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1.
Chinese journal of integrative medicine ; (12): 905-913, 2023.
Article in English | WPRIM | ID: wpr-1010302

ABSTRACT

OBJECTIVE@#To investigate the anti-oxidant and anti-inflammatory effects of ethanol extract of Polygala sibirica L. var megalopha Fr. (EEP) on RAW264.7 mouse macrophages.@*METHODS@#RAW264.7 cells were pretreated with 0-200 µg/mL EEP or vehicle for 2 h prior to exposure to 1 µg/mL lipopolysaccharide (LPS) for 24 h. Nitric oxide (NO) and prostaglandin (PGE2) production were determined by Griess reagent and enzyme-linked immunosorbent assay (ELISA), respectively. The mRNA levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor α (TNF-α), interleukin-1beta (IL-1β), and IL-6 were determined using reverse transcription polymerase chain reaction (RT-PCR). Western blot assay was used to determine the protein expressions of iNOS, COX-2, phosphorylation of extracellular regulated protein kinases (ERK1/2), c-Jun N-terminal kinase (JNK), inhibitory subunit of nuclear factor Kappa B alpha (Iκ B-α) and p38. Immunofluorescence was used to observe the nuclear expression of nuclear factor-κ B p65 (NF-κ B p65). Additionally, the anti-oxidant potential of EEP was evaluated by reactive oxygen species (ROS) production and the activities of catalase (CAT) and superoxide dismutase (SOD). The 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (OH), superoxide anion (O2-) radical and nitrite scavenging activity were also measured.@*RESULTS@#The total polyphenol and flavonoid contents of EEP were 23.50±2.16 mg gallic acid equivalent/100 g and 43.78±3.81 mg rutin equivalent/100 g. With EEP treatment (100 and 150 µg/mL), there was a notable decrease in NO and PGE2 production induced by LPS in RAW264.7 cells by downregulation of iNOS and COX-2 mRNA and protein expressions (P<0.01 or P<0.05). Furthermore, with EEP treatment (150 µg/mL), there was a decrease in the mRNA expression levels of TNF-α, IL-1β and IL-6, as well as in the phosphorylation of ERK, JNK and p38 mitogen-activated protein kinase (MAPK, P<0.01 or P<0.05), by blocking the nuclear translocation of NF-κ B p65 in LPS-stimulated cells. In addition, EEP (100 and 150 µg/mL) led to an increase in the anti-oxidant enzymes activity of SOD and CAT, with a concomitant decrease in ROS production (P<0.01 or P<0.05). EEP also indicated the DPPH, OH, O2- radical and nitrite scavenging activity.@*CONCLUSION@#EEP inhibited inflammatory responses in activated macrophages through blocking MAPK/NF-κ B pathway and protected against oxidative stress.


Subject(s)
Animals , Mice , Antioxidants/pharmacology , Lipopolysaccharides/pharmacology , Polygala , Transcription Factor RelA/metabolism , Tumor Necrosis Factor-alpha/metabolism , Ethanol/chemistry , Interleukin-6/metabolism , Anti-Inflammatory Agents/chemistry , Reactive Oxygen Species/metabolism , Cyclooxygenase 2/metabolism , Nitrites/metabolism , NF-kappa B/metabolism , Nitric Oxide/metabolism , Superoxide Dismutase/metabolism , RNA, Messenger , Nitric Oxide Synthase Type II/metabolism
2.
Chinese Journal of Hepatology ; (12): 70-76, 2023.
Article in Chinese | WPRIM | ID: wpr-970954

ABSTRACT

Objective: To investigate the changes of intestinal wall barrier function and its correlation with infection occurrence in patients with cirrhotic portal hypertension. Methods: 263 patients with cirrhotic portal hypertension were split into: the clinically evident portal hypertension (CEPH) combined with infection group (n = 74); CEPH group (n = 104); and Non-CEPH group (n = 85). Among them, 20 CEPH patients and 12 non-CEPH patients in non-infection status were subjected to sigmoidoscopy. Immunohistochemical staining was used to detect the expression of trigger receptor-1 (TREM-1), CD68, CD14, the inducible nitric oxide synthase molecule, and Escherichia coli (E.coli) in the medullary cells of the colon mucosa. An enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of soluble myeloid cell trigger receptor-1 (sTREM-1), soluble leukocyte differentiation antigen-14 subtype (sCD14-ST) and intestinal wall permeability index enteric fatty acid binding protein (I-FABP). Fisher's exact probability method, one-way ANOVA, Kruskal-Wallis-H test, Bonferroni method, and Spearman correlation analysis were used for statistical analysis. Results: The serum sTREM-1 and I-FABP levels were higher in CEPH patients than those of non-CEPH patients in the non-infectious state (P < 0.05), but the difference in blood sCD14-ST levels was not statistically significant (P > 0.05). Serum levels of sTREM-1, sCD14-ST, and I-FABP in infected patients were higher than those in patients without a concurrent infection (P < 0.05). Serum sCD14-ST levels were positively correlated with serum sTREM-1, C-reactive protein (CRP), and procalcitonin (PCT), and sTREM-1 levels were also positively correlated with CRP and PCT (r > 0.5, P < 0.001). The rates of CD68, inducible nitric oxide synthase, CD14-positive cells, and E.coli-positive glands were higher in the intestinal mucosa of the CEPH group than those of the control group (P < 0.05). Spearman's correlation analysis showed that the rate of E.coli-positive glands in CEPH patients was positively correlated with the expression of molecular markers CD68 and CD14 in the lamina propria macrophages. Conclusion: Patients with cirrhotic portal hypertension have increased intestinal permeability and inflammatory cells, accompanied by bacterial translocation. Serum sCD14-ST and sTREM-1 can be used as indicators to predict and evaluate the occurrence of infection in patients with cirrhotic portal hypertension.


Subject(s)
Humans , Nitric Oxide Synthase Type II , Lipopolysaccharide Receptors , Prospective Studies , Biomarkers , C-Reactive Protein/analysis , Liver Cirrhosis/complications , Hypertension, Portal
3.
J. coloproctol. (Rio J., Impr.) ; 42(3): 238-244, July-Sept. 2022. ilus, graf
Article in English | LILACS | ID: biblio-1421983

ABSTRACT

Ulcerative colitis (UC) affects the mucosa and submucosa of the large intestine. One of the mechanisms involved in its etiology is oxidative stress (OS), directly involved in the inflammatory process characteristic of UC. The Campsiandra laurifolia, known as acapurana, was described as possessing antioxidant properties. We used 24 male Wistar rats, divided into control (CO), control + acapurana (CO + A), colitis (CL), and colitis + acapurana (CL + A) groups. This study performed histological analysis, measuring anal sphincter pressure (ASP) and lipoperoxidation (LPO). The activity of the antioxidant enzyme superoxide dismutase (SOD) and glutathione (GSH) levels were evaluated. The expression of the nuclear factor kappa B (NFkB) and inducible nitric oxide synthase (iNOS) was analyzed by immunohistochemistry. The statistical analysis used was the one-way analysis of variance (ANOVA), followed by the Student-Newman-Keuls test; values were expressed as mean ± standard error, and the significance level was p < 0.05. In the animals of the CL group, we observed the destruction of the crypts and the presence of mucosal ulcers, edema, and submucosal inflammatory infiltrate, as well as increased damage to the intestinal mucosa, reduced ASP, increased LPO and SOD activity, reduced GSH levels, and increased expression of NFkB and iNOS. The administration of C. laurifolia in the CL + A group was shown to cause regeneration of crypts, reduction of inflammatory infiltrate, reduction of damage to the intestinal mucosa, increase in ASP, and reduction in LPO with the restoration of SOD activity and GSH levels. The immunohistochemistry of NFkB and iNOS was significantly reduced. Therefore, the C. laurifolia aqueous extract appears to exert an antioxidant and anti-inflammatory effect in rats with AA-induced colitis. (AU)


Subject(s)
Animals , Rats , Colitis, Ulcerative/etiology , Fabaceae , Antioxidants , NF-kappa B , Nitric Oxide Synthase Type II , Intestinal Mucosa/anatomy & histology , Lipid Peroxides
4.
São Paulo; s.n; s.n; 2022. 141 p. graf, tab.
Thesis in Portuguese | LILACS | ID: biblio-1379329

ABSTRACT

Vários estudos epidemiológicos estabelecem correlação positiva entre os níveis de ácido úrico sérico e o aumento do risco para doenças cardiovasculares. Fatores dietéticos e socioeconômicos, além da presença de comorbidades estão diretamente associados aos níveis séricos de ácido úrico. Países desenvolvidos apresentam maior incidência e prevalência da gota e alguns grupos étnicos são particularmente susceptíveis à hiperuricemia. Cristais de ácido úrico são descritos por iniciar e perpetuar resposta inflamatória, e sinalizar um padrão de resposta molecular associado ao dano (DAMP), permitindo a diferenciação de macrófagos para perfis pró-inflamatórios. Por outro lado, os efeitos do ácido úrico em sua forma solúvel ainda carecem de estudos. Macrófagos derivados de precursores monocíticos apresentam diferenciação específica e respondem a um conjunto de fatores extrínsecos, resultando em perfis distintos, um fenômeno conhecido como polarização. Assim, os macrófagos podem ser classicamente ativados para uma resposta Th1 (T helper 1) e polarizados a um perfil pró- inflamatório (M1, resposta Th1) ou a um perfil alternativo e oposto, um perfil de resolução da inflamação (M2, resposta Th2, T helper 2). Nesse sentindo, buscamos analisar os efeitos do ácido úrico solúvel sobre vias de modulação da polarização fenotípica de macrófagos e modificação redox. Utilizamos a linhagem monocítica humana THP-1, a qual foi diferenciada em macrófagossímile por acetato miristato de forbol (PMA; 5 ng.mL-1) por 48 h, seguidas da incubação com ácido úrico em meio ausente de tióis e soro fetal bovino por 8h ou 24h (0-1000 µM). A expressão de fatores de transcrição e marcadores de polarização foi realizada através de citometria de fluxo, western-blotting e por microscopia de fluorescência com alto conteúdo de imagens (HCI). Em concentrações fisiológicas, verificamos que o ácido úrico solúvel regulou positivamente a frequência de células para receptor manose CD206, um marcador clássico de perfil alternativo/M2 e regulou negativamente a expressão óxido nítrico sintase induzível (iNOS), um marcador M1, sugerindo inicialmente uma modulação para o perfil de polarização M2. Além disso, as proteínas redoxsensíveis, heme oxigenase-1 (HO-1) e tiorredoxina (Trx) tiveram sua expressão reduzida e aumentada, respectivamente, pelo tratamento com ácido úrico. Os fatores de transcrição Nrf2 e STAT3 tiveram regulação negativa após a exposição ao ácido úrico solúvel. Os resultados apresentados nesta tese sugerem uma função do urato no priming de macrófagos através da alteração da polarização destas células


Several epidemiological studies have established a positive correlation between high serum uric acid levels and increased risk for cardiovascular diseases. Developed countries have a higher incidence and prevalence of gout and some ethnic groups are particularly susceptible to hyperuricemia. Although hyperuricemia is a prevalent condition, it has still controversy biological consequences. Uric acid crystals are described as capable of initiating and perpetuating inflammatory responses, by activating the damage-associated molecular response pattern (DAMP) cascade, allowing macrophage differentiation to inflammatory profiles. In spite of that, biological response to soluble uric acid are not completely understood. Monocyte-derived macrophages respond to a set of extrinsic factors that result in different profiles and can be polarized to a proinflammatory (M1) or anti-inflammatory (M2) profile. In this thesis, we analyzed the effects of soluble uric acid on redox-modulated pathways and the phenotypic polarization of macrophages. We used human monocytic THP-1 cell line, differentiated into macrophage by phorbol myristate acetate (PMA; 5 ng.mL-1) for 48 h. After differentiation, cells were incubated with soluble uric acid in medium without thiols and fetal bovine serum for 8 h and 24 h (0-1000 µM). The expression of transcription factors and polarization markers were assessed by flow cytometry, western-blotting and fluorescence microscopy with high content imaging (HCI). At physiological concentrations, soluble uric acid positively regulated the frequency of cells for mannose receptor CD206, a classic marker of the anti-inflammatory M2 profile and negatively regulated the inducible nitric oxide synthase (iNOS) expression, a proinflammatory M1 marker, suggesting that the soluble uric acid changes the polarization profile to M2 profile. In addition, the redox-sensitive proteins heme oxygenase-1 (HO-1) and thioredoxin (Trx) had their expression decreased and increased, respectively, after exposure to urate. STAT3 and Nrf2 transcription factors were downregulated upon soluble uric acid exposure. The results presented in this thesis suggest a role of uric acid in macrophage priming through the alteration of cell polarization


Subject(s)
Uric Acid/analysis , THP-1 Cells/classification , THP-1 Cells/chemistry , Inflammation/classification , Macrophages/chemistry , Sulfhydryl Compounds/agonists , Cardiovascular Diseases , Epidemiologic Studies , Nitric Oxide Synthase Type II/antagonists & inhibitors , Flow Cytometry/methods , Microscopy, Fluorescence/methods
5.
Acta cir. bras ; 36(10): e361006, 2021. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1349869

ABSTRACT

ABSTRACT Purpose: The rat cervicitis model was established with 20% phenol glue to explore the therapeutic effect of Kangfuxiaomi shuan II on rat cervicitis and its mechanism. Methods: After modeling, the rats were treated with Shuangzuotai suppository (37.84 mg/kg), Kangfuxiaoyan shuan (205.6 mg/kg) and Kangfuxiaomi shuan II (40, 80, 160 mg/kg). The histopathological changes and injury degree of cervix in rats were evaluated by vulvar inflammation score and organ index. The therapeutic effect of Kangfuxiaomi shuan II on cervicitis was evaluated by detecting the levels of copper-protein (CP), C-reactive protein (CRP), Rat interleukin 6 (IL-6), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and epidermal growth factor (EGF), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in cervical tissue. Results: Compared with the model group, the vulvar inflammation score and cervical index of rats in other groups decreased significantly (P<0.01). Kangfuxiaomi shuan II could significantly reduce the levels of CP, CRP, and MDA in serum of rats with cervicitis, and significantly increase the activity of SOD in serum of rats with cervicitis (P<0.01). The levels of EGF and iNOS in cervical tissue of rats also increased in different degrees, while the level of COX-2 decreased significantly (P<0.01), which significantly improved the pathological degree of vulvar inflammation in rats with cervicitis. Conclusions: Kangfuxiaomi shuan II has a certain therapeutic effect on cervicitis in rats, and its mechanism may be related to the regulation of inflammatory cytokine network and immunity.


Subject(s)
Animals , Female , Rats , Uterine Cervicitis/drug therapy , Superoxide Dismutase/metabolism , Cyclooxygenase 2/metabolism , Nitric Oxide Synthase Type II/metabolism , Malondialdehyde
6.
Biomedical and Environmental Sciences ; (12): 29-39, 2021.
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 , Male , Rats , Antimony/toxicity , Astrocytes/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Glial Fibrillary Acidic Protein/metabolism , MAP Kinase Kinase Kinases , Mice, Inbred ICR , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/metabolism , Signal Transduction/drug effects
7.
China Journal of Chinese Materia Medica ; (24): 3452-3458, 2020.
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)
Humans , Anti-Inflammatory Agents , Therapeutic Uses , Dendrobium , Inflammation , Drug Therapy , Lipopolysaccharides , Macrophages , NF-kappa B , Nitric Oxide , Nitric Oxide Synthase Type II
8.
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
9.
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
10.
Journal of Cancer Prevention ; : 129-138, 2019.
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)
Animals , Humans , Mice , Adenosine Triphosphate , Asian People , Blotting, Western , Carcinogenesis , Colitis , Colon , Curcuma , Curcumin , Cyclin D1 , Cyclooxygenase 2 , Dextran Sulfate , Dextrans , DNA , Drinking Water , Herbal Medicine , Inflammatory Bowel Diseases , Nitric Oxide Synthase Type II , Phosphorylation , Phosphotransferases , Plants , Scutellaria baicalensis
11.
International Journal of Oral Biology ; : 55-61, 2019.
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)
Animals , Rats , Alveolar Bone Loss , 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 , Silk , Tooth
12.
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 , Rats , 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 , RNA, Messenger , Rodentia , Sciatic Nerve , Spinal Cord , Spinal Cord Dorsal Horn
13.
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)
Animals , Rats , Analgesics , Down-Regulation , Gene Expression , Hyperalgesia , Interleukin-6 , Interleukins , Ligation , Microglia , Neuralgia , Nitric Oxide Synthase Type II , Polymerase Chain Reaction , Prostaglandin-Endoperoxide Synthases , Reactive Oxygen Species , RNA, Messenger , Spinal Cord Dorsal Horn , Spinal Nerves , Toll-Like Receptor 4 , Toll-Like Receptors , Tumor Necrosis Factor-alpha
14.
Journal of the Korean Shoulder and Elbow Society ; : 79-86, 2019.
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)
Animals , Rats , Adrenal Cortex Hormones , Biopsy , Inflammation , Melatonin , Models, Animal , Nitric Oxide Synthase Type II , Oxidative Stress , Plasma , Rotator Cuff , Shoulder , Tendinopathy , Triamcinolone , Vascular Endothelial Growth Factor A
15.
Biomolecules & Therapeutics ; : 381-385, 2019.
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)
Humans , Antioxidant Response Elements , Antioxidants , Cyclooxygenase 2 , Epigenomics , Free Radicals , Histones , In Vitro Techniques , Keratinocytes , Macrophages , NF-E2-Related Factor 2 , Nitric Oxide , Nitric Oxide Synthase Type II , Phosphorylation
16.
Journal of the Korean Dietetic Association ; : 217-228, 2019.
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)
Humans , Blotting, Western , Colon , Colonic Neoplasms , Cyclooxygenase 2 , Cytokines , Gene Expression , 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.
Journal of Korean Medical Science ; : e197-2019.
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 , Mice , Blotting, Western , Central Nervous System , Demyelinating Diseases , Encephalomyelitis, Autoimmune, Experimental , Multiple Sclerosis , Myelin-Oligodendrocyte Glycoprotein , Neuromyelitis Optica , Neuroprotective Agents , Nitric Oxide Synthase Type II , Spinal Cord , Treatment Outcome , Up-Regulation
18.
Nutrition Research and Practice ; : 279-285, 2019.
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 , Asia, Eastern , 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
19.
Nutrition Research and Practice ; : 189-195, 2019.
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 , Mice , Cyclooxygenase 2 , Cytokines , Cytosol , Dermatitis , Dermatitis, Contact , Dinoprostone , Ear , Edema , Garlic , In Vitro Techniques , Inhibitory Concentration 50 , Interleukin-6 , Macrophages , Necrosis , Neuroprotection , NF-kappa B , Nitric Oxide Synthase Type II
20.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 27-32, 2019.
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 , Mice , Anti-Inflammatory Agents , Chemistry , Pharmacology , Drugs, Chinese Herbal , Chemistry , Enzyme Inhibitors , Chemistry , Pharmacology , Ethanol , Chemistry , Flowers , Chemistry , Lonicera , Chemistry , Macrophages , Metabolism , Molecular Structure , Nitric Oxide , Metabolism , Nitric Oxide Synthase Type II , Plant Extracts , Chemistry , Plants, Edible , Chemistry , Triterpenes , Chemistry , Pharmacology
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