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1.
J Environ Pathol Toxicol Oncol ; 38(3): 229-238, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679310

RESUMO

Asthma has affected more than 300 million people worldwide and is considered one of the most debilitating global public health problems based on a recent statistical report from the Global Initiative for Asthma. Inflammation of the airways leads to the various interrelated mechanisms of innate and adaptive immunity acting mutually with the epithelium of the respiratory organ. Fucoxanthin is an orange or brown pigment which is naturally found in various seaweeds. To the best of our knowledge, there are no scientific claims or evidence of the curative effects of fucoxanthin against asthma. Hence, this present research was designed to investigate the curative activity of fucoxanthin against ovalbumin-induced asthma in a mouse model. Fucoxanthin (50 mg/kg) showed significant (P < 0.001) antiasthma activity. It effectively decreased intracellular secretion of reactive oxygen species and increased antioxidant enzyme activity. Fucoxanthin also decreased inflammatory cytokine markers in bronchoalveolar lavage fluid. Because fucoxanthin showed effective antiasthma activity against ovalbumin-induced asthma in experimental animals, further research on this natural antioxidant could lead to development of a novel drug for the treatment of asthma in humans.


Assuntos
Antiasmáticos/farmacologia , Antioxidantes/metabolismo , Asma/tratamento farmacológico , Citocinas/imunologia , Inflamação/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Xantofilas/farmacologia , Animais , Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar/química , Citocinas/efeitos dos fármacos , Inflamação/induzido quimicamente , Masculino , Camundongos , Ovalbumina/toxicidade
2.
J Environ Pathol Toxicol Oncol ; 38(3): 239-251, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679311

RESUMO

Fucoxanthin, a potent carotenoid present in various natural sources especially from seaweeds; it exhibits several biological effects like anti-neoplastic, anti-mutagenic, anti-diabetic, anti-obesity and anti-inflammatory actions. Fucoxanthin role in chemoprevention of lung cancer in mouse model induced using benzo(a)pyrene [B(a)P] has been presented here. Oral administration of fucoxanthin with and without B(a)P were studied, the results from our study shows that fucoxanthin significantly decreased tumor progression in mice exposed to B(a)P, the obtained data were correlated with increased antioxidant, apoptosis and decreased tumour marker and anti-apoptotic molecules. With respect to apoptosis, fucoxanthin treated animals shows increased apoptosis compared to tumor induced mice by increased expression of caspase 9 and 3 and decreased expression of anti-apoptotic Bcl2 protein. Finally, histopathological and immuno histochemical analysis also revealed that fucoxanthin shows potent anticancer agent by bringing back the damaged tissue treated with B(a)P and also decreases the expression of PCNA in cancer induced mice. The anticancer effect of fucoxanthin may be attributed by several independent mechanisms which play a important roles in the prevention of cancer development, there is also substantial evidences to show that fucoxanthin acts indirectly by increasing the antioxidant capacity of affected tissue and prepared to cope up with oxidative stress which is proved in our study. Thus from our study it is clearly established that fucoxanthin act as a persuasive anticancer drug against lung cancer.


Assuntos
Anti-Inflamatórios/farmacologia , Apoptose/imunologia , Inflamação/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Transdução de Sinais/imunologia , Xantofilas/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Benzo(a)pireno/toxicidade , Inflamação/induzido quimicamente , Masculino , Camundongos , Transdução de Sinais/efeitos dos fármacos
3.
J Environ Pathol Toxicol Oncol ; 38(3): 285-295, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679314

RESUMO

Psoriasis is an autoregulated immune and inflammation-based skin disease affecting approximately 3-4% of the worldwide population. Pinitol, conservatively used in ayurvedic medicine, has been shown to disclose an antiinflammatory effect, hold back the T-helper cells, and postpone cardiovascular diseases. In the present study we aimed to reveal the effect of D-pinitol on imiquimod (IMQ)-induced psoriasis-like skin inflammation in a mouse model via the nuclear factor-κB (NF-κB) pathway genes. In the current study, we found that D-pinitol ameliorated the skin abrasion and abridged epithelial thickness, inflammation numbers, and collagen-occupied regions in IMQ-induced psoriasis-like mice. The same results (epithelial thickness, inflammation numbers, and collagen-occupied regions) we achieved in dorsal skin regions. In addition, D-pinitol modified the lipid profile and antioxidant enzyme levels, which means that the IMQ-induced group showed elevated malondialdehyde when compared to D-pinitol. Downregulated expression of glutathione, superoxide dismutase, and catalase in the IMQ-induced group was incomparable with D-pinitol, control, and standard group. Additionally, inflammatory and NF-kB pathway gene levels in the psoriatic mouse skin, which includes tumor necrosis factor-α, interleukin [IL]-6, IL-17A, IL-23,TRAF3, NIK, IKKα, and RelB, were dramatically increased or decreased by treatment with D-pinitol. Histological and morphometric studies disclose the efficiency of D-pinitol. Finally, we found that D-pinitol reserved the TRAF3, NIK, IKKα, and RelB in the psoriatic skin, signifying that it restrains the commencement of NF-κB signaling pathways. The present results suggest that D-pinitol could prove to have tremendous preventive potential against the treatment and prevention of inflammatory disease.


Assuntos
Anti-Inflamatórios/farmacologia , Imiquimode/imunologia , Inflamação/tratamento farmacológico , Inositol/análogos & derivados , Psoríase/tratamento farmacológico , Animais , Inflamação/induzido quimicamente , Inflamação/imunologia , Inositol/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/imunologia , Psoríase/imunologia
4.
Life Sci ; 236: 116833, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31491456

RESUMO

AIMS: Inflammatory bowel disease is a chronic relapsing inflammation that affects the gastrointestinal tract, causing changes in colonic motility. The evolution of these changes is not completely understood and possibly related to symptoms that appear in different degrees of the intestinal inflammation. Therefore, our aim is evaluate during 14 days of assessment aspects of colonic contractility using 2,4,6-trinitrobenzenesulfonic acid (TNBS) model of inflammation in rats and associate the inflammatory process with colonic motility. METHODS: Contractility and inflammatory parameters were assessed in the same animal in six different moments: before intestinal inflammation induction, 2, 5, 8, 11, and 14 days after induction. The mechanical activity was determined by alternating current biosusceptometry (ACB) and subdivided into rhythmic propagating ripples (RPR) and rhythmic propulsive motor complexes (RPMC). We assessed inflammation by determining myeloperoxidase activity in feces. RESULTS: Transient and permanent changes were observed in colonic motility as a function of the inflammatory process evaluated through myeloperoxidase activity. We identified two contraction profiles: RPR and RPMC. The microscopic analysis demonstrated a depth of damage caused by an injury that was associated with changes in motility. CONCLUSIONS: We implemented a robust and adequate (specific) signal processing to quantify two measured colonic frequency patterns. Thus, we performed a detailed temporal analysis of the consequences of TNBS-induced inflammation on colonic motility in rats. Our approach enables further long-term assessments in the same animal with different mechanisms and duration of injury, remission, treatments and their motor consequences.


Assuntos
Colite/patologia , Modelos Animais de Doenças , Inflamação/patologia , Doenças Inflamatórias Intestinais/fisiopatologia , Mucosa Intestinal/fisiopatologia , Contração Muscular , Ácido Trinitrobenzenossulfônico/toxicidade , Animais , Colite/induzido quimicamente , Inflamação/induzido quimicamente , Masculino , Ratos , Ratos Wistar
5.
Life Sci ; 236: 116867, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31520598

RESUMO

AIM: Cyclophosphamide (CP) is a potent anticancer and immunosuppressant drug. Studies have shown significant oxidative stress and cognitive impairment but neuroinflammatory and histological aberrations with its administration is underexplored. Nerolidol (NER) is a lipophilic bioactive molecule with antioxidant and anti-inflammatory properties but it has not been explored for neuroprotective potential in CP-induced neurotoxic manifestations. Therefore, in the present study, we aimed to evaluate the neuroprotective potential of NER in CP-induced neuroinflammation and associated comorbid conditions like depression and cognitive dysfunctions. MATERIALS AND METHOD: In-silico study using Schrödinger software was used to assess the binding affinity of NER with Nrf2. In the In vivo study, NER 200 and 400 mg/kg p.o. were given from 1st day to 14th day. CP 200 mg/kg, i.p., was administered on the 7th day. After 24 h of the last dosing, neurobehavioral tests like spontaneous body alternation, passive avoidance and forced swim test were performed. On completion of study, mice were sacrificed, hippocampus and cortex were removed for biochemical estimations, histopathology and immunohistochemistry of p65 NF- κB and Nrf2. KEY FINDINGS: In-silico study showed significant binding of NER into the pocket domain of Nrf2. In-vivo study showed protective effect of NER against CP-induced neuroinflammation, oxidative stress, cognitive impairment and structural abnormalities in the hippocampus and cortex regions. SIGNIFICANCE: Findings of the study suggested that NER is a potential therapeutic molecule which can mitigate CP-induced neurotoxic manifestations via Nrf2 and NF-κB pathway. However, more detailed studies are needed to explicate the mechanism underlying its neuroprotective effect.


Assuntos
Disfunção Cognitiva/prevenção & controle , Ciclofosfamida/toxicidade , Inflamação/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Síndromes Neurotóxicas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Regulação da Expressão Gênica , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Imunossupressores/toxicidade , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/genética , Fármacos Neuroprotetores , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Transdução de Sinais
6.
Chemosphere ; 235: 1134-1145, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31561304

RESUMO

Particulate matter (PM) from layer house has adverse effect on people and chicken respiratory health, which can further influence animal performance and reduce production efficiency. However, little study focus on the respiratory inflammation induced by PM2.5 from layer house and the underlying mechanism also unclear. In this study, human adenocarcinoma alveolar basal epithelial cells (A549 cell) was subjected to the PM2.5 from layer house to evaluate the inflammation reaction caused by PM2.5 and explore the role of Nrf2 and autophagy in regulating the inflammation. Results showed that the viability of A549 cell decreased in a time - and concentration - dependent manner after PM2.5 treatment. TNFα, IL6, and IL8 increased significantly treated with PM2.5 at 12 h. RNA sequencing indicated differentially expressed genes were enriched in immune system process, oxidative stress (OS), endoplasmic reticulum stress (ERS), and autophagy. Further studies showed TLR4 - NFκB p65 signal pathway involved in the inflammation reaction caused by PM2.5. The overexpression of Nrf2 decreased the level of TNFα, IL6, IL8 markedly as well as the level of NFκB p65 and NFκB pp65. OS and ERS were also limited under overactivation of Nrf2 in PM2.5 treated cells. Autophagy induced by PM2.5 promoted the inflammation through increasing the level of NFκB p65 and NFκB pp65. Autophagy deficient strengthened the expression of Nrf2. Collectively, our study revealed Nrf2 prevents inflammation caused by layer house PM2.5 stimulation, however, autophagy exerts a promotive role in TLR4 - NFκB p65 mediating inflammation in A549 cell.


Assuntos
Autofagia/fisiologia , Inflamação/etiologia , Fator 2 Relacionado a NF-E2/fisiologia , Material Particulado/efeitos adversos , Receptor 4 Toll-Like/metabolismo , Fator de Transcrição RelA/metabolismo , Células A549 , Animais , Autofagia/efeitos dos fármacos , Estresse do Retículo Endoplasmático/genética , Humanos , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Fator 2 Relacionado a NF-E2/farmacologia , Estresse Oxidativo/genética , Transdução de Sinais
7.
Pestic Biochem Physiol ; 159: 68-79, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400786

RESUMO

Chlorpyrifos is a pesticide frequently detected in food and has been reported to disturb endocrine and gut health, which was regulated by gut microbiota and enteroendocrine cells. In this study, newly weaned (3 week) and adult (8 week) male rats fed a normal- or high- fat diet were chronically exposed to 0.3 mg chlorpyrifos/kg bodyweight/day. The effects of chlorpyrifos exposure on serum hormone levels, proinflammatory cytokines and gut microbiota were evaluated. Chronic exposure to chlorpyrifos significantly decreased the concentrations of luteinizing hormone, follicule stimulating hormone and testosterone, which was found only in the normal-fat diet. The counteracted effect of high-fat diet was also found in gut hormones and proinflammatory cytokines. Significantly higher concentrations of glucagon-like peptide-1, pancreatic polypeptide, peptide tyrosine tyrosine (PYY), ghrelin, gastric inhibitory poly-peptide, IL-6, monocyte chemoattractant protein-1, and TNF-α were found in rats exposed to chlorpyrifos beginning at newly weaned, whereas only the PYY, ghrelin and IL-6 concentrations increased significantly in rats exposed in adulthood. Furthermore, a decrease in epinephrine induced by chlorpyrifos exposure was found in rats exposed to chlorpyrifos beginning at newly weaned, regardless of their diet. Chlorpyrifos-induced disturbances in the microbiome community structure were more apparent in rats fed a high-fat diet and exposed beginning at newly weaned. The affected bacteria included short-chain fatty acid-producing bacteria (Romboutsia, Turicibacter, Clostridium sensu stricto 1, norank_f_Coriobacteriaceae, Faecalibaculum, Parasutterella and norank_f__Erysipelotrichaceae), testosterone-related genus (Turicibacter, Brevibacterium), pathogenic bacteria (Streptococcus), and inflammation-related bacteria (unclassified_f__Ruminococcaceae, Ruminococcaceae_UCG-009, Parasutterella, Oscillibacter), which regulated the endocrine system via the hypothalamic-pituitary-adrenal axis, as well as the immune response and gut barrier. Early exposure accelerated the endocrine-disturbing effect and immune responses of chlorpyrifos, although these effects can be eased or recovered by a high-fat diet. This study helped clarify the relationship between disrupted endocrine function and gut microbiota dysbiosis induced by food contaminants such as pesticides.


Assuntos
Clorpirifos/toxicidade , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/induzido quimicamente , RNA Ribossômico 16S/metabolismo , Envelhecimento , Animais , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Inflamação/metabolismo , Masculino , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Ratos
8.
Life Sci ; 233: 116731, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31394128

RESUMO

AIMS: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by widespread inflammation. LncRNA taurine-up-regulated gene 1 (TUG1) has been reported to be involved in multiple biological processes and human diseases. The aim of this study was to investigate the role of lncRNA TUG1 in MS and the underlying mechanism. MAIN METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in mice by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55). Lentiviral vectors encoding sh-TUG1 was constructed to silence TUG1 in MOG-EAE mice by intracerebroventricular (ICV) injection. The effect of TUG1 on inflammation in MS was evaluated by real-time PCR, Western blot, ELISA and Hematoxylin-eosin staining. To further study the mechanism of TUG1 in MS, TUG1 knockdown and miR-9-5p overexpression were performed in LPS-induced BV2 cells. KEY FINDINGS: Down-regulation of TUG1 improved mice behavior, reduced granulocyte-macrophage colony stimulating factor (GM-CSF) level, decreased the levels of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-6 and IL-17, and increased IL-10 in EAE mice. Notably, TUG1 expression was negatively correlated with miR-9-5p expression, while positively correlated with NF-κB1/p50. Knockdown of TUG1 or enforced expression of miR-9-5p inhibited LPS-induced inflammation in BV2 cells, while these effects were abolished by inhibition of miR-9-5p. We further verified that TUG1 negatively regulated miR-9-5p expression and NF-κB1/p50 is a direct target of miR-9-5p. SIGNIFICANCE: Down-regulation of TUG1 attenuates MS through inhibition of inflammation by sponging miR-9-5p via targeting NF-κB1/p50, suggesting that TUG1 is a potential therapeutic target for MS treatment.


Assuntos
Encefalomielite Autoimune Experimental/prevenção & controle , Regulação da Expressão Gênica , Inflamação/prevenção & controle , MicroRNAs/genética , Esclerose Múltipla/prevenção & controle , Subunidade p50 de NF-kappa B/metabolismo , RNA Longo não Codificante/antagonistas & inibidores , Animais , Apoptose , Proliferação de Células , Citocinas/metabolismo , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/patologia , Inflamação/induzido quimicamente , Inflamação/patologia , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Subunidade p50 de NF-kappa B/genética , RNA Longo não Codificante/genética , Ativação Transcricional
9.
Chem Biol Interact ; 310: 108743, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31299241

RESUMO

Paraquat (PQ) is a widely characterized neurotoxicant able to induce a series of nervous system disorders, including neurobehavioral defects and neurodegenerative diseases. Despite the direct evidence that PQ could induce inflammatory responses in central nervous system and largely contribute to neurotoxicity, the putative adverse effects of PQ on the neuroimmune interactions have rarely been investigated. Therefore, the present study investigated underlying mechanisms of PQ-induced inflammatory response in BV-2 microglia cells. Proliferation, migration and phagocytosis of BV-2 cells upon PQ exposure were first investigated to demonstrate that PQ did stimulate BV-2 microglia into an active phenotype. Increased microglia M1 markers expression and decreased microglia M2 markers expression confirmed that PQ induces BV-2 cells towards M1 activation. The levels of pro-inflammatory cytokines were determined using ELISA and western blotting assays, showing that paraquat significantly promote the secretion of pro-inflammatory mediators such as tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6). The up-regulation of TLR4/MyD88 protein expressions and enhanced translocation of NF-κB p65 protein upon PQ exposure were further demonstrated. Taken together, our results suggested that PQ induces M1 microglia polarization by increased production of pro-inflammatory molecules, which could be explained by the activation of the TLR4-mediated NF-κB signaling pathway.


Assuntos
Inflamação/induzido quimicamente , Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Paraquat/farmacologia , Animais , Citocinas/metabolismo , Camundongos , Microglia/patologia , NF-kappa B/efeitos dos fármacos , Paraquat/efeitos adversos , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Fator de Transcrição RelA/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo
10.
Life Sci ; 233: 116703, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31356903

RESUMO

AIMS: The initiation of pressure ulcers is accompanied by inflammation. Sinomenine emerges as a potential anti-inflammation agent. The aim of this study was to corroborate its anti-inflammatory property in skin keratinocyte HaCaT cells. Long non-coding RNA colon cancer associated transcript-1 (CCAT1)-associated mechanisms were also investigated. MAIN METHODS: HaCaT cells were stimulated with lipopolysaccharide (LPS) for 6 h after sinomenine pre-administration. Transfection was carried out to induce CCAT1 overexpression or silence it in HaCaT cells. Viability and apoptosis of HaCaT cells were determined by MMT and observed using flow cytometry, respectively. Protein expression was quantified using Western blot or ELISA. CCAT1 was measured by qRT-PCR. KEY FINDINGS: LPS notably decreased cell viability and exaggerated apoptosis with the cleavage of caspase-3/-9. The secretion of inflammatory factors was promoted. Sinomenine pre-administration maintained cell viability, blocked apoptosis and relieved inflammation with the decrease in cleaved caspase-3/-9 and inflammatory factors. LPS-induced phosphorylation of p65, IκBα and p38MAPK and overexpression of CCAT1 were precluded by sinomenine. CCAT1 overexpression, which per se induced inflammatory lesions, negated the positive effects of sinomenine with the restored phosphorylation of p65, IκBα, and p38MAPK. SIGNIFICANCE: Sinomenine played a protective role against LPS-induced inflammation. The anti-inflammatory activity of sinomenine might be mediated by CCAT1 down-regulation.


Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Queratinócitos/efeitos dos fármacos , Lipopolissacarídeos/efeitos adversos , Morfinanos/farmacologia , RNA Longo não Codificante/genética , Pele/efeitos dos fármacos , Antirreumáticos/farmacologia , Células Cultivadas , Regulação para Baixo , Regulação da Expressão Gênica , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Queratinócitos/citologia , Queratinócitos/metabolismo , Pele/citologia , Pele/metabolismo
11.
Environ Pollut ; 253: 667-679, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31330358

RESUMO

Many cities fail to meet air quality standards, which results in increased risk for pulmonary disorders, including asthma. Human and experimental studies have shown that diesel exhaust (DE) particles are associated with worsening of allergic asthma. Biodiesel (BD), a cleaner fuel from renewable sources, was introduced in the eighties. Because of the reduction in particulate matter (PM) emissions, BD was expected to cause fewer adverse pulmonary effects. However, only limited data on the effect of BD emissions in asthma are available. OBJECTIVE: Determine whether BD exhaust exposure in allergic sensitized mice leads to different effects on inflammatory and functional responses compared to DE exposure. METHODS: Balb/C mice were orotracheally sensitized with House Dust Mite (HDM) or a saline solution with 3 weekly instillations. From day 9 until day 17 after sensitization, they were exposed daily to filtered air (FA), DE and BD exhaust (concentration: 600 µg/m3 PM2.5). Lung function, bronchoalveolar lavage fluid (BALF) cell counts, cytokine levels (IL-2, IL-4, IL-5, IL-17, TNF-α, TSLP) in the BALF, peribronchiolar eosinophils and parenchymal macrophages were measured. RESULTS: HDM-sensitized animals presented increased lung elastance (p = 0.046), IgG1 serum levels (p = 0.029), peribronchiolar eosinophils (p = 0.028), BALF levels of total cells (p = 0.020), eosinophils (p = 0.028), IL-5 levels (p = 0.002) and TSLP levels (p = 0.046) in BALF. DE exposure alone increased lung elastance (p = 0.000) and BALF IL-4 levels (p = 0.045), whereas BD exposure alone increased BALF TSLP levels (p = 0.004). BD exposure did not influence any parameters after HDM challenge, while DE exposed animals presented increased BALF levels of total cells (p = 0.019), lymphocytes (p = 0.000), neutrophils (p = 0.040), macrophages (p = 0.034), BALF IL-4 levels (p = 0.028), and macrophagic inflammation in the lung tissue (p = 0.037), as well as decreased IgG1 (p = 0.046) and IgG2 (p = 0.043) levels when compared to the HDM group. CONCLUSION: The results indicate more adverse pulmonary effects of DE compared to BD exposure in allergic sensitized animals.


Assuntos
Biocombustíveis/toxicidade , Emissões de Veículos/toxicidade , Alérgenos , Animais , Asma/induzido quimicamente , Biocombustíveis/análise , Líquido da Lavagem Broncoalveolar , Citocinas , Modelos Animais de Doenças , Humanos , Inflamação/induzido quimicamente , Interleucina-17 , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos , Material Particulado/efeitos adversos , Testes de Toxicidade , Emissões de Veículos/análise
12.
Phytochemistry ; 164: 228-235, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31181354

RESUMO

Terminthia paniculata (Sanyeqi) is widely used for treating inflammation and rheumatic arthritis in the folk areas of Yunnan province, China. Its total extract was first revealed with xanthine oxidase (XO) inhibitory activity in vitro and anti-hyperuricemic effect in vivo. Bioassay-guided separation on Fr. A5 yielded six chalcone-flavonone heterodimers, termipaniculatones A-F. Their structures were elucidated based on extensive spectroscopic analyses involving HRESIMS, 1D and 2D NMR, UV, IR and [α]D, and the absolute configuration of termipaniculatone F was verified by ECD calculation. Termipaniculatones A and E showed obvious XO inhibitory activity with IC50 values of 55.6 and 89.5 µM, respectively, which took effects via a mix-type mode. A molecular modeling study revealed that termipaniculatone A was well located into the active site of XO by interacting with Glu802, Arg880, Thr1010 and Val1011 residues. Termipaniculatone A showed anti-hyperuricemic effects by decreasing serum uric acid levels and inhibiting XO activity in both serum and liver on potassium oxonate (PO)-induced hyperuricemia mice, and anti-inflammatory activity through alleviating paw swelling on monosodium urate (MSU)-induced mice, at the concentration of 20 mg/kg. This is the first time to reveal the anti-hyperuricemic and anti-acute gouty arthritis potency of T. paniculata and the characteristic biflavonoids as active constituents, which provides valuable information for searching new XO inhibitors from natural sources.


Assuntos
Anacardiaceae/química , Anti-Inflamatórios não Esteroides/farmacologia , Artrite Gotosa/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Hiperuricemia/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Artrite Gotosa/induzido quimicamente , Artrite Gotosa/metabolismo , Chalcona/química , Chalcona/isolamento & purificação , Chalcona/farmacologia , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/tratamento farmacológico , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Flavanonas/química , Flavanonas/isolamento & purificação , Flavanonas/farmacologia , Hiperuricemia/induzido quimicamente , Hiperuricemia/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos , Estrutura Molecular , Ácido Oxônico/antagonistas & inibidores , Relação Estrutura-Atividade , Ácido Úrico/antagonistas & inibidores , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismo
13.
Carbohydr Polym ; 219: 269-279, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31151525

RESUMO

The protective mechanism of chitosan oligosaccharide (COS) against lipopolysaccharides (LPS) -induced inflammatory responses in IPEC-J2 and in mice with DSS dextran sulfate sodium (DSS) -induced colitis is reported. Upon exposure to LPS, the proliferation rate of IPEC-J2 cells markedly decreased, and epithelial cell integrity was compromised. However, COS pretreatment significantly reduced these changes. Low-concentration (200 µg/mL) COS up-regulated Toll-like receptor 4 (TLR4) and nuclear p65 expression, but inhibited LPS-induced expression of nuclear p65, IL-6, and IL-8. Addition of the TLR4 inhibitor reduced nuclear p65, IL-6, and IL-8 expression in IPEC-J2 cells exposed to COS or LPS alone, and a slight up-regulation in nuclear p65 was observed in COS and LPS co-treated cells. Medium-dose COS (600 mg/kg/d) protected against DSS-induced colitis, in which TLR4 and nuclear p65 expression levels were decreased. We postulate that the prevention of both LPS- and DSS -induced inflammatory responses in IPEC-J2 cells and mice by COS are related to the inhibition of the TLR4/NF-κB signaling pathway.


Assuntos
Quitosana/farmacologia , Colite/tratamento farmacológico , Inflamação/tratamento farmacológico , Oligossacarídeos/farmacologia , Receptor 4 Toll-Like/metabolismo , Fator de Transcrição RelA/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Colite/induzido quimicamente , Sulfato de Dextrana/química , Modelos Animais de Doenças , Inflamação/induzido quimicamente , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lipopolissacarídeos/química , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos
14.
Food Chem Toxicol ; 131: 110583, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31220533

RESUMO

We investigated the anti-inflammatory activity of protopine (PTP) and sought to determine its mechanism of action in LPS-stimulated BV2 cells and a carrageenan (CA)-induced mouse model. Treatment with PTP (5, 10, and 20 µM) significantly suppresses the secretion of NO and PGE2 in a concentration-dependent manner without affecting cell viability by downregulating iNOS and COX-2 expression in LPS-induced BV2 cells. PTP also attenuates the production of pro-inflammatory chemokines, such as MCP-1, and cytokines, including TNF-α, IL-1ß and IL-6, and augments the expression of the anti-inflammatory cytokine IL-10. In addition, PTP suppresses the nuclear translocation of NF-κB by hindering the degradation of IκB and downregulating the expression of mitogen-activated protein kinases (MAPKs), including p38, ERK1/2 and JNK protein. Furthermore, PTP treatment significantly suppresses CA-induced paw oedema in mice compared to that seen in untreated mice. Expression of iNOS and COX-2 proteins is also abrogated by PTP (50 mg/kg) treatment in CA-induced mice. PTP treatment also abolishes IκB phosphorylation, which hinders the activation of NF-κB. Collectively, these results suggest PTP has potential for attenuating CA- and LPS-induced inflammatory symptoms through modulation of MAPKs/NF-κB signaling cascades.


Assuntos
Anti-Inflamatórios/uso terapêutico , Benzofenantridinas/uso terapêutico , Alcaloides de Berberina/uso terapêutico , Inflamação/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Animais , Anti-Inflamatórios/toxicidade , Benzofenantridinas/toxicidade , Alcaloides de Berberina/toxicidade , Carragenina , Linhagem Celular Transformada , Quimiocinas/metabolismo , Inflamação/induzido quimicamente , Lipopolissacarídeos , Camundongos Endogâmicos ICR , Proteínas Quinases Ativadas por Mitógeno/química , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Subunidade p50 de NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos
15.
Food Chem Toxicol ; 131: 110594, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31226431

RESUMO

The phytochemical composition and the antioxidant and anti-inflammatory activities of a mixture of 23 plants, named Horchata, traditionally consumed in Ecuador, have been evaluated. The study was carried out using the hydroalcoholic extract (HHext) and infusion (IHext) of the horchata plant mixture. It was verified that thermal treatment affected the contents of vitamin C and carotenoids, but hardly those of polyphenols, which would be the main bioactive compounds in the infusion, the common form of preparation of horchata for consumption. Among phenolic compounds, caffeoylquinic acids, flavones and flavonols (mostly quercetin glycosides) were prominent. Both HHext and IHext extracts managed to protect RAW 264.7 macrophages against LPS-induced cytotoxic damage, increasing the levels of endogenous antioxidant enzymes and modulating the production of pro-inflammatory and anti-inflammatory cytokines. Greater protective effects were obtained for HHext compared to IHext, which was in agreement with its higher content of phenolic compounds favoured by a more efficient extraction in the hydroalcoholic medium. Nonetheless, the infusion still maintained a significant antioxidant and anti-inflammatory activity, which would support the protective effects on health traditionally attributed to its consumption by the population.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Ácido Ascórbico/análise , Biomarcadores/metabolismo , Carotenoides/análise , Equador , Inflamação/induzido quimicamente , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos , Camundongos , Nitritos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plantas Medicinais/química , Polifenóis/análise , Células RAW 264.7 , Temperatura Ambiente , Fator de Necrose Tumoral alfa/metabolismo
16.
Biochimie ; 163: 152-162, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31199942

RESUMO

Extra-cellular signal regulated kinase-5 (Erk-5), a transcriptional activator and regulator of endothelial cells (ECs) homeostasis, has been implicated in shear stress-induced endothelial dysfunction (ED), however its role in oxidized low-density lipoprotein (oxLDL)- induced ED during metabolic stress is not known. Herein, regulation and function of Erk-5 in oxLDL-induced EC death, inflammation and dysfunction has been investigated. Primary Human Umbilical Vein Endothelial Cells (pHUVECs) were stimulated with oxLDL. MTT and Trypan blue exclusion assays to assess cell viability, RT-qPCR and Western blotting assays to determine expression of endothelial and inflammatory markers and ED mediators at mRNA and protein levels, respectively were performed. Monocyte adhesion assay was performed to examine monocytes adherence to oxLDL-stimulated pHUVECs. The exposure of oxLDL induced a dose- and time-dependent decrease in pHUVECs viability, which concurred with decreased Erk-5 expression. Further, oxLDL (100 µg/ml) decreased the expression of endothelial markers eNOS and vWF, and increased the expression of ICAM-1, at both mRNA and protein levels. SiRNA-mediated silencing of Erk-5 or its inhibition showed that changes in eNOS, vWF and ICAM-1 expression could be mediated through Erk-5. Furthermore, oxLDL decreased the levels of Erk-5's upstream regulator MEK5 and downstream regulators Mef2c and KLF2, which were similar to their expressions in Erk-5 silenced cells. Fisetin, a phytochemical and bioflavonoid, could reduce the effect of oxLDL in ECs by upregulating the expression of endothelial markers including Erk-5, and downregulating the expression of inflammation markers. These results suggest that Erk-5 could be a critical regulator of oxLDL-induced EC death, inflammation and dysfunction via downregulation of Erk-5/Mef2c-KLF2 signaling pathway, which can be ameliorated by a bioflavonoid, fisetin.


Assuntos
Flavonoides/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Lipoproteínas LDL/toxicidade , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Monócitos/fisiologia , Transdução de Sinais , Aterosclerose/induzido quimicamente , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Células Cultivadas , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Inflamação/prevenção & controle , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Lipoproteínas LDL/farmacologia , Fatores de Transcrição MEF2/genética , Fatores de Transcrição MEF2/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Substâncias Protetoras/farmacologia
17.
Mar Drugs ; 17(6)2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151271

RESUMO

In our previous study, a synthetic compound, (+)-(R,E)-6a1, that incorporated the key structures of anti-inflammatory algal metabolites and the endogenous peroxisome proliferator-activated receptor γ (PPAR-γ) ligand 15-deoxy-∆12,14-prostaglandin J2 (15d-PGJ2), exerted significant PPAR-γ transcriptional activity. Because PPAR-γ expressed in macrophages has been postulated as a negative regulator of inflammation, this study was designed to investigate the anti-inflammatory effect of the PPAR-γ agonist, (+)-(R,E)-6a1. Compound (+)-(R,E)-6a1 displayed in vitro anti-inflammatory activity in lipopolysaccharides (LPS)-stimulated murine RAW264.7 macrophages. Compound (+)-(R,E)-6a1 suppressed the expression of proinflammatory factors, such as nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), possibly by the inhibition of the nuclear factor-κB (NF-κB) pathway. In macrophages, (+)-(R,E)-6a1 suppressed LPS-induced phosphorylation of NF-κB, inhibitor of NF-κB α (IκBα), and IκB kinase (IKK). These results indicated that PPAR-γ agonist, (+)-(R,E)-6a1, exerts anti-inflammatory activity via inhibition of the NF-κB pathway.


Assuntos
Anti-Inflamatórios/farmacologia , Macrófagos/efeitos dos fármacos , NF-kappa B/agonistas , PPAR gama/antagonistas & inibidores , Prostaglandinas Sintéticas/farmacologia , Animais , Ciclo-Oxigenase 2/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/induzido quimicamente , Interleucina-6/genética , Lipopolissacarídeos , Camundongos , Óxido Nítrico/genética , Óxido Nítrico Sintase Tipo II/genética , Células RAW 264.7 , Rodófitas/química , Fator de Necrose Tumoral alfa/genética
18.
Environ Sci Pollut Res Int ; 26(18): 18200-18207, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31041709

RESUMO

Previous studies have shown that exposure to particulate matter (PM) increased variety of health problems, particularly cardiovascular diseases leading to premature mortality. The cardiac effects of particulate matter containing PM10 include increased infarct size, decreased heart function, and increased arrhythmias in experimental ischemia-reperfusion models in rats. The aim of this study was to evaluate the effects of particles with an aerodynamic diameter smaller than 10 µm (PM10) on isolated-rat heart and also to determine the efficacy of gallic acid (GA) as a preventive agent in oxidative damage. The healthy rats were divided into 8 equal groups which served as, control, GA, PM10 (0.5, 2.5, and 5 mg/kg), and PM10+GA groups. PM10 administered into the lungs via the trachea in two stages with 48-h interval. After all experiments, the electrocardiogram was recorded. Then, the hemodynamic parameters and ventricular arrhythmias in rat isolated-hearts were assessed using Langendorff apparatus and according to the Lambeth conventions. In addition, the inflammation and oxidative stress factors in cardiac tissues were evaluated in all groups. The obtained results showed that the exposure to PM caused to decrease in cardiac hemodynamic and electrocardiogram parameters. Also, in PM10 rat groups, the IL-6, TNF-α, and oxidative stress parameters were increased. Gallic acid preserved the value of cardiac parameters and inflammation in rat hearts. In summary, we added a novel therapeutic effect of gallic acid for cardiac dysfunction induced by particulate matter. These findings could be related to antioxidant and antiinflammation properties and the obtained results suggest that natural antioxidant like gallic acid could be a therapeutic agent in prevention and management of health issues in the polluted areas of the world.


Assuntos
Poluentes Atmosféricos/toxicidade , Ácido Gálico/farmacologia , Coração/efeitos dos fármacos , Material Particulado/toxicidade , Substâncias Protetoras/farmacologia , Animais , Arritmias Cardíacas/induzido quimicamente , Eletrocardiografia , Inflamação/induzido quimicamente , Inflamação/complicações , Masculino , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley
19.
Artif Cells Nanomed Biotechnol ; 47(1): 1808-1814, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31062615

RESUMO

BACKGROUND: Delayed inflammatory response is closely associated with the severity of Spinal cord injury (SCI). Herein, the function and molecular mechanism of notoginsenoside R1 (NGR1) in the in vitro model of SCI inflammation injury were explored. METHODS: PC-12 neuronal cells were subjected with LPS to construct a cell-based model of SCI inflammatory injury. NGR1 was applied in this cell model. miR-132 was silenced by transfection with miR-132 inhibitor. Cell viability and apoptosis were assessed, respectively. Then, the expression changes of pro-inflammatory cytokines and JNK pathway were examined. RESULTS: In this model, LPS was neurotoxic, with inhibiting PC-12 cell viability, inducing apoptosis, and enhancing concentrations of IL-6, IL-8 and TNF-α. However, NGR1 weakened the influence of LPS on PC-12 cells via elevating cell viability, decreasing apoptosis, decreasing pro-inflammatory cytokines expression, and suppressing activation of JNK signalling pathway. miR-132 was up-regulated by NGR1 treatment. Silence of miR-132 eliminated the influence of NGR1 on LPS-stimulated PC-12 cells. CONCLUSION: NGR1 relieved PC-12 cells from LPS-triggered inflammatory damage via elevating miR-132 and hereafter suppressing JNK pathway.


Assuntos
Ginsenosídeos/farmacologia , Lipopolissacarídeos/efeitos adversos , MicroRNAs/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/patologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , MicroRNAs/genética , Células PC12 , Ratos
20.
Analyst ; 144(11): 3546-3551, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31041945

RESUMO

A turn-on two-photon fluorescent probe HCA-Green for hypochlorous acid (HOCl) was synthesized using 4-methylamino-1,8-naphthalimide (MNA) as a two-photon fluorophore and p-hydroxyaniline as a leaving-recognition domain. Both the probe and the fluorophore were investigated under one- and two-photon excitation modes. The fluorescence intensity of the probe was enhanced by ∼229-fold and ∼193-fold under one-photon and two-photon excitation, respectively, after reacting with HOCl. A maximal two-photon action cross-section of 50 GM was obtained under excitation at 810 nm. The probe exhibited high sensitivity with a detection limit of 42.3 nM, as well as high selectivity, low cytotoxicity, and good photostability. Two-photon microscopy (TPM) was conducted to visualize HOCl levels in living cells and tissues. The production of endogenous HOCl induced by lipopolysaccharide-mediated inflammation was successfully monitored with this probe.


Assuntos
Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Inflamação/metabolismo , Animais , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Inflamação/induzido quimicamente , Luz , Limite de Detecção , Lipopolissacarídeos , Camundongos Nus , Microscopia de Fluorescência/métodos , Ratos
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