Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 559
Filter
1.
Article in English | WPRIM | ID: wpr-878318

ABSTRACT

Objective@#Antimony (Sb) has recently been identified as a novel nerve poison, although the cellular and molecular mechanisms underlying its neurotoxicity remain unclear. This study aimed to assess the effects of the nuclear factor kappa B (NF-κB) signaling pathway on antimony-induced astrocyte activation.@*Methods@#Protein expression levels were detected by Western blotting. Immunofluorescence, cytoplasmic and nuclear fractions separation were used to assess the distribution of p65. The expression of protein in brain tissue sections was detected by immunohistochemistry. The levels of mRNAs were detected by Quantitative real-time polymerase chain reaction (qRT-PCR) and reverse transcription-polymerase chain reaction (RT-PCR).@*Results@#Antimony exposure triggered astrocyte proliferation and increased the expression of two critical protein markers of reactive astrogliosis, inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP), indicating that antimony induced astrocyte activation @*Conclusion@#Antimony activated astrocytes by activating the NF-κB signaling pathway.


Subject(s)
Animals , Antimony/toxicity , Astrocytes/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Glial Fibrillary Acidic Protein/metabolism , MAP Kinase Kinase Kinases , Male , Mice, Inbred ICR , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/metabolism , Rats , Signal Transduction/drug effects
2.
Article in Chinese | WPRIM | ID: wpr-828426

ABSTRACT

Three bibenzyls 1-3 and six other compounds 4-9 were firstly isolated from Dendrobium huoshanense stems. They were identified as 3',4-dihydroxy-3,5'-dimethoxybibenzyl(1), batatasin Ⅲ(2), 3,4'-dihydroxy-5-methoxy bibenzyl(3), dihydroconiferyl dihydro-p-coumarate(4), syringaresinol(5), 3-(4-hydroxyphenyl)-propionic acid ethyl ester(6),(3-ethylphenyl)-1,2-ethanediol(7),(S)-5-hydroxy-3,4-dimethyl-5-pentylfuran-2(5H)-one(8) and loliolide(9). Anti-inflammation assay showed that bibenzyls 1-3 could significantly inhibit the production of nitric oxide(NO) and the expression of tumor necrosis factor α(TNF-α) and interleukin 1β(IL-1β) mRNA in LPS-induced RAW264.7 macrophages. Mechanism study exhibited that the phosphorylation of nuclear factor kappa B(NF-κB) p65, inhibitor of κB(IκB), extracellular regulatedprotein kinase(ERK), c-Jun N-terminalkinase(JNK), p38 and Akt of LPS-induced RAW264.7 macrophages could be remarkably reduced by 1. These results suggested that the inflammatory response of LPS-induced RAW264.7 macrophages could be significantly inhibited by 1-3. Additionally, the anti-inflammatory effect of 1 might be contributed to its ability on the regulation of NF-κB, MAPKs and Akt signaling pathways.


Subject(s)
Anti-Inflammatory Agents , Therapeutic Uses , Dendrobium , Humans , Inflammation , Drug Therapy , Lipopolysaccharides , Macrophages , NF-kappa B , Nitric Oxide , Nitric Oxide Synthase Type II
3.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 41(5): 419-427, Sept.-Oct. 2019. tab, graf
Article in English | LILACS | ID: biblio-1039115

ABSTRACT

Objective: To evaluate whether an animal model of mania induced by lisdexamfetamine dimesylate (LDX) has an inflammatory profile and whether immune activation by lipopolysaccharides (LPS) has a cumulative effect on subsequent stimuli in this model. We also evaluated the action of lithium (Li) on inflammatory and neurotrophic factors. Methods: Adult male Wistar rats were subjected to an animal model of mania. After the open-field test, they were given LPS to induce systemic immune activation. Subsequently, the animals' blood was collected, and their serum levels of brain-derived neurotrophic factor and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1β, IL-10, and inducible nitric oxide synthase [iNOS]) were measured. Results: LDX induced hyperactivity in the animals, but no inflammatory marker levels increased except brain-derived neurotrophic factor (BDNF). Li had no effect on serum BDNF levels but prevented iNOS levels from increasing in animals subjected to immune activation. Conclusion: Although Li prevented an LPS-induced increase in serum iNOS levels, its potential anti-inflammatory effects in this animal model of mania were conflicting.


Subject(s)
Animals , Male , Bipolar Disorder/immunology , Disease Models, Animal , Lisdexamfetamine Dimesylate , Lithium/pharmacology , Anti-Inflammatory Agents/pharmacology , Nerve Growth Factors/drug effects , Time Factors , Bipolar Disorder/physiopathology , Bipolar Disorder/chemically induced , Enzyme-Linked Immunosorbent Assay , Lipopolysaccharides/pharmacology , Reproducibility of Results , Cytokines/blood , Treatment Outcome , Rats, Wistar , Brain-Derived Neurotrophic Factor/blood , Nitric Oxide Synthase Type II/blood , Locomotion/drug effects
4.
Article in English | WPRIM | ID: wpr-785903

ABSTRACT

Macrophages play essential roles in innate immune responses by producing various immune mediators. Therefore, modulating macrophage function is an attractive strategy to treat immune disorders. Aralia cordata var. continentalis (AC), known as “Dokwhal” in Korea, possesses various biological and medicinal functions, including immunomodulation. The present study investigated the effect of the hot water extract of AC (HAC) on RAW264.7 murine macrophages. When these cells were treated with HAC, nitric oxide production and inducible nitric oxide synthase expression was induced dose-dependently. In addition, HAC treatment triggered the secretion of innate immune cytokines, such as TNF-α and IL-6. Phagocytosis, measured by FITC-dextran internalization showed that HAC stimulated the phagocytic activity of macrophages. Furthermore, HAC promoted the production of reactive oxygen species in RAW264.7 cells, determined by CM-H2DCFDA. In addition, the immunoblot analysis of intracellular signaling proteins revealed that NF-kB and MAPK signaling pathways, which are important signaling mediators of inflammation, are upregulated by HAC. In conclusion, these findings suggested that HAC can stimulate macrophage activity, and NF-kB and MAPK signaling pathways might be involved in the immunostimulatory effects of HAC.


Subject(s)
Aralia , Cytokines , Immune System Diseases , Immunity, Innate , Immunomodulation , Inflammation Mediators , Interleukin-6 , Intracellular Signaling Peptides and Proteins , Korea , Macrophages , NF-kappa B , Nitric Oxide , Nitric Oxide Synthase Type II , Phagocytosis , Reactive Oxygen Species , Water
5.
Article in English | WPRIM | ID: wpr-776908

ABSTRACT

The flower buds of Lonicera macranthoides (Shan Yin-Hua), represent an important traditional Chinese medicine and food ingredient. A phytochemical investigation of the 70% EtOH extract of the flower buds of L. macranthoides resulted in the isolation of 12 triterpenoids (1-12), including two new ursane-type nortriterpenes, 2α, 24-dihydroxy-23-nor-ursolic acid (1) and 2α, 4α-dihydroxy-23-nor-ursolic acid (2). Their structures were established by multiple spectroscopic methods and comparison with literature data. All isolated compounds were evaluated for their anti-inflammatory effects in LPS-activated RAW264.7 cells. Compounds 1 and 2 exhibited inhibitory effects on iNOS at the concentration of 30 μmol·L.


Subject(s)
Animals , Anti-Inflammatory Agents , Chemistry , Pharmacology , Drugs, Chinese Herbal , Chemistry , Enzyme Inhibitors , Chemistry , Pharmacology , Ethanol , Chemistry , Flowers , Chemistry , Lonicera , Chemistry , Macrophages , Metabolism , Mice , Molecular Structure , Nitric Oxide , Metabolism , Nitric Oxide Synthase Type II , Plant Extracts , Chemistry , Plants, Edible , Chemistry , Triterpenes , Chemistry , Pharmacology
6.
Article in English | WPRIM | ID: wpr-776865

ABSTRACT

In the present study, we investigated anti-inflammatory effect of Cardamine komarovii flower (CKF) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). We determined the effect of CKF methanolic extracts on LPS-induced pro-inflammatory mediators NO and prostaglandin E2 (PGE2), production of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6), and related protein expression levels of MyD88/TRIF signaling pathways in peritoneal macrophages (PMs). Nuclear translocation of NF-κB-p65 was analyzed by immunofluorescence. For the in vivo experiments, an ALI model was established to detect the number of inflammatory cells and inflammatory factors (IL-1β, TNF-α, and IL-6) in bronchoalveolar lavage fluid (BALF) of mice. The pathological damage in lung tissues was evaluated through H&E staining. Our results showed that CKF can decrease the production of inflammatory mediators, such as NO and PGE2, by inhibiting their synthesis-related enzymes iNOS and COX-2 in LPS-induced PMs. In addition, CKF can downregulate the mRNA levels of IL-1β, TNF-α, and IL-6 to inhibit the production of inflammatory factors. Mechanism studies indicated that CKF possesses a fine anti-inflammatory effect by regulating MyD88/TRIF dependent signaling pathways. Immunocytochemistry staining showed that the CKF extract attenuates the LPS-induced translocation of NF-kB p65 subunit in the nucleus from the cytoplasm. In vivo experiments revealed that the number of inflammatory cells and IL-1β in BALF of mice decrease after CKF treatment. Histopathological observation of lung tissues showed that CKF can remarkably improve alveolar clearance and infiltration of interstitial and alveolar cells after LPS stimulation. In conclusion, our results suggest that CKF inhibits LPS-induced inflammatory response by inhibiting the MyD88/TRIF signaling pathways, thereby protecting mice from LPS-induced ALI.


Subject(s)
Acute Lung Injury , Drug Therapy , Genetics , Metabolism , Adaptor Proteins, Vesicular Transport , Genetics , Metabolism , Animals , Anti-Inflammatory Agents , Chemistry , Cardamine , Chemistry , Cyclooxygenase 2 , Genetics , Metabolism , Female , Flowers , Chemistry , Humans , Lipopolysaccharides , Male , Mice , Myeloid Differentiation Factor 88 , Genetics , Metabolism , NF-kappa B , Genetics , Metabolism , Nitric Oxide Synthase Type II , Genetics , Metabolism , Plant Extracts , Chemistry , Signal Transduction , Tumor Necrosis Factor-alpha , Genetics , Metabolism
7.
Article in Chinese | WPRIM | ID: wpr-776512

ABSTRACT

OBJECTIVE@#To investigate the effects of vitamin E on the respiratory function impairment in rats with chronic obstructive pulmonary disease (COPD) after exposed to high temperature and PM.@*METHODS@#Fifty-four 7-week-old SPF male Wistar rats were randomly divided into 9 experimental groups (n=6). The rat COPD model was established by lipopolysaccharide (LPS) and smoke exposure. After modeled, the rats were tracheal instilled with PM (0 mg/ml, 3.2 mg/ml) and intraperitoneally injected with vitamin E at the dose of 40 mg/kg (20 mg/ml). Part of rats (high temperature groups) were then exposed to high temperature (40℃), once (8 h) a day for three consecutive days. After the last exposure, the lung function of rats was detected. The expression levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) were detected by corresponding ELISA kits.@*RESULTS@#Compared with the control group, exposure of high temperature and PM could inhibit the lung function of COPD rats significantly (P<0.05); the level of MCP-1 was increased significantly in PM-exposure groups (P<0.05); iNOS was increased significantly in the groups of high temperature (P<0.05). Compared with the single-PM exposure groups, TNF-α in lung was decreased in the normal temperature health group and high temperature COPD group (P<0.05) after treated with vitamin E; MCP-1 was decreased in all vitamin E-treated groups (P<0.05); the decreased iNOS only appeared in the group of high temperature with vitamin E treatment.@*CONCLUSION@#High temperature and PM could aggravate the inflammation of COPD rats. As an antioxidant, vitamin E may protect the lung from the damage effects.


Subject(s)
Animals , Chemokine CCL2 , Metabolism , Hot Temperature , Lung , Male , Nitric Oxide Synthase Type II , Metabolism , Particulate Matter , Pulmonary Disease, Chronic Obstructive , Drug Therapy , Random Allocation , Rats , Rats, Wistar , Tumor Necrosis Factor-alpha , Metabolism , Vitamin E , Pharmacology
8.
Article in English | WPRIM | ID: wpr-760621

ABSTRACT

BACKGROUND/OBJECTIVES: Excessive production of reactive oxygen species (ROS) such as hydroxyl (·OH), nitric oxide (NO), and hydrogen peroxide (H2O2) is reported to induce oxidative stress. ROS generated by oxidative stress can potentially damage glial cells in the nervous system. Cordyceps militaris (CM), a kind of natural herb widely found in East Asia. In this study, we investigated the free radical scavenging activity of the CM extract and its neuroprotective effects in H2O2-induced C6 glial cells. MATERIALS/METHODS: The ethanol extract of CM (100–1,000 µg/mL) was used to measure DPPH, ·OH, and NO radical scavenging activities. In addition, hydrogen peroxide (H2O2)-induced C6 glial cells were treated with CM at 0.5–2.5 µg/mL for measurement of cell viability, ROS production, and protein expression resulting from oxidative stress. RESULTS: The CM extract showed high scavenging activities against DPPH, ·OH, and NO radicals at concentration of 1,000 µg/mL. Treatment of CM with H2O2-induced oxidative stress in C6 glial cells significantly increased cell viability, and decreased ROS production. Cyclooxygenase-2 and inducible nitric oxide synthase protein expression was down-regulated in CM-treated groups. In addition, the protein expression level of phospho-p38 mitogen-activated protein kinase (p-p38 MAPK), phospho-c-Jun N-terminal kinase (p-JNK), and phospho-extracellular regulated protein kinases (p-ERK) in H2O2-induced C6 glial cells was down-regulated upon CM administration. CONCLUSION: CM exhibited radical scavenging activity and protective effect against H2O2 as indicated by the increased cell viability, decreased ROS production, down-regulation of inflammation-related proteins as well as p-p38, p-JNK, and p-ERK protein levels. Therefore, we suggest that CM could play the protective role from oxidative stress in glial cells.


Subject(s)
Cell Survival , Cordyceps , Cyclooxygenase 2 , Down-Regulation , Ethanol , Far East , Free Radicals , Hydrogen Peroxide , Hydrogen , In Vitro Techniques , Nervous System , Neuroglia , Neuroprotective Agents , Nitric Oxide , Nitric Oxide Synthase Type II , Oxidative Stress , Phosphotransferases , Protein Kinases , Reactive Oxygen Species
9.
Article in English | WPRIM | ID: wpr-760611

ABSTRACT

BACKGROUND/OBJECTIVES: Although aged black garlic has various biological activities such as anti-allergy, anti-inflammation and neuroprotection, effect of aged black garlic on chemically contact dermatitis is unclarified. MATERIALS/METHODS: To evaluate anti-dermatitic activity of aged black garlic extract, we investigated effects of a fraction of aged black garlic extract (BG10) on both in vivo and in vitro. RESULTS: BG10 almost inhibited formation of nitric monoxide and interleukin-6 (IL-6; IC50, 7.07 µg/mL) at 25 µg/mL, and dose-dependently reduced production of tumor necrosis factor-α (TNF-α; IC50, 52.07 µg/mL) and prostaglandin E2 (IC50, 38.46 µg/mL) in lipopolysaccharide-stimulated RAW264.7 cells. In addition, BG10 significantly inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2 and nuclear NF-κB, and improved that of cytosolic levels of NF-κB and IκBα in the cells. Consistent with in vitro studies, BG10 (0.5 mg/mL) not only reduced ear edema but also suppressed the formation of IL-6 and TNF-α induced by 12-O-tetradecanoylphorbol-13-acetate in ear tissues of mice. CONCLUSIONS: These findings suggest BG10 has anti-dermatitic activity through inhibiting activation of macrophages. Therefore, such effects of BG10 may provide information for the application of aged black garlic for prevention and therapy of contact dermatitis.


Subject(s)
Animals , Cyclooxygenase 2 , Cytokines , Cytosol , Dermatitis , Dermatitis, Contact , Dinoprostone , Ear , Edema , Garlic , In Vitro Techniques , Inhibitory Concentration 50 , Interleukin-6 , Macrophages , Mice , Necrosis , Neuroprotection , NF-kappa B , Nitric Oxide Synthase Type II
10.
Article in English | WPRIM | ID: wpr-764037

ABSTRACT

The purpose of this study was to evaluate the effect of mangosteen extract complex (MEC; Garcinia mangostana L. and propolis extracts) on the inhibition of inflammation and prevention of alveolar bone loss using a ligature-induced periodontitis model. Rat molars were ligatured with silk, and 1 µg/mL of lipopolysaccharide of Porphyromonas gingivalis was injected into the buccal and palatal gingivae of the teeth with or without treatment with the MEC. Changes in the expression levels of prostaglandin E₂ (PGE₂), interleukin-8 (IL-8), inducible nitric oxide synthase (iNOS), matrix metalloproteinase-8 (MMP-8), cyclooxygenase (COX)-1, and COX-2 in gingival tissues were evaluated using enzyme-linked immunosorbent assays. Alveolar bone loss around the ligated molars was examined using micro-computed tomography. The expression levels of PGE₂, IL-8, iNOS, MMP-8, COX-1, and COX-2 in gingival tissues were significantly reduced in the group treated with a mixture of 16 µg of mangosteen extract powder and 544 µg of propolis extract powder (ligation [Lig] + lipopolysaccharide extracted from P. gingivalis KCOM 2804 [L] + MEC 1:34). Additionally, alveolar bone loss was significantly reduced in the Lig + L + MEC 1:34 group compared with that in other groups. These results indicate that the MEC could be useful in preventing and treating periodontitis.


Subject(s)
Alveolar Bone Loss , Animals , Enzyme-Linked Immunosorbent Assay , Garcinia mangostana , Garcinia , Gingiva , Inflammation , Interleukin-8 , Matrix Metalloproteinase 8 , Molar , Nitric Oxide Synthase Type II , Periodontitis , Porphyromonas gingivalis , Propolis , Prostaglandin-Endoperoxide Synthases , Rats , Silk , Tooth
11.
Experimental Neurobiology ; : 516-528, 2019.
Article in English | WPRIM | ID: wpr-763776

ABSTRACT

We have previously demonstrated that the neurosteroid dehydroepiandrosterone sulfate (DHEAS) induces functional potentiation of N-methyl-D-aspartate (NMDA) receptors via increases in phosphorylation of NMDA receptor GluN1 subunit (pGluN1). However, the modulatory mechanisms responsible for the expression of the DHEA-synthesizing enzyme, cytochrome P450c17 following peripheral nerve injury have yet to be examined. Here we determined whether oxidative stress induced by the spinal activation of nitric oxide synthase type II (NOS-II) modulates the expression of P450c17 and whether this process contributes to the development of neuropathic pain in rats. Chronic constriction injury (CCI) of the sciatic nerve induced a significant increase in the expression of NOS-II in microglial cells and NO levels in the lumbar spinal cord dorsal horn at postoperative day 5. Intrathecal administration of the NOS-II inhibitor, L-NIL during the induction phase of neuropathic pain (postoperative days 0~5) significantly reduced the CCI-induced development of mechanical allodynia and thermal hyperalgesia. Sciatic nerve injury increased the expression of PKC- and PKA-dependent pGluN1 as well as the mRNA and protein levels of P450c17 in the spinal cord at postoperative day 5, and these increases were suppressed by repeated administration of L-NIL. Co-administration of DHEAS together with L-NIL restored the development of neuropathic pain and pGluN1 that were originally inhibited by L-NIL administration alone. Collectively these results provide strong support for the hypothesis that activation of NOS-II increases the mRNA and protein levels of P450c17 in the spinal cord, ultimately leading to the development of central sensitization and neuropathic pain induced by peripheral nerve injury.


Subject(s)
Animals , Central Nervous System Sensitization , Constriction , Cytochromes , Dehydroepiandrosterone , Dehydroepiandrosterone Sulfate , Hyperalgesia , N-Methylaspartate , Neuralgia , Nitric Oxide Synthase Type II , Nitric Oxide Synthase , Nitric Oxide , Oxidative Stress , Peripheral Nerve Injuries , Phosphorylation , Rats , RNA, Messenger , Rodentia , Sciatic Nerve , Spinal Cord , Spinal Cord Dorsal Horn
12.
Experimental Neurobiology ; : 352-361, 2019.
Article in English | WPRIM | ID: wpr-763769

ABSTRACT

Neuroinflammation is one of the key mechanisms of neuropathic pain, which is primarily mediated by the Toll-like receptor 4 (TLR4) signaling pathways in microglia. Therefore, TLR4 may be a reasonable target for treatment of neuropathic pain. Here, we examined the analgesic effect of TLR4 antagonistic peptide 2 (TAP2) on neuropathic pain induced by spinal nerve ligation in rats. When lipopolysaccharide (LPS)-stimulated BV2 microglia cells were treated with TAP2 (10 µM), the mRNA levels of proinflammatory mediators, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS), were markedly decreased by 54–83% as determined by quantitative PCR (qPCR) analysis. Furthermore, when TAP2 (25 nmol in 20 µL PBS) was intrathecally administered to the spinal nerve ligation-induced rats on day 3 after surgery, the mechanical allodynia was markedly decreased for approximately 2 weeks in von Frey filament tests, with a reduction in microglial activation. On immunohistochemical and qPCR analyses, both the level of reactive oxygen species and the gene expression of the proinflammatory mediators, such as TNF-α, IL-1β, IL-6, COX-2, and iNOS, were significantly decreased in the ipsilateral spinal dorsal horn. Finally, the analgesic effect of TAP2 was reproduced in rats with monoiodoacetate-induced osteoarthritic pain. The findings of the present study suggest that TAP2 efficiently mitigates neuropathic pain behavior by suppressing microglial activation, followed by downregulation of neuropathic pain-related factors, such as reactive oxygen species and proinflammatory molecules. Therefore, it may be useful as a new analgesic for treatment of neuropathic pain.


Subject(s)
Analgesics , Animals , Down-Regulation , Gene Expression , Hyperalgesia , Interleukin-6 , Interleukins , Ligation , Microglia , Neuralgia , Nitric Oxide Synthase Type II , Polymerase Chain Reaction , Prostaglandin-Endoperoxide Synthases , Rats , Reactive Oxygen Species , RNA, Messenger , Spinal Cord Dorsal Horn , Spinal Nerves , Toll-Like Receptor 4 , Toll-Like Receptors , Tumor Necrosis Factor-alpha
13.
Article in English | WPRIM | ID: wpr-763622

ABSTRACT

BACKGROUND: Increased oxidative stress and inflammation play a critical role in the etiopathogenesis of chronic tendinopathy. Melatonin is an endogenous molecule that exhibits antioxidant and anti-inflammatory activity. The aim of this study was to evaluate the biochemical and histopathological effects of exogenous melatonin administrations in supraspinatus overuse tendinopathy. METHODS: Fifty rats were divided into the following four groups: cage activity, melatonin treatment, corticosteriod therapy, and control. Melatonin (10 mg/kg, intraperitoneal; twice a day) and triamcinolone (0.3 mg/kg, subacromial; weekly) were administered to the treatment groups after the overuse period. Biochemical and histopathological evaluations were performed on serum samples and biopsies obtained from rats. Plasma inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels were evaluated biochemically. RESULTS: The TAS, TOS, OSI, iNOS, and VEGF values were significantly lower than the pre-treatment levels in rats receiving exogenous melatonin treatment (3 or 6 weeks) (p<0.05). TOS, iNOS, VEGF, and OSI values after 3 weeks of triamcinolone administration, and TOS, VEGF, and OSI levels after 6 weeks of triamcinolone application, were significantly lower than the pre-treatment levels (p<0.05). CONCLUSIONS: Exogenous melatonin application in overuse tendinopathy reduces oxidative stress and inflammation. Melatonin might be an alternative potential molecule to corticosteroids in the treatment of chronic tendinopathy.


Subject(s)
Adrenal Cortex Hormones , Animals , Biopsy , Inflammation , Melatonin , Models, Animal , Nitric Oxide Synthase Type II , Oxidative Stress , Plasma , Rats , Rotator Cuff , Shoulder , Tendinopathy , Triamcinolone , Vascular Endothelial Growth Factor A
14.
Article in English | WPRIM | ID: wpr-763025

ABSTRACT

We attempted to examine anti-inflammatory and anti-oxidant effects of 4′-O-β-D-glucosyl-5-O-methylvisamminol (GOMV), the first epigenetic inhibitor of histone phosphorylation at Ser10. While GOMV did not affect the viability of murine macrophage RAW 264.7 cells, it significantly suppressed lipopolysaccharide (LPS)-induced generation of prostaglandin E₂ (PGE₂) and nitric oxide (NO) through transcriptional inhibition of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). GOMV also scavenged free radicals in vitro, increased NF-E2-related factor 2 (NRF2), and activated antioxidant response element (ARE), thereby resulting in the induction of phase II cytoprotective enzymes in human keratinocyte HaCaT cells. Finally, GOMV significantly protected HaCaT cells against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative intracellular damages. Together, our results illustrate that GOMV possesses anti-inflammatory and anti-oxidant activity.


Subject(s)
Antioxidant Response Elements , Antioxidants , Cyclooxygenase 2 , Epigenomics , Free Radicals , Histones , Humans , In Vitro Techniques , Keratinocytes , Macrophages , NF-E2-Related Factor 2 , Nitric Oxide , Nitric Oxide Synthase Type II , Phosphorylation
15.
Article in English | WPRIM | ID: wpr-765022

ABSTRACT

BACKGROUND: Multiple sclerosis (MS) is an immune-associated inflammatory disorder of the central nervous system and results in serious disability. Although many disease-modifying therapy drugs have been developed, these drugs have shown limited clinical efficacy and some adverse effects in previous studies, therefore, there has been reasonable need for less harmful and cost-effective therapeutics. Herein, we tested the anti-inflammatory effect of sulforaphane (SFN) in a mouse model of experimental autoimmune encephalomyelitis (EAE). METHODS: The EAE mice were randomly assigned into two experimental groups: the phosphate-buffered saline (PBS)-treated EAE group and SFN-treated EAE group. After EAE mice induction by auto-immunization against the myelin oligodendrocyte glycoprotein peptide, we evaluated EAE symptom scores and biochemical analyses such as infiltration of inflammatory cells and demyelination of the spinal cord. Furthermore, western blotting was performed using the spinal cords of EAE mice. RESULTS: In the behavioral study, the SFN-treated EAE mice showed favorable clinical scores compared with PBS-treated EAE mice at the 13th day (1.30 ± 0.15 vs. 1.90 ± 0.18; P = 0.043) and 14th day (1.80 ± 0.13 vs. 2.75 ± 0.17; P = 0.003). Additionally, the biochemical studies revealed that SFN treatment inhibited the inflammatory infiltration, demyelinating injury of the spinal cords, and the up-regulation of inducible nitric oxide synthase in the EAE mice. CONCLUSION: The SFN treatment showed anti-inflammatory and anti-oxidative effects in the EAE mice. Conclusively, this study suggests that SFN has neuroprotective effects via anti-inflammatory processing, so it could be a new therapeutic or nutritional supplement for MS.


Subject(s)
Animals , Blotting, Western , Central Nervous System , Demyelinating Diseases , Encephalomyelitis, Autoimmune, Experimental , Mice , Multiple Sclerosis , Myelin-Oligodendrocyte Glycoprotein , Neuromyelitis Optica , Neuroprotective Agents , Nitric Oxide Synthase Type II , Spinal Cord , Treatment Outcome , Up-Regulation
16.
Article in Korean | WPRIM | ID: wpr-766388

ABSTRACT

There have been no published studies concerning the anti-inflammatory effects of corn silk on colon cancer cells. Thus, this study was conducted to investigate the effect of corn silk extract containing high levels of maysin on inflammation and its mechanism of action in colon cancer cells. SW 480 human colon cancer cells were treated with 1 µg/mL of lipopolysaccharide (LPS) to induce inflammation, and next they were treated with different concentrations of corn silk extract (0, 5, 10 and 15 µg/mL). The concentrations of nitric oxide (NO) were determined. The mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor α (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6), were determined. Western blot analysis was performed to determine the protein expressions of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases, and the latter consists of extracellular signal-related kinase (ERK), c-jun NH2-terminal kinase (JNK) and p38 MAP kinase (p38). The concentration of NO and the mRNA expression of iNOS were significantly and dose-dependently decreased in the corn silk-treated groups (P<0.05). The mRNA expression of TNF-α, IL-1β and IL-6 were significantly increased in the LPS-treated group (P<0.05), but these expressions were significantly and dose-dependently decreased in the corn silk treated groups (P<0.05). The protein expressions of NF-κB (in a dose-dependent fashion), ERK (at 10 and 15 µg/mL), JNK (at 15 µg/mL) and p38 (at 10 and 15 µg/mL) were significantly decreased with corn silk treatments (P<0.05). In conclusion, corn silk extract containing high levels of maysin seems to inhibit the LPS-induced inflammatory responses in SW480 colon cancer cells via the NF-κB pathway.


Subject(s)
Blotting, Western , Colon , Colonic Neoplasms , Cyclooxygenase 2 , Cytokines , Gene Expression , Humans , Inflammation , Interleukin-1beta , Interleukin-6 , Mitogen-Activated Protein Kinases , Nitric Oxide , Nitric Oxide Synthase Type II , p38 Mitogen-Activated Protein Kinases , Phosphotransferases , RNA, Messenger , Saccharin , Silk , Tumor Necrosis Factor-alpha , Zea mays
17.
Article in English | WPRIM | ID: wpr-762139

ABSTRACT

PURPOSE: In our previous study, we demonstrated that both titrated extract of Centella asiatica (TECA) and astaxanthin (AST) have anti-inflammatory effects in a 5% phthalic anhydride (PA) mouse model of atopic dermatitis (AD). The increasing prevalence of AD demands new therapeutic approaches for treating the disease. We investigated the therapeutic efficacy of the ointment form of TECA, AST and a TECA + AST combination in a mouse model of AD to see whether a combination of the reduced doses of 2 compounds could have a synergistic effect. METHODS: An AD-like lesion was induced by the topical application of 5% PA to the dorsal ear and back skin of an Hos:HR-1 mouse. After AD induction, TECA (0.5%), AST (0.5%) and the TECA (0.25%) + AST (0.25%) combination ointment (20 μg/cm2) were spread on the dorsum of the ear or back skin 3 times a week for 4 weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for inducible nitric oxide synthase (iNOS), cyclocxygenase (COX)-2, and nuclear factor (NF)-κB activity. We also measured the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and immunoglobulin E (IgE) in the blood of AD mice by enzyme-linked immunosorbent assay (ELISA). RESULTS: PA-induced skin morphological changes and ear thickness were significantly reduced by TECA, AST and TECA + AST treatments, but these inhibiting effects were more pronounced in the TECA + AST treatment. TECA, AST and the TECA+AST reatments inhibited the expression of iNOS and COX-2; NF-κB activity; and the release of TNF-α, IL-6 and IgE. However, the TECA+AST treatment showed additive or synergistic effects on AD. CONCLUSIONS: Our results demonstrate that the combination of TECA and AST could be a promising therapeutic agent for AD by inhibiting NF-κB signaling.


Subject(s)
Animals , Blotting, Western , Centella , Dermatitis , Dermatitis, Atopic , Ear , Enzyme-Linked Immunosorbent Assay , Immunoglobulin E , Immunoglobulins , Inflammation , Interleukin-6 , Interleukins , Mice , Nitric Oxide Synthase Type II , Prevalence , Skin , Tumor Necrosis Factor-alpha
18.
Article in English | WPRIM | ID: wpr-761814

ABSTRACT

Macrophage-associated inflammation is crucial for the pathogenesis of diverse diseases including metabolic disorders. Rhodanthpyrone (Rho) is an active component of Gentiana rhodantha, which has been used in traditional Chinese medicine to treat inflammation. Although synthesis procedures of RhoA and RhoB were reported, the biological effects of the specific compounds have never been explored. In this study, the anti-inflammatory activity and mechanisms of action of RhoA and RhoB were studied in lipopolysaccharide (LPS)-stimulated macrophages. Pretreatment with RhoA and RhoB decreased inducible nitric oxide synthase and cyclooxygenase-2 expressions in RAW 264.7 cells and in thioglycollate-elicited mouse peritoneal macrophages. In addition, it downregulated transcript levels of several inflammatory genes in LPS-stimulated RAW 264.7 cells, including inflammatory cytokines/chemokines (Tnfa, Il6, and Ccl2) and inflammatory mediators (Nos2 and Ptgs2). Macrophage chemotaxis was also inhibited by treatment with the compounds. Mechanistic studies revealed that RhoA and RhoB suppressed the nuclear factor (NF)-κB pathway, but not the canonical mitogen activated protein kinase pathway, in LPS-stimulated condition. Moreover, the inhibitory effect of RhoA and RhoB on inflammatory gene expressions was attenuated by treatment with an NF-κB inhibitor. Our findings suggest that RhoA and RhoB play an anti-inflammatory role at least in part by suppressing the NF-κB pathway during macrophage-mediated inflammation.


Subject(s)
Animals , Chemotaxis , Cyclooxygenase 2 , Gene Expression , Gentiana , Inflammation , Interleukin-6 , Macrophages , Macrophages, Peritoneal , Medicine, Chinese Traditional , Mice , Nitric Oxide Synthase Type II , Protein Kinases
19.
Acta cir. bras ; 34(4): e201900402, 2019. tab, graf
Article in English | LILACS | ID: biblio-1001091

ABSTRACT

Abstract Purpose: To evaluate the effect of amniotic fluid in liver preservation in organ transplantation, and compare it with standard preservation solutions. Methods: The groups consisted of Group 1: Ringer Lactate (RL) group, Group 2: HTK group, Group 3: UW group, Group 4: AF group. The livers of rats from Group 1, 2, 3, and 4 were perfused and placed into falcon tubes containing RL, HTK, UW, and AF solutions at +4‎°C, respectively. The tubes were stored for 12 hours in the refrigerator at +4°C. Tissue samples were taken at the 6th and 12th hours for histopathological examinations of the perfused livers, and storage solutions for biochemical analyzes at 6th and 12th hours. Results: AF was shown to maintain organ viability by reducing the number of cells undergoing apoptosis. Histopathological changes such as sinusoidal dilatation, hydropic degeneration, and focal necrosis were found to be similar to the groups in which the standard organ preservation solutions were used. Additionally, the results of INOS, IL-10, and TNF-α,which were evaluated immunohistochemically, have been shown to be similar to the UW and HTK groups. Conclusions: AF provided conservation similar to UW and HTK in the 12-hour liver SCS process. The fact that apoptosis values are comparable to standard preservation solutions supports the success of AF in the cold storage of the liver.


Subject(s)
Animals , Male , Cryopreservation/methods , Organ Preservation Solutions/pharmacology , Amniotic Fluid , Liver/blood supply , Liver/pathology , Organ Preservation/methods , Potassium Chloride/pharmacology , Procaine/pharmacology , Reference Values , Time Factors , Tissue Survival , Immunohistochemistry , Reperfusion Injury/prevention & control , Random Allocation , Reproducibility of Results , Tumor Necrosis Factor-alpha/analysis , Interleukin-10/analysis , Rats, Wistar , In Situ Nick-End Labeling , Nitric Oxide Synthase Type II/analysis , Ringer's Solution/pharmacology , Glucose/pharmacology , Mannitol/pharmacology
20.
Article in English | WPRIM | ID: wpr-764302

ABSTRACT

BACKGROUND: Baicalein is a bioactive flavone that is originally extracted from the root of Scutellaria baicalensis Georgi. This plant has long served as Chinese herbal medicine in the management of multiple diseases including inflammatory bowel diseases. Although it has been revealed that baicalein inhibits experimental colitis in mice, the molecular mechanisms still remain largely unrecognized. METHODS: The experimental colitis was induced in mice by 3% dextran sulfate sodium (DSS) in drinking water. The mice were given baicalein (10 or 25 mg/kg) by gavage for 7 days before and after DSS administration. Expression of COX-2 and inducible nitric oxide synthase (iNOS) and molecules involved in NF-κB signaling, such as inhibitor of κBα (IκBα), pIκBα, p65, and phospho-p65 was examined by Western blot analysis in the tissue of the mouse colon. Activity of IκB kinase β (IKKβ) was assessed by measuring the relative amount of radioactive γ-phosphate of ATP transferred to the IκBα substrate protein. The expression and phosphorylation of STAT3 and its target gene cyclin D1 were also measured. RESULTS: Baicalein prominently mitigated the severity of DSS-induced colitis in mice. It inhibited the expression of COX-2 and iNOS. Moreover, baicalein attenuated activity and phosphorylation of IKKβ and subsequent degradation of IκBα. Baicalein suppressed the phosphorylation and nuclear translocation of p65, resulting in a reduced DNA binding activity of NF-κB. Baicalein also suppressed the phosphorylation of STAT3 and expression of cyclin D1. Baicalein exhibited the synergistic effect on inhibition of COX-2 induced by DSS with curcumin, an ingredient of turmeric. CONCLUSIONS: Protective effects of baicalein on DSS-induced colitis are associated with suppression of NF-κB and STAT3 signaling pathways, which may contribute to its cancer preventive effects on colon carcinogenesis.


Subject(s)
Adenosine Triphosphate , Animals , Asian Continental Ancestry Group , Blotting, Western , Carcinogenesis , Colitis , Colon , Curcuma , Curcumin , Cyclin D1 , Cyclooxygenase 2 , Dextran Sulfate , Dextrans , DNA , Drinking Water , Herbal Medicine , Humans , Inflammatory Bowel Diseases , Mice , Nitric Oxide Synthase Type II , Phosphorylation , Phosphotransferases , Plants , Scutellaria baicalensis
SELECTION OF CITATIONS
SEARCH DETAIL