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1.
J Ethnopharmacol ; 333: 118496, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38936643

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: Schinus terebinthifolia Raddi (Anacardiaceae), known as Brazilian pepper tree, stands out as a medicinal plant widely used in traditional medicine. The leaves are popularly used as anti-inflammatory agent and to relieve inflammatory conditions such as bronchitis, ulcers, and wounds, for example. AIM OF THE STUDY: The present study evaluated the acute toxicity, genotoxicity, and anti-inflammatory activity of S. terebinthifolia leaf lectin (SteLL) in mice (Mus musculus). MATERIALS AND METHODS: In the acute toxicity assay, the animals were treated intraperitoneally (i.p.) or orally (per os) with a single dose of 100 mg/kg. Genotoxicity was assessed by the comet and micronucleus assays. Carrageenan-induced peritonitis and paw edema models were used to evaluate the anti-inflammatory effects of SteLL (1, 5 and 10 mg/kg, i.p.). RESULTS: No animal died and no signs of intoxication or histopathological damage were observed in the acute toxicity assay. Genotoxic effect was not detected. In peritonitis assay, SteLL reduced in 56-69% leukocyte migration to the peritoneal cavity; neutrophil count decreased by 25-32%, while mononuclear cell count increased by 67-74%. SteLL promoted a notable reduction of paw edema after 4 h (61.1-63.4%). Morphometric analysis showed that SteLL also decreased the thickness of epidermal edema (30.2-40.7%). Furthermore, SteLL decreased MPO activity, plasma leakage, NO release, and modulated cytokines in both peritoneal fluid and paw homogenate. CONCLUSION: SteLL did not induce acute toxicity or genotoxicity in mice and stands out as a promising candidate in the development of new phytopharmaceuticals with anti-inflammatory action.


Assuntos
Anacardiaceae , Anti-Inflamatórios , Edema , Extratos Vegetais , Folhas de Planta , Animais , Anacardiaceae/química , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Masculino , Edema/tratamento farmacológico , Edema/induzido quimicamente , Extratos Vegetais/farmacologia , Lectinas de Plantas/farmacologia , Lectinas de Plantas/isolamento & purificação , Testes de Toxicidade Aguda , Peritonite/tratamento farmacológico , Peritonite/induzido quimicamente , Testes para Micronúcleos , Feminino , Carragenina , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Schinus
2.
Cells ; 13(11)2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38891050

RESUMO

Acute inflammation is a rapid and dynamic process involving the recruitment and activation of multiple cell types in a coordinated and precise manner. Here, we investigate the origin and transcriptional reprogramming of monocytes using a model of acute inflammation, zymosan-induced peritonitis. Monocyte trafficking and adoptive transfer experiments confirmed that monocytes undergo rapid phenotypic change as they exit the blood and give rise to monocyte-derived macrophages that persist during the resolution of inflammation. Single-cell transcriptomics revealed significant heterogeneity within the surface marker-defined CD11b+Ly6G-Ly6Chi monocyte populations within the blood and at the site of inflammation. We show that two major transcriptional reprogramming events occur during the initial six hours of Ly6Chi monocyte mobilisation, one in the blood priming monocytes for migration and a second at the site of inflammation. Pathway analysis revealed an important role for oxidative phosphorylation (OxPhos) during both these reprogramming events. Experimentally, we demonstrate that OxPhos via the intact mitochondrial electron transport chain is essential for murine and human monocyte chemotaxis. Moreover, OxPhos is needed for monocyte-to-macrophage differentiation and macrophage M(IL-4) polarisation. These new findings from transcriptional profiling open up the possibility that shifting monocyte metabolic capacity towards OxPhos could facilitate enhanced macrophage M2-like polarisation to aid inflammation resolution and tissue repair.


Assuntos
Antígenos Ly , Diferenciação Celular , Inflamação , Macrófagos , Monócitos , Fosforilação Oxidativa , Monócitos/metabolismo , Animais , Macrófagos/metabolismo , Inflamação/patologia , Inflamação/metabolismo , Humanos , Camundongos , Antígenos Ly/metabolismo , Quimiotaxia , Camundongos Endogâmicos C57BL , Peritonite/metabolismo , Peritonite/induzido quimicamente , Peritonite/patologia , Zimosan/farmacologia , Mitocôndrias/metabolismo , Reprogramação Celular
3.
Biosci Biotechnol Biochem ; 88(8): 966-978, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-38772744

RESUMO

The NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome triggers the maturation of interleukin-1ß (IL-1ß) and is implicated in the pathogenesis of various inflammatory diseases. Urolithin A, a gut microbial metabolite of ellagic acid, reportedly exerts antiinflammatory effects in vitro and in vivo. However, whether urolithin A suppresses NLRP3 inflammasome activation is unclear. In this study, urolithin A inhibited the cleavage of NLRP3 inflammasome agonist-induced caspase-1, maturation of IL-1ß, and activation of pyroptosis in lipopolysaccharide-primed mouse bone marrow-derived macrophages. Urolithin A reduced generation of intracellular and mitochondrial reactive oxygen species (ROS) and restricted the interaction between thioredoxin-interacting protein and NLRP3, which attenuated NLRP3 inflammasome activation. Urolithin A administration prevented monosodium urate-induced peritonitis in mice. Collectively, these findings indicate that urolithin A suppresses NLRP3 inflammasome activation, at least partially, by repressing the generation of intracellular and mitochondrial ROS.


Assuntos
Cumarínicos , Inflamassomos , Interleucina-1beta , Proteína 3 que Contém Domínio de Pirina da Família NLR , Peritonite , Espécies Reativas de Oxigênio , Ácido Úrico , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Cumarínicos/farmacologia , Cumarínicos/química , Espécies Reativas de Oxigênio/metabolismo , Peritonite/tratamento farmacológico , Peritonite/metabolismo , Peritonite/induzido quimicamente , Ácido Úrico/metabolismo , Inflamassomos/metabolismo , Camundongos , Interleucina-1beta/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Caspase 1/metabolismo , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Lipopolissacarídeos , Piroptose/efeitos dos fármacos , Proteínas de Transporte , Tiorredoxinas
4.
Int Immunopharmacol ; 133: 112123, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38663314

RESUMO

The NOD-like receptor family protein 3 (NLRP3) inflammasome is a crucial complex for the host to establish inflammatory immune responses and plays vital roles in a series of disorders, including Alzheimer's disease and acute peritonitis. However, its regulatory mechanism remains largely unclear. Zinc finger antiviral protein (ZAP), also known as zinc finger CCCH-type antiviral protein 1 (ZC3HAV1), promotes viral RNA degradation and plays vital roles in host antiviral immune responses. However, the role of ZAP in inflammation, especially in NLRP3 activation, is unclear. Here, we show that ZAP interacts with NLRP3 and promotes NLRP3 oligomerization, thus facilitating NLRP3 inflammasome activation in peritoneal macrophages of C57BL/6 mice. The shorter isoform of ZAP (ZAPS) appears to play a greater role than the full-length isoform (ZAPL) in HEK293T cells. Congruously, Zap-deficient C57BL/6 mice may be less susceptible to alum-induced peritonitis and lipopolysaccharide-induced sepsis in vivo. Therefore, we propose that ZAP is a positive regulator of NLRP3 activation and a potential therapeutic target for NLRP3-related inflammatory disorders.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Peritonite , Animais , Humanos , Masculino , Camundongos , Células HEK293 , Inflamassomos/metabolismo , Inflamassomos/imunologia , Lipopolissacarídeos/imunologia , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Peritonite/imunologia , Peritonite/induzido quimicamente , Multimerização Proteica , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Sepse/imunologia , Sepse/metabolismo
5.
Molecules ; 29(8)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38675622

RESUMO

IRAK4 is a critical mediator in NF-κB-regulated inflammatory signaling and has emerged as a promising therapeutic target for the treatment of autoimmune diseases; however, none of its inhibitors have received FDA approval. In this study, we identified a novel small-molecule IRAK4 kinase inhibitor, DW18134, with an IC50 value of 11.2 nM. DW18134 dose-dependently inhibited the phosphorylation of IRAK4 and IKK in primary peritoneal macrophages and RAW264.7 cells, inhibiting the secretion of TNF-α and IL-6 in both cell lines. The in vivo study demonstrated the efficacy of DW18134, significantly attenuating behavioral scores in an LPS-induced peritonitis model. Mechanistically, DW18134 reduced serum TNF-α and IL-6 levels and attenuated inflammatory tissue injury. By directly blocking IRAK4 activation, DW18134 diminished liver macrophage infiltration and the expression of related inflammatory cytokines in peritonitis mice. Additionally, in the DSS-induced colitis model, DW18134 significantly reduced the disease activity index (DAI) and normalized food and water intake and body weight. Furthermore, DW18134 restored intestinal damage and reduced inflammatory cytokine expression in mice by blocking the IRAK4 signaling pathway. Notably, DW18134 protected DSS-threatened intestinal barrier function by upregulating tight junction gene expression. In conclusion, our findings reported a novel IRAK4 inhibitor, DW18134, as a promising candidate for treating inflammatory diseases, including peritonitis and IBD.


Assuntos
Doenças Inflamatórias Intestinais , Quinases Associadas a Receptores de Interleucina-1 , Peritonite , Animais , Quinases Associadas a Receptores de Interleucina-1/antagonistas & inibidores , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Camundongos , Peritonite/tratamento farmacológico , Peritonite/induzido quimicamente , Células RAW 264.7 , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Modelos Animais de Doenças , Transdução de Sinais/efeitos dos fármacos , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Humanos , Masculino , Fosforilação/efeitos dos fármacos , Citocinas/metabolismo , NF-kappa B/metabolismo , Camundongos Endogâmicos C57BL
6.
Int J Mol Sci ; 25(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38674081

RESUMO

Marrubiin is a diterpene with a long history of a wide range of biological activities. In this study, the anti-inflammatory effects of marrubiin were investigated using several in vitro and in vivo assays. Marrubiin inhibited carrageenan-induced peritoneal inflammation by preventing inflammatory cell infiltration and peritoneal mast cell degranulation. The anti-inflammatory activity was further demonstrated by monitoring a set of biochemical parameters, showing that the peritoneal fluid of animals treated with marrubiin had lower levels of proteins and lower myeloperoxidase activity compared with the fluid of animals that were not treated. Marrubiin exerted the most pronounced cytotoxic activity towards peripheral mononuclear cells, being the main contributors to peritoneal inflammation. Additionally, a moderate lipoxygenase inhibition activity of marrubiin was observed.


Assuntos
Anti-Inflamatórios , Carragenina , Diterpenos , Mastócitos , Animais , Carragenina/efeitos adversos , Camundongos , Diterpenos/farmacologia , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Anti-Inflamatórios/farmacologia , Camundongos Endogâmicos C57BL , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Peritonite/metabolismo , Peritonite/patologia , Masculino , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Inflamação/patologia , Degranulação Celular/efeitos dos fármacos , Peroxidase/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo
7.
Perit Dial Int ; 44(2): 145-148, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37743776

RESUMO

Vancomycin has been reported to cause vancomycin flushing reaction (VFR), a hypersensitivity reaction that mostly occurs after intravenous administration. The incidence of VFR in a patient receiving intraperitoneal vancomycin is rare. We report a case of a female peritoneal dialysis (PD) patient with a PD-related peritonitis who developed VFR after intraperitoneal administration of 2000 mg vancomycin. Seventy-five minutes after instillation, she developed flushing, a pruritic erythema on the upper body and swelling of the lips. Blood results revealed a vancomycin plasma concentration of 54.8 mg/L and a normal tryptase level. During a relapse of her PD-related peritonitis, vancomycin was successfully reintroduced in a 50% reduced dose. No symptoms of VFR developed, and the corresponding vancomycin plasma concentration was 33.6 mg/L. Intraperitoneal treatment was continued with 500 mg vancomycin every 2-3 days with frequently measured, adequate trough levels ranging from 15-22 mg/L. This case illustrates the risk factors for the development of VFR after intraperitoneal administration of vancomycin, namely a high and concentrated loading dose together with a low body weight, a fast peritoneal transport state and peritonitis. Reintroduction of vancomycin after occurrence of VFR is safe, but a lower loading dose or a slower instillation rate is recommended.


Assuntos
Diálise Peritoneal , Peritonite , Humanos , Feminino , Vancomicina/efeitos adversos , Diálise Peritoneal/efeitos adversos , Peritônio , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Injeções Intraperitoneais , Antibacterianos/efeitos adversos
8.
J Ethnopharmacol ; 322: 117561, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38072290

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Syringa Pubescens Turcz. (SP), a member of the Oleaceae family, is a species of plant known as Syringa. Flowers, as the medicinal part, are commonly used in the treatment of hepatitis and tonsillitis. AIM OF THE STUDY: The research was the first to assess the antioxidant and anti-inflammatory potential of different parts of SP flowers (SPF) in vitro. The most promising fraction was ethyl acetate fraction of SP flower (SPFEA). The antioxidant, anti-inflammatory and analgesic activities of SPFEA were further studied, and the chemical components were identified. METHODS: HPLC was used to identify the major components in various fraction of SPF. DPPH and ABTS + radical scavenging assays as well as FRAP test and ß-carotene bleaching test were employed to assess the antioxidant potential of SPF fraction in vitro. The inhibitory effect on NO production in LPS-treated RAW264.7 cells and heat-induced protein denaturation test were used to evaluate the anti-inflammatory potential of SPF fraction. Further analysis of the biological activity of SPFEA was performed. Acute toxicity test was conducted to assess the toxicity of SPFEA. The anti-inflammatory effect was assessed by utilizing xylene induced ear edema model, carrageenan-induced foot edema model and peritonitis model in vivo. The analgesic effect of SPFEA was evaluated using hot plate test, tail immersion test, formaldehyde test as well as acetic acid-induced abdominal writhing pain experiment in vivo. In carrageenan induced foot edema model, ELISA kits were employed to measure levels of inflammation factors (NO, TNF-α, IL-6, COX-2, IL-1ß) in foot tissue as well as MDA, CAT, SOD, GSH-PX levels in liver tissue. RESULTS: HPLC results showed that there were significant differences in bioactive substances among different fractions of SPF, and SPFEA was rich in bioacitve components. Compared with other fractions of SPF, SPFEA exhibited better antioxidant and anti-inflammatory abilities. The 3000 mg/kg SPFEA group in mice had no obvious side effects. The xylene-induced ear edema model, carrageenan-induced foot edema and peritonitis models demonstrated that the SPFEA had significant anti-inflammatory effect. Moreover, inflammation factors including NO, TNF-α, IL-6, COX-2, IL-1ß were significantly reduced in SPFEA groups in foot tissue induced by carrageenan. Additionally, SPFEA effectively decreased liver tissue oxidative stress levels (MDA, SOD, GSH-PX and CAT). The bioactivities of SPFEA demonstrated a clear dose-dependent relationship. The results of the hot plate test, tail immersion test, formaldehyde test and acetic acid-induced abdominal writhing pain experiments indicated the SPFEA possessed an excellent analgesic effect, and this effect was in dose-dependent manner. CONCLUSION: The study provides a scientific foundation for understanding the pharmacological action of SPFEA. It has been indicated that SPFEA has excellent antioxidant, analgesic and anti-inflammatory effects.


Assuntos
Acetatos , Peritonite , Syringa , Camundongos , Animais , Antioxidantes/efeitos adversos , Carragenina , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Fator de Necrose Tumoral alfa , Interleucina-6 , Ciclo-Oxigenase 2/metabolismo , Xilenos , Dor/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Ácido Acético/uso terapêutico , Formaldeído , Flores/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Superóxido Dismutase/metabolismo
9.
Nephrol Dial Transplant ; 39(2): 222-232, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-37429598

RESUMO

BACKGROUND: Peritoneal dialysis (PD) solutions containing low levels of glucose degradation products (GDPs) are associated with attenuation of peritoneal membrane injury and vascular complications. However, clinical benefits associated with neutral-pH, low-GDP (N-pH/L-GDP) solutions remain unclear. METHODS: Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the associations between N-pH/L-GDP solutions and all-cause mortality, cause-specific mortality, transfer to haemodialysis (HD) for ≥30 days and PD peritonitis in adult incident PD patients in Australia and New Zealand between 1 January 2005 and 31 December 2020 using adjusted Cox regression analyses. RESULTS: Of 12 814 incident PD patients, 2282 (18%) were on N-pH/L-GDP solutions. The proportion of patients on N-pH/L-GDP solutions each year increased from 11% in 2005 to 33% in 2017. During the study period, 5330 (42%) patients died, 4977 (39%) experienced transfer to HD and 5502 (43%) experienced PD peritonitis. Compared with the use of conventional solutions only, the use of any form of N-pH/L-GDP solution was associated with reduced risks of all-cause mortality {adjusted hazard ratio [aHR] 0.67 [95% confidence interval (CI) 0.61-0.74]}, cardiovascular mortality [aHR 0.65 (95% CI 0.56-0.77)], infection-related mortality [aHR 0.62 (95% CI 0.47-0.83)] and transfer to HD [aHR 0.79 (95% CI 0.72-0.86)] but an increased risk of PD peritonitis [aHR 1.16 (95% CI 1.07-1.26)]. CONCLUSIONS: Patients who received N-pH/L-GDP solutions had decreased risks of all-cause and cause-specific mortality despite an increased risk of PD peritonitis. Studies assessing the causal relationships are warranted to determine the clinical benefits of N-pH/L-GDP solutions.


Assuntos
Diálise Peritoneal , Peritonite , Adulto , Humanos , Diálise Renal/efeitos adversos , Diálise Peritoneal/efeitos adversos , Soluções para Diálise/efeitos adversos , Peritonite/etiologia , Peritonite/induzido quimicamente , Concentração de Íons de Hidrogênio
10.
Front Immunol ; 14: 1251026, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38094294

RESUMO

Introduction: The study explores the role of endothelial Semaphorin 7A (SEMA7A) in inflammatory processes. SEMA7A is known for enhancing inflammation during tissue hypoxia and exhibiting anti-inflammatory properties in the intestinal system during colitis. This research extends the understanding of SEMA7A's function by examining its role in inflammatory peritonitis and intestinal inflammation. Methods: The research involved inducing peritonitis in SEMA7A knockout (SEMA7A-/-) and wild-type (WT) animals through Zymosan A (ZyA) injection. The inflammatory response was assessed by measuring cell count and cytokine release. In parallel, the study investigated the expression of SEMA7A in intestinal epithelial cells under inflammatory stimuli and its impact on interleukin 10 (IL-10) production using an in vitro co-culture model of monocytes and epithelial cells. Additionally, the distribution of SEMA7A target receptors, particularly ITGAV/ITGB1 (CD51/CD29), was analyzed in WT animals. Results: The results revealed that SEMA7A-/- animals exhibited increased inflammatory peritonitis compared to the WT animals. Inflammatory conditions in intestinal epithelial cells led to the induction of SEMA7A. The co-culture experiments demonstrated that SEMA7A induced IL-10 production, which depended on integrin receptors and was independent of PLXNC1 expression. Furthermore, ITGAV/ITGB1 emerged as the predominant SEMA7A receptor in the intestinal area of WT animals. Discussion: These findings underscore the multifaceted role of SEMA7A in inflammatory processes. The differential responses in peritonitis and intestinal inflammation suggest that SEMA7A's function is significantly influenced by the expression and distribution of its target receptors within different organ systems. The study highlights the complex and context-dependent nature of SEMA7A in mediating inflammatory responses.


Assuntos
Peritonite , Semaforinas , Animais , Antígenos CD/metabolismo , Integrinas , Interleucina-10/genética , Semaforinas/genética , Semaforinas/metabolismo , Peritonite/induzido quimicamente , Inflamação
11.
CuidArte, Enferm ; 17(2): 197-203, jul.-dez. 2023. graf, ilus
Artigo em Português | BDENF | ID: biblio-1552910

RESUMO

Introdução: A Garcinia gardneriana é utilizada na medicina tradicional brasileira para o tratamento de tumores, inflamações e alívio de dores, mas as informações científicas são ainda limitadas. Objetivos: Diante do uso popular e o anseio por efeitos colaterais mínimos, o objetivo geral deste estudo foi avaliar as propriedades anti-inflamatórias da G. gardneriana em modelo de peritonite induzido por lipopolissacarideo (LPS). Métodos: Ratos Wistar foram divididos aleatoriamente em 3 grupos (n= 5/ grupo): controle, induzido à peritonite e não tratado e induzido à peritonite e tratado com extrato de folhas alcoólico de G. gardneriana a 4%. A peritonite foi induzida por única injeção intraperitoneal de LPS (1 mg/kg). O tratamento com o extrato foi realizado por gavagem (1 ml), administrado antes e 12h após a injeção do LPS. Os ratos foram eutanasiados após 24h da indução de peritonite. Amostras de sangue foram coletadas para análise plasmática de histamina, o lavado intraperitoneal para quantificação de neutrófilos e o intestino delgado para processamento histológico, quantificação de mastócitos e imuno-histoquímica da expressão da proteína Anexina A1 (AnxA1). Resultados: As análises quantitativas indicaram os efeitos anti-inflamatórios do extrato, pela redução do recrutamento de neutrófilos para a cavidade peritoneal e a diminuição da quantidade de mastócitos na lâmina própria do intestino delgado, comparadas aos animais não tratados. Não houve diferença estatística dos níveis de histamina. A imuno-histoquímica indicou diminuição acentuada da expressão da AnxA1 na mucosa intestinal dos animais tratados. Conclusão: Nossos dados demonstraram que o extrato alcoólico de G. gardneriana tem forte ação anti-inflamatória e potencial terapêutico para o desenvolvimento de fitoterápicos com propriedades anti-inflamatórias


Introduction: Garcinia gardneriana is used in traditional Brazilian medicine for the treatment of tumors, inflammation and relief of pain, but scientific information is still limited. Objective: In the face of popular use and the desire for minimal side effects, the general objective of this study was to evaluate the anti-inflammatory properties of G. gardneriana in a model of lipopolysaccharide-induced peritonitis (LPS). Methods: Wistar rats were randomly divided into 3 groups (n = 5 / group): control, induced to peritonitis and untreated and induced to peritonitis and treated with 4% alcoholic extract of G. gardneriana leaves. Peritonitis was induced by single intraperitoneal injection of LPS (1 mg/kg). Treatment with the extract was performed by gavage (1 ml), given before and 12h after LPS injection. The rats were euthanized 24h after the peritonitis induction. Blood samples were collected for plasma analysis of histamine, intraperitoneal lavage for quantification of neutrophils and the small intestine for histological processing for quantification of mast cells, and immunohistochemical analysis of the expression of Annexin A1 (AnxA1) protein. Results: Quantification analyses indicated the anti-inflammatory effects of the extract by reducing the recruitment of neutrophils into the peritoneal cavity and reducing the amount of mast cells in the lamina propria of the small intestine compared to the untreated animals. There was no statistical difference in the levels of histamine. Immunohistochemical studies indicated a marked decrease of the AnxA1 expression in the intestinal mucosa of the treated animals. Conclusion: Our data demonstrated that the alcoholic extract of G. gardneriana has a strong anti-inflammatory action and therapeutic potential for the development of herbal products with anti-inflammatory properties


Introducción: Garcinia gardneriana se utiliza en la medicina tradicional brasileña para el tratamiento de tumores, inflamaciones y alivio del dolor, pero la información científica aún es limitada. Objetivo: Frente al uso popular y la búsqueda de efectos secundarios mínimos, lo objetivo general de este estudio fue evaluar las propiedades antiinflamatorias de G. gardneriana en un modelo de peritonitis inducido por lipopolisacárido (LPS). Métodos: Se dividieron aleatoriamente ratas Wistar en 3 grupos (n= 5/grupo): control, inducido a peritonitis y no tratado, e inducido a peritonitis y tratado con extracto alcohólico de hojas de G. gardneriana al 4%. La peritonitis fue inducida por una única inyección intraperitoneal de LPS (1 mg/kg). El tratamiento con el extracto se realizó por gavaje (1 ml), administrado antes y 12 horas después de la inyección de LPS. Las ratas fueron sacrificadas después de 24 horas de la inducción de peritonitis. Se recopilaron muestras de sangre para el análisis plasmático de histamina, el lavado intraperitoneal para la cuantificación de neutrófilos y el intestino delgado para el procesamiento histológico, la cuantificación de mastocitos y la inmunohistoquímica de la expresión de la proteína Anexina A1 (AnxA1). Resultados: Los análisis cuantitativos indicaron los efectos antiinflamatorios del extracto, mediante la reducción del reclutamiento de neutrófilos en la cavidad peritoneal y la disminución de la cantidad de mastocitos en la lámina propia del intestino delgado, en comparación con los animales no tratados. No hubo diferencia estadística en los niveles de histamina. La inmunohistoquímica indicó una disminución pronunciada de la expresión de AnxA1 en la mucosa intestinal de los animales tratados. Conclusión: Nuestros datos demostraron que el extracto alcohólico de G. gardneriana tiene una fuerte acción antiinflamatoria y potencial terapéutico para el desarrollo de fitoterapéuticos con propiedades antiinflamatorias.


Assuntos
Animais , Feminino , Ratos , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Garcinia/química , Lipopolissacarídeos , Ratos Wistar
12.
Mar Drugs ; 21(11)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37999381

RESUMO

Fucans from marine algae have been the object of many studies that demonstrated a broad spectrum of biological activities, including anti-inflammatory effects. The aim of this study was to verify the protective effects of a fucan extracted from the brown algae Spatoglossum schröederi in animals submitted to a generalized inflammation model induced by zymosan (ZIGI). BALB/c mice were first submitted to zymosan-induced peritonitis to evaluate the treatment dose capable of inhibiting the induced cellular migration in a simple model of inflammation. Mice were treated by the intravenous route with three doses (20, 10, and 5 mg/kg) of our fucan and, 1 h later, were inoculated with an intraperitoneal dose of zymosan (40 mg/kg). Peritoneal exudate was collected 24 h later for the evaluation of leukocyte migration. Doses of the fucan of Spatoglossum schröederi at 20 and 10 mg/kg reduced peritoneal cellular migration and were selected to perform ZIGI experiments. In the ZIGI model, treatment was administered 1 h before and 6 h after the zymosan inoculation (500 mg/kg). Treatments and challenges were administered via intravenous and intraperitoneal routes, respectively. Systemic toxicity was assessed 6 h after inoculation, based on three clinical signs (bristly hair, prostration, and diarrhea). The peritoneal exudate was collected to assess cellular migration and IL-6 levels, while blood samples were collected to determine IL-6, ALT, and AST levels. Liver tissue was collected for histopathological analysis. In another experimental series, weight loss was evaluated for 15 days after zymosan inoculation and fucan treatment. The fucan treatment did not present any effect on ZIGI systemic toxicity; however, a fucan dose of 20 mg/kg was capable of reducing the weight loss in treated mice. The treatment with both doses also reduced the cellular migration and reduced IL-6 levels in peritoneal exudate and serum in doses of 20 and 10 mg/kg, respectively. They also presented a protective effect in the liver, with a reduction in hepatic transaminase levels in both doses of treatment and attenuated histological damage in the liver at a dose of 10 mg/kg. Fucan from S. schröederi presented a promising pharmacological activity upon the murine model of ZIGI, with potential anti-inflammatory and hepatic protective effects, and should be the target of profound and elucidative studies.


Assuntos
Peritonite , Phaeophyceae , Camundongos , Animais , Zimosan/toxicidade , Interleucina-6 , Modelos Animais de Doenças , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Ascite , Redução de Peso
13.
STAR Protoc ; 4(3): 102554, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37682717

RESUMO

Although intraperitoneal injection of monosodium urate (MSU) is an effective model for studying peritonitis, its establishment remains challenging. Here, we present a protocol for using MSU to activate the NLRP3 inflammasome in bone-marrow-derived macrophages (BMDMs) and to induce peritonitis in mice. We describe steps for isolating and culturing BMDMs, preparing MSU crystals, and activating the NLRP3 inflammasome using western blot and ELISA. We then detail procedures for inducing peritonitis and testing for relevant indicators using flow cytometry and ELISA. For complete details on the use and execution of this protocol, please refer to Huang et al. (2023).1.


Assuntos
Inflamassomos , Peritonite , Camundongos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ácido Úrico/farmacologia , Macrófagos , Peritonite/induzido quimicamente
14.
Inflamm Res ; 72(8): 1567-1581, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37438583

RESUMO

BACKGROUND: Intercellular communication between macrophages and peritoneal mesothelial cells (PMCs) has been suggested as a key factor regulating peritonitis development. Here, we explored whether PPARγ (peroxisome proliferator-activated receptor gamma) can be packaged into macrophage exosomes to mediate intercellular communication and regulate peritonitis. METHODS: Macrophage exosomes were isolated by ultracentrifugation and identified by nanoparticle tracking analysis and transmission electron microscopy. Proteomic analysis of macrophage-derived exosomes was performed using mass spectrometry. Co-culture models of supernatants or exosomes with PMCs, as well as a mouse peritonitis model induced by lipopolysaccharide (LPS), were employed. RESULTS:  In this study, using stable Raw264.7 cells overexpressing GFP-FLAG-PPARγ (OE-PPARγ), we found that PPARγ inhibited LPS-induced inflammatory responses in Raw264.7 cells and that PPARγ was incorporated into macrophage exosomes during this process. Overexpression of PPARγ mainly regulated the secretion of differentially expressed exosomal proteins involved in the biological processes of protein transport, lipid metabolic process, cell cycle, apoptotic process, DNA damage stimulus, as well as the KEGG pathway of salmonella infection. Using co-culture models and mouse peritonitis model, we showed that exosomes from Raw264.7 cells overexpressing PPARγ inhibited LPS-induced inflammation in co-cultured human PMCs and in mice through downregulating CD14 and TLR4, two key regulators of the salmonella infection pathway. Pretreatment of the PPARγ inhibitor GW9662 abolished the anti-inflammatory effect of exosomes from Raw264.7 OE-PPARγ cells on human PMCs. CONCLUSIONS: These results suggested that overexpression of PPARγ largely altered the proteomic profile of macrophage exosomes and that exosomal PPARγ from macrophages acted as a regulator of intercellular communication to suppress LPS-induced inflammatory responses in vitro and in vivo via negatively regulating the CD14/TLR4 axis.


Assuntos
Fenômenos Biológicos , Peritonite , Camundongos , Humanos , Animais , PPAR gama/metabolismo , Lipopolissacarídeos/farmacologia , Receptor 4 Toll-Like/metabolismo , Proteômica , Macrófagos/metabolismo , Peritonite/induzido quimicamente
15.
Cell Mol Life Sci ; 80(8): 230, 2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37498355

RESUMO

The aberrant activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is known to contribute to the pathogenesis of various human inflammation-related diseases. However, to date, no small-molecule NLRP3 inhibitor has been used in clinical settings. In this study, we have identified SB-222200 as a novel direct NLRP3 inhibitor through the use of drug affinity responsive target stability assay, cellular thermal shift assay, and surface plasmon resonance analysis. SB-222200 effectively inhibits the activation of the NLRP3 inflammasome in macrophages, while having no impact on the activation of NLRC4 or AIM2 inflammasome. Furthermore, SB-222200 directly binds to the NLRP3 protein, inhibiting NLRP3 inflammasome assembly by blocking the NEK7 - NLRP3 interaction and NLRP3 oligomerization. Importantly, treatment with SB-222200 demonstrates alleviation of NLRP3-dependent inflammatory diseases in mouse models, such as monosodium urate crystal-induced peritonitis and dextran sulfate sodium-induced acute intestinal inflammation. Therefore, SB-222200 holds promise as a lead compound for the development of NLRP3 inhibitors to combat NLRP3-driven disease and serves as a versatile tool for pharmacologically investigating NLRP3 biology.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Peritonite , Camundongos , Animais , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Peritonite/metabolismo , Macrófagos/metabolismo , Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Interleucina-1beta/metabolismo
16.
Food Funct ; 14(14): 6690-6706, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37403713

RESUMO

Our group has previously reported on the phytochemical composition and biological activities of a phenolic-enriched maple syrup extract (MSX), which showed promising anti-inflammatory effects in several disease models including diabetes and Alzheimer's disease. However, the efficacious doses of MSX and its molecular targets involved in the anti-inflammatory effects are not fully elucidated. Herein, the efficacy of MSX in a peritonitis mouse model was evaluated in a dose-finding study and the underlying mechanisms were explored using data-independent acquisition (DIA) proteomics assay. MSX (at 15, 30 and 60 mg kg-1) alleviated lipopolysaccharide-induced peritonitis by reducing the levels of pro-inflammatory cytokines including interleukin-1 beta (IL-1ß), IL-6, and tumor necrosis factor alpha (TNF-α) in the serum and major organs of the mice. Furthermore, DIA proteomics analyses identified a panel of proteins that were significantly altered (both up- and down-regulated) in the peritonitis group, which were counteracted by the MSX treatments. MSX treatment also modulated several inflammatory upstream regulators including interferon gamma and TNF. Ingenuity pathway analysis suggested that MSX may modulate several signaling pathways in the processes of initiation of cytokine storm, activation of liver regeneration, and suppression of hepatocyte apoptosis. Together, these proteomic and in vivo findings indicate that MSX could regulate inflammation signaling pathways and modulate inflammatory markers and proteins, providing critical insight to its therapeutic potential.


Assuntos
Acer , Peritonite , Camundongos , Animais , Acer/química , Lipopolissacarídeos/efeitos adversos , Extratos Vegetais/farmacologia , Proteômica , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Peritonite/metabolismo , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Fenóis/farmacologia
17.
Molecules ; 28(7)2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37049845

RESUMO

Oreochromis niloticus (tilapia) is one of the most cultivated fish species worldwide. Tilapia farming generates organic waste from fish removal processes in nurseries. Visceral waste can damage natural ecosystems. Therefore, the use of this material as a source of biomolecules helps reduce environmental impacts and improve pharmacological studies. Tilapia viscera were subjected to proteolysis and complexation with an ion-exchange resin. The obtained glycosaminoglycans were purified using ion exchange chromatography (DEAE-Sephacel). The electrophoretic profile and analysis of 1H/13C nuclear magnetic resonance (NMR) spectra allowed for the characterization of the compound as chondroitin sulfate and its sulfation position. This chondroitin was named CST. We tested the ability of CST to reduce leukocyte influx in acute peritonitis models induced by sodium thioglycolate and found a significant reduction in leukocyte migration to the peritoneal cavity, similar to the polymorphonuclear population of the three tested doses of CST. This study shows, for the first time, the potential of CST obtained from O. niloticus waste as an anti-inflammatory drug, thereby contributing to the expansion of the study of molecules with pharmacological functions.


Assuntos
Ciclídeos , Peritonite , Tilápia , Animais , Sulfatos de Condroitina , Ecossistema , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico
18.
Mar Drugs ; 21(4)2023 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-37103384

RESUMO

The aim of this study was to identify the chemical composition and sequential structure of alginate isolated from C. crinita harvested in the Bulgarian Black Sea, as well as its effects in histamine-induced paw inflammation in rats. The serum levels of TNF-α, IL-1ß, IL-6, and IL-10 in rats with systemic inflammation, and the levels of TNF-α in a model of acute peritonitis in rats were also investigated. The structural characterization of the polysaccharide was obtained by FTIR, SEC-MALS, and 1H NMR. The extracted alginate had an M/G ratio of 1.018, a molecular weight of 7.31 × 104 g/mol, and a polydispersity index of 1.38. C. crinita alginate in doses of 25 and 100 mg/kg showed well-defined anti-inflammatory activity in the model of paw edema. A significant decrease in serum levels of IL-1ß was observed only in animals treated with C. crinita alginate in a dose of 25 mg/kg bw. The concentrations of TNF-α and IL-6 in serum were significantly reduced in rats treated with both doses of the polysaccharide, but no statistical significance was observed in the levels of the anti-inflammatory cytokine IL-10. A single dose of alginate did not significantly alter the levels of the pro-inflammatory cytokine TNF-α in the peritoneal fluid of rats with a model of peritonitis.


Assuntos
Peritonite , Phaeophyceae , Ratos , Animais , Alginatos/efeitos adversos , Interleucina-10 , Fator de Necrose Tumoral alfa , Interleucina-6 , Mar Negro , Bulgária , Anti-Inflamatórios , Citocinas , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Polissacarídeos/química , Edema/tratamento farmacológico
19.
J Ethnopharmacol ; 309: 116353, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-36907476

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ageratum conyzoides L. (Asteraceae), a well-known and widely distributed traditional tropical medicinal herb, has been used to treat diverse diseases. Our preliminary research has shown that aqueous extracts of A. conyzoides leaf (EAC) have anti-inflammatory activity. However, the detailed underlying anti-inflammatory mechanism of EAC is still unclear. AIM OF THE STUDY: To determine the anti-inflammatory mechanism of action of EAC. MATERIALS AND METHODS: The major constituents of EAC were identified by ultra-performance liquid chromatography (UPLC) combined with quadrupole-time-of-flight mass/mass spectrometry (UPLC-Q-TOF-MS/MS). LPS and ATP were used to activate the NLRP3 inflammasome in two types of macrophages (RAW 264.7 and THP-1 cells). The cytotoxicity of EAC was measured by the CCK8 assay. The levels of inflammatory cytokines and NLRP3 inflammasome-related proteins were detected by ELISA and western blotting (WB), respectively. The oligomerization of NLRP3 and ASC and the resulting inflammasome complex formation were observed by immunofluorescence. The intracellular reactive oxygen species (ROS) level was measured by flow cytometry. Finally, an MSU-induced peritonitis model was established to evaluate the anti-inflammatory effects of EAC in vivo. RESULTS: Twenty constituents were identified in the EAC. Kaempferol 3,7-diglucoside, 1,3,5-tricaffeoylquinic acid, and kaempferol 3,7,4'-triglucoside were found to be the most potent ingredients. EAC significantly reduced the levels of IL-1ß, IL-18, TNF-α, and caspase-1 in the two types of activated macrophages, implying that EAC can inhibit the activation of the NLRP3 inflammasome. A mechanistic study revealed that EAC inhibited NLRP3 inflammasome activation by blocking NF-κB signalling pathway activation and scavenging the level of intracellular ROS to prevent NLRP3 inflammasome assembly in macrophages. Furthermore, EAC attenuated the in vivo expression of inflammatory cytokines by suppressing NLRP3 inflammasome activation in a peritonitis mouse model. CONCLUSION: Our results demonstrated that EAC inhibited inflammation by suppressing NLRP3 inflammasome activation, highlighting that this traditional herbal medicine might be used to treat NLRP3 inflammasome-driven inflammatory diseases.


Assuntos
Ageratum , Peritonite , Animais , Camundongos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Quempferóis/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Massas em Tandem , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Citocinas/metabolismo , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Interleucina-1beta/metabolismo
20.
Int J Mol Sci ; 24(6)2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36982834

RESUMO

Chronic kidney disease (CKD) incidence is growing worldwide, with a significant percentage of CKD patients reaching end-stage renal disease (ESRD) and requiring kidney replacement therapies (KRT). Peritoneal dialysis (PD) is a convenient KRT presenting benefices as home therapy. In PD patients, the peritoneum is chronically exposed to PD fluids containing supraphysiologic concentrations of glucose or other osmotic agents, leading to the activation of cellular and molecular processes of damage, including inflammation and fibrosis. Importantly, peritonitis episodes enhance peritoneum inflammation status and accelerate peritoneal injury. Here, we review the role of immune cells in the damage of the peritoneal membrane (PM) by repeated exposure to PD fluids during KRT as well as by bacterial or viral infections. We also discuss the anti-inflammatory properties of current clinical treatments of CKD patients in KRT and their potential effect on preserving PM integrity. Finally, given the current importance of coronavirus disease 2019 (COVID-19) disease, we also analyze here the implications of this disease in CKD and KRT.


Assuntos
COVID-19 , Falência Renal Crônica , Peritonite , Insuficiência Renal Crônica , Humanos , Peritônio , Diálise Renal/efeitos adversos , COVID-19/complicações , Soluções para Diálise/efeitos adversos , Peritonite/induzido quimicamente , Insuficiência Renal Crônica/complicações , Inflamação/complicações , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Imunidade
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