therapeutic use , /pharmacology , /therapeutic use , Immunohistochemistry , /analysis , NF-kappa B/analysis , Random Allocation , Rats, Wistar , Reproducibility of Results , Time Factors , Treatment Outcome
16.
Braz. j. med. biol. res ; 48(4): 286-291, 4/2015. tab, graf
Article in English | LILACS | ID: lil-744366

ABSTRACT

This study aimed to determine the effects of different concentrations of propofol (2,6-diisopropylphenol) on lipopolysaccharide (LPS)-induced expression and release of high-mobility group box 1 protein (HMGB1) in mouse macrophages. Mouse macrophage cell line RAW264.7 cells were randomly divided into 5 treatment groups. Expression levels of HMGB1 mRNA were detected using RT-PCR, and cell culture supernatant HMGB1 protein levels were detected using enzyme-linked immunosorbent assay (ELISA). Translocation of HMGB1 from the nucleus to the cytoplasm in macrophages was observed by Western blotting and activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus was detected using ELISA. HMGB1 mRNA expression levels increased significantly in the cell culture supernatant and in cells after 24 h of stimulating RAW264.7 cells with LPS (500 ng/mL). However, HMGB1 mRNA expression levels in the P2 and P3 groups, which received 500 ng/mL LPS with 25 or 50 μmol/mL propofol, respectively, were significantly lower than those in the group receiving LPS stimulation (P<0.05). After stimulation by LPS, HMGB1 protein levels were reduced significantly in the nucleus but were increased in the cytoplasm (P<0.05). Simultaneously, the activity of NF-κB was enhanced significantly (P<0.05). After propofol intervention, HMGB1 translocation from the nucleus to the cytoplasm and NF-κB activity were inhibited significantly (each P<0.05). Thus, propofol can inhibit the LPS-induced expression and release of HMGB1 by inhibiting HMGB1 translocation and NF-κB activity in RAW264.7 cells, suggesting propofol may be protective in patients with sepsis.


Subject(s)
Animals , Mice , Anesthetics, Intravenous/pharmacology , Cell Nucleus/drug effects , HMGB1 Protein/drug effects , Macrophages/drug effects , Propofol/pharmacology , RNA, Messenger/drug effects , Active Transport, Cell Nucleus , Anesthetics, Intravenous/administration & dosage , Blotting, Western , Cell Line , Cell Nucleus/metabolism , Enzyme-Linked Immunosorbent Assay , Gene Expression/drug effects , HMGB1 Protein/genetics , HMGB1 Protein/metabolism , Lipopolysaccharides , Macrophages/metabolism , NF-kappa B/drug effects , NF-kappa B/metabolism , Propofol/administration & dosage , Random Allocation , Real-Time Polymerase Chain Reaction , RNA, Messenger/metabolism
17.
Gut and Liver ; : 411-416, 2015.
Article in English | WPRIM | ID: wpr-142461

ABSTRACT

BACKGROUND/AIMS: To investigate the expression of Toll-like receptor 4 (TLR4) in the pancreases of rats with acute necrotizing pancreatitis (ANP) and any changes upon treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappaB (NF-kappaB), as well as to determine the relationship between TLR4 and NF-kappaB in ANP pathogenesis. METHODS: A total of 72 SD rats were randomly divided into three groups, namely, the control (sham-operation), ANP, and ANP with PDTC pretreatment groups. The PDTC-pretreated group was intraperitoneally injected with PDTC at a dose of 100 mg/kg 1 hour before the induction of ANP. The expressions of TLR4 and NF-kappaB in pancreatic tissue were evaluated by immunohistochemistry and Western blot analysis. The mRNA levels of cytokines tumor necrosis factor alpha, interleukin (IL)-1beta, and IL-6 were measured by reverse transcription polymerase chain reaction. RESULTS: The expressions of TLR4, NF-kappaB, and cytokine (NF-kappaB target) genes in the pancreatic tissue increased more significantly in the ANP groups than in the sham-operation group at 3, 6, and 12 hours. Pretreatment with PDTC alleviated the inflammatory activation in the pancreas with ANP, causing a significant decrease in the expressions of TLR4, NF-kappaB, and cytokine genes in the pancreatic tissue. CONCLUSIONS: The expressions of TLR4 and NF-kappaB were increased in the pancreases of rats with ANP. PDTC not only inhibits NF-kappaB but also suppresses the expression of TLR4 and downregulates the expression of the related cytokine genes.


Subject(s)
Animals , Antioxidants/pharmacology , Interleukin-1beta/genetics , Interleukin-6/genetics , Male , NF-kappa B/drug effects , Pancreas/metabolism , Pancreatitis, Acute Necrotizing/chemically induced , Pyrrolidines/pharmacology , RNA, Messenger/metabolism , Random Allocation , Rats , Rats, Sprague-Dawley , Thiocarbamates/pharmacology , Toll-Like Receptor 4/drug effects , Tumor Necrosis Factor-alpha/genetics
18.
Gut and Liver ; : 411-416, 2015.
Article in English | WPRIM | ID: wpr-142460

ABSTRACT

BACKGROUND/AIMS: To investigate the expression of Toll-like receptor 4 (TLR4) in the pancreases of rats with acute necrotizing pancreatitis (ANP) and any changes upon treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappaB (NF-kappaB), as well as to determine the relationship between TLR4 and NF-kappaB in ANP pathogenesis. METHODS: A total of 72 SD rats were randomly divided into three groups, namely, the control (sham-operation), ANP, and ANP with PDTC pretreatment groups. The PDTC-pretreated group was intraperitoneally injected with PDTC at a dose of 100 mg/kg 1 hour before the induction of ANP. The expressions of TLR4 and NF-kappaB in pancreatic tissue were evaluated by immunohistochemistry and Western blot analysis. The mRNA levels of cytokines tumor necrosis factor alpha, interleukin (IL)-1beta, and IL-6 were measured by reverse transcription polymerase chain reaction. RESULTS: The expressions of TLR4, NF-kappaB, and cytokine (NF-kappaB target) genes in the pancreatic tissue increased more significantly in the ANP groups than in the sham-operation group at 3, 6, and 12 hours. Pretreatment with PDTC alleviated the inflammatory activation in the pancreas with ANP, causing a significant decrease in the expressions of TLR4, NF-kappaB, and cytokine genes in the pancreatic tissue. CONCLUSIONS: The expressions of TLR4 and NF-kappaB were increased in the pancreases of rats with ANP. PDTC not only inhibits NF-kappaB but also suppresses the expression of TLR4 and downregulates the expression of the related cytokine genes.


Subject(s)
Animals , Antioxidants/pharmacology , Interleukin-1beta/genetics , Interleukin-6/genetics , Male , NF-kappa B/drug effects , Pancreas/metabolism , Pancreatitis, Acute Necrotizing/chemically induced , Pyrrolidines/pharmacology , RNA, Messenger/metabolism , Random Allocation , Rats , Rats, Sprague-Dawley , Thiocarbamates/pharmacology , Toll-Like Receptor 4/drug effects , Tumor Necrosis Factor-alpha/genetics
19.
Biol. Res ; 47: 1-8, 2014. graf
Article in English | LILACS | ID: biblio-950737

ABSTRACT

BACKGROUND: The root of Angelica sinensis (AS), also known as "Dang-gui," was a popular herbal medicine widely used in the treatment of gynecological diseases in China, Korea, and Japan for a long time. This study aimed to determine the effects of ethyl acetate fraction from Angelica sinensis (EAAS) on the interleukin-1ß (IL-1ß)-induced proliferation of rheumatoid arthritis synovial fibroblasts (RASFs), and production of matrix metalloproteinases (MMPs), cyclooxygenase (COX) 2, and prostaglandin E2 (PGE2), involved in articular bone and cartilage destruction, by RASFs. RESULTS: RASF proliferation was evaluated with cholecystokinin octapeptide (CCK-8) reagent in the presence of IL-1ß with/without EAAS. Expression of MMPs, tissue inhibitor of metalloproteinases-1 (TIMP-1), COXs, PGE2, and intracellular mitogen-activated protein kinase (MAPK) signaling molecules, including p-ERK, p-p38, p-JNK, and NF-κB, were examined using immunoblotting or semi-quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. EAAS inhibited IL-1ß-induced RASF proliferation; MMP-1, MMP-3, and COX-2 mRNA and protein expressions; and PGE2 production. EAAS also inhibits the phosphorylation of ERK-1/2, p38, and JNK, and activation of NF-κB by IL-1ß. CONCLUSION: EAAS might be a new therapeutic modality for rheumatoid arthritis management.


Subject(s)
Humans , Arthritis, Rheumatoid/metabolism , Bursa, Synovial/cytology , Inflammation Mediators/metabolism , Angelica sinensis/chemistry , Cell Proliferation/drug effects , Fibroblasts/drug effects , Arthritis, Rheumatoid/pathology , Recombinant Proteins/pharmacology , Enzyme-Linked Immunosorbent Assay , Plant Extracts/pharmacology , Dinoprostone/metabolism , Immunoblotting , NF-kappa B/drug effects , Plant Roots/chemistry , Matrix Metalloproteinases/drug effects , Matrix Metalloproteinases/metabolism , Herbal Medicine , Cyclooxygenase 2/drug effects , Cyclooxygenase 2/metabolism , Interleukin-1beta/pharmacology , Primary Cell Culture , Real-Time Polymerase Chain Reaction , Fibroblasts/cytology , Fibroblasts/metabolism , Flow Cytometry , Knee Joint/cytology , Acetates
20.
Braz. j. med. biol. res ; 46(8): 659-669, ago. 2013. graf
Article in English | LILACS | ID: lil-684523

ABSTRACT

Chronic inflammation induced by amyloid-beta (Aβ) plays a key role in the development of age-related macular degeneration (AMD), and matrix metalloproteinase-9 (MMP-9), interleukin (IL)-6, and IL-8 may be associated with chronic inflammation in AMD. Sirtuin 1 (SIRT1) regulates inflammation via inhibition of nuclear factor-kappa B (NF-κB) signaling, and resveratrol has been reported to prevent Aβ-induced retinal degeneration; therefore, we investigated whether this action was mediated via activation of SIRT1 signaling. Human adult retinal pigment epithelial (RPE) cells were exposed to Aβ, and overactivation and knockdown of SIRT1 were performed to investigate whether SIRT1 is required for abrogating Aβ-induced inflammation. We found that Aβ-induced RPE barrier disruption and expression of IL-6, IL-8, and MMP-9 were abrogated by the SIRT1 activator SRT1720, whereas alterations induced by Aβ in SIRT1-silenced RPE cells were not attenuated by SRT1720. In addition, SRT1720 inhibited Aβ-mediated NF-κB activation and decrease of the NF-κB inhibitor, IκBα. Our findings suggest a protective role for SIRT1 signaling in Aβ-dependent retinal degeneration and inflammation in AMD.


Subject(s)
Adult , Humans , Amyloid beta-Peptides/metabolism , Inflammation/chemically induced , Macular Degeneration/prevention & control , NF-kappa B/metabolism , Retinal Pigment Epithelium/drug effects , Signal Transduction/physiology , Sirtuin 1/physiology , Antioxidants/pharmacology , Blood-Retinal Barrier/physiopathology , Cell Survival/drug effects , Enzyme Assays/methods , Gene Silencing , /pharmacology , /metabolism , /metabolism , Macular Degeneration/chemically induced , Macular Degeneration/physiopathology , Matrix Metalloproteinase 9/metabolism , NF-kappa B/drug effects , Primary Cell Culture , Real-Time Polymerase Chain Reaction , RNA Interference , Retinal Pigment Epithelium/metabolism , Stilbenes/pharmacology
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