Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.481
Filtrar
1.
Food Res Int ; 149: 110703, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34600695

RESUMO

Chia (Salvia hispanica L.) is an herbaceous plant used as omega-3 polyunsaturated fatty acid (ω-3 PUFA) source that presents a range of beneficial effects on human health. Herein, it was used a chia oil containing over than 62% of α-linolenic acid (ALA), a compound widely related to anti-inflammatory actions. Chia oil effect was tested using paw edema and mechanical hyperalgesia induced by carrageenan, and ear edema induced by croton oil, histamine, and capsaicin. Croton oil was used in both preventive and therapeutic treatment schedules of chia oil while histamine and capsaicin were used only in preventive treatment schedule. Chia oil mechanism of action was investigated using nociception and paw edema response induced by intraplantar injection of acidified saline (ASIC activator), PGE2 (prostaglandin pathway), cinnamaldehyde (TRPA1 activator), bradykinin (BK pathway), menthol (TRPM8 activator), and capsaicin (TRPV1 activator). Further, RT-PCR for inflammatory mediators (TRPA1, NF-κB, PPAR-γ, COX-2, IL-6, TNF, FPR2, FAAH, MAGL, and IL-12A) induced by carrageenan, NLRP3 inflammasome activation, and the cell viability were then accessed. Later, chia oil actions were evaluated in the experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis (MS) model. Chia oil showed anti-edematogenic and anti-hyperalgesic effects when administered 1 h before pro-inflammatory stimulus - particularly carrageenan and croton oil. Moreover, chia oil upregulated the mRNA levels of COX-2 and formyl peptide receptor 2 (FPR2) while reduced IL-6 expression in the spinal cord of mice submitted to i.pl. injection of carrageenan. Interestingly, chia oil mediates antinociceptive effects in mice decreasing the nociceptive response induced by acidified saline, PGE2, and cinnamaldehyde, but not by bradykinin, menthol, and capsaicin. On the EAE model, chia oil preventively administered attenuated EAE-induced motor deficits and mechanical hyperalgesia in mice, suggesting a valuable effect of chia oil supplementation in regulating inflammatory responses and some immune functions during immune-mediated inflammatory disorders (IMID). Nonetheless, additional reports will need to assess the effect of chia oil in well-controlled clinical trials performed in MS patients.


Assuntos
Anti-Inflamatórios , Extratos Vegetais , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Carragenina , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/prevenção & controle , Humanos , Mediadores da Inflamação , Camundongos , Extratos Vegetais/uso terapêutico
2.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638973

RESUMO

The search for promising biomolecules such as chitooligosaccharides (COS) has increased due to the need for healing products that act efficiently, avoiding complications resulting from exacerbated inflammation. Therefore, this study aimed to produce COS in two stages of hydrolysis using chitosanases derived from Bacillus toyonensis. Additionally, this study aimed to structurally characterize the COS via mass spectrometry, to analyze their biocompatibility in acute toxicity models in vivo, to evaluate their healing action in a cell migration model in vitro, to analyze the anti-inflammatory activity in in vivo models of xylol-induced ear edema and zymosan-induced air pouch, and to assess the wound repair action in vivo. The structural characterization process pointed out the presence of hexamers. The in vitro and in vivo biocompatibility of COS was reaffirmed. The COS stimulated the fibroblast migration. In the in vivo inflammatory assays, COS showed an antiedematogenic response and significant reductions in leukocyte migration, cytokine release, and protein exudate. The COS healing effect in vivo was confirmed by the significant wound reduction after seven days of the experiment. These results indicated that the presence of hexamers influences the COS biological properties, which have potential uses in the pharmaceutical field due to their healing and anti-inflammatory action.


Assuntos
Anti-Inflamatórios/administração & dosagem , Materiais Biocompatíveis/administração & dosagem , Quitosana/administração & dosagem , Otopatias/tratamento farmacológico , Edema/tratamento farmacológico , Oligossacarídeos/administração & dosagem , Cicatrização/efeitos dos fármacos , Células 3T3 , Animais , Anti-Inflamatórios/química , Bacillus/enzimologia , Materiais Biocompatíveis/química , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Citocinas/metabolismo , Modelos Animais de Doenças , Otopatias/induzido quimicamente , Edema/induzido quimicamente , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Glicosídeo Hidrolases/química , Hidrólise , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Oligossacarídeos/química
3.
Molecules ; 26(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34641627

RESUMO

Peganum harmala (P. harmala) belongs to the family Zygophyllaceae, and is utilized in the traditional medicinal systems of Pakistan, China, Morocco, Algeria, and Spain to treat several chronic health disorders. The aim of the present study was to identify the chemical constituents and to evaluate the antioxidant, anti-inflammatory, and toxicity effects of P. harmala extracts both in vitro and in vivo. Sequential crude extracts including 100% dichloromethane, 100% methanol, and 70% aqueous methanol were obtained and their antioxidant and anti-inflammatory effects evaluated both in vitro and in vivo. The anti-inflammatory effect of the extract was investigated using the carrageenan-induced paw edema method in mice, whereas the toxicity of the most active extract was evaluated using an acute and subacute toxicity rat model. In addition, we have used the bioassay-guided approach to obtain potent fractions, using solvent-solvent partitioning and reversed phase high performance liquid chromatography from active crude extracts; identification and quantification of compounds from the active fractions was achieved using electrospray ionization mass spectrometry and high performance liquid chromatography techniques. Results revealed that the 100% methanol extract of P. harmala exhibits significant in vitro antioxidant activity in DPPH assay with an IC50 of 49 µg/mL as compared to the standard quercetin with an IC50 of 25.4 µg/mL. The same extract exhibited 63.0% inhibition against serum albumin denaturation as compared to 97% inhibition by the standard diclofenac sodium in an in vitro anti-inflammatory assay, and in vivo anti-inflammatory against carrageenan-induced paw edema (75.14% inhibition) as compared to 86.1% inhibition caused by the standard indomethacin. Furthermore, this extract was not toxic during a 14 day trial of acute toxicity when given at a dose of 3 g/kg, indicating that the lethal dose (LD50) of P. harmala methanol extract was greater than 3 g/kg. P. harmala methanolic fraction 2 obtained using bioassay-guided fractionation showed the presence of quinic acid, peganine, harmol, harmaline, and harmine, confirmed by electrospray ionization mass spectrometry and quantified using external standards on high performance liquid chromatography. Taken all together, the current investigation further confirms the antioxidant, anti-inflammatory, and safety aspects of P. harmala, which justifies its use in folk medicine.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Carragenina/efeitos adversos , Edema/tratamento farmacológico , Peganum/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Modelos Animais de Doenças , Edema/induzido quimicamente , Indometacina/farmacologia , Dose Letal Mediana , Camundongos , Extratos Vegetais/química , Quercetina/farmacologia , Ratos , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda
4.
Molecules ; 26(19)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34641376

RESUMO

Different parts of Araucaria bidiwillii (bunya pin) trees, such as nuts, seeds, bark, and shoots, are widely used in cooking, tea, and traditional medicines around the world. The shoots essential oil (EO) has not yet been studied. Herein, the chemical profile of A. bidiwillii shoots EO (ABSEO) was created by GC-MS analysis. Additionally, the in vivo oral and topical anti-inflammatory effect against carrageenan-induced models, as well as antipyretic potentiality of ABSEO and its nanoemulsion were evaluated. Forty-three terpenoid components were identified and categorized as mono- (42.94%), sesqui- (31.66%), and diterpenes (23.74%). The main compounds of the ABSEO were beyerene (20.81%), α-pinene (16.21%), D-limonene (14.22%), germacrene D (6.69%), ß-humulene (4.14%), and sabinene (4.12%). The ABSEO and its nanoemulsion exhibited significant inflammation suppression in carrageenan-induced rat paw edema model, in both oral (50 and 100 mg/kg) and topical (5% in soyabean oil) routes, compared to the control and reference drugs groups. All the results demonstrated the significant inflammation reduction via the inflammatory cytokines (IL-1ß and IL8), nitrosative (NO), and prostaglandin E2 (PGE2) supported by the histopathological studies and immunohistochemical assessment of MMP-9 and NF-κß levels in paw tissues. Moreover, the oral administration of ABSEO and its nanoemulsion (50 and 100 mg/kg) exhibited antipyretic activity in rats, demonstrated by the inhibition of hyperthermia induced by intramuscular injection of brewer's yeast. These findings advised that the use of ABSEO and its nanoemulsion against numerous inflammatory and hyperthermia ailments that could be attributed to its active constituents.


Assuntos
Anti-Inflamatórios/farmacologia , Antipiréticos/farmacologia , Araucaria/química , Edema/tratamento farmacológico , Febre/tratamento farmacológico , Inflamação/tratamento farmacológico , Óleos Voláteis/farmacologia , Animais , Carragenina/efeitos adversos , Edema/induzido quimicamente , Edema/patologia , Emulsões , Inflamação/induzido quimicamente , Inflamação/patologia , Masculino , Dor/tratamento farmacológico , Extratos Vegetais/farmacologia , Brotos de Planta/química , Ratos , Ratos Wistar
5.
Am J Case Rep ; 22: e931960, 2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34537806

RESUMO

BACKGROUND The strong association between type 2 diabetes and obesity has been well recognized. Insulin treatment is usually needed at some point in the treatment of patients with type 2 diabetes and obesity to achieve the targeted glycemic control goal. CASE REPORT A 35-year-old woman who had gastric banding for morbid obesity 1 year prior presented to the outpatient clinic with recent onset of shortness of breath and bilateral ankle edema, which were thought to be of cardiac origin. Band slippage occurred a few months after the procedure, and the patient gained weight rapidly thereafter. She had been diagnosed with type 2 diabetes mellitus 8 years earlier, which was treated with oral hypoglycemic medication. Thyroid function tests done 4 months prior to her current presentation revealed normal results. A cardiac assessment showed normal cardiac function with no evidence of heart failure. Repeated thyroid function testing showed new-onset subclinical hypothyroidism. The patient had started insulin therapy 2 weeks before her current presentation, which was probably the main cause of her edema. While continuing insulin, the patient's general condition improved with diuretics therapy, following which she had gastric bypass surgery. CONCLUSIONS Insulin-induced edema is an under-diagnosed problem. It should be considered whenever a patient with uncontrolled diabetes develops rapid body swelling after initiation of insulin therapy. Rigorous research is needed to explore the pathophysiology, prevalence, and treatment of insulin-induced edema.


Assuntos
Diabetes Mellitus Tipo 2 , Obesidade Mórbida , Adulto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Edema/induzido quimicamente , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Obesidade Mórbida/complicações
6.
Zhongguo Zhong Yao Za Zhi ; 46(12): 3034-3042, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467693

RESUMO

To explore the mechanism of anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium based on network pharmacology and inflammatory or pain mouse models. The effective components of Zanthoxyli Pericarpium were screened out by TCMSP database. And their potential corresponding targets were predicted by PharmMapper software. The possible targets relating to inflammation and pain were mainly collected through DrugBank, TTD and DisGeNET databases. The "active ingredient-gene-disease" network diagram was constructed by Cytoscape 3.7.0 software. The network pharmacology results showed 5 potential effective compounds, which were related to 29 targets; 132 targets relating to inflammation and pain were screened out in the DrugBank, TTD and DisGeNET databases. The network analysis results indicated that the phosphatidylinositol 3-kinase catalytic subunit gamma isoform(PIK3 CG) gene may be the key to the anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium. The anti-inflammatory and analgesic effects of essential oil extract and dichloromethane extract of Zanthoxyli Pericarpium were explored through the mouse model of inflammation induced by xylene or carrageenan and the mouse model of pain induced by acetic acid or formalin. The experimental results showed that essential oil extract and dichloromethane extract of Zanthoxyli Pericarpium could reduce xylene-induced ear swelling and carrageenan-induced paw swelling and decrease the number of writhing responses in mice induced by acetic acid and the licking foot time of mice in phase Ⅱ induced by formalin. Western blot results showed that Zanthoxyli Pericarpium extract could inhibit the expressions of PIK3 CG, phosphonated nuclear factor kappaB(p-NF-κB) and phosphonated p38(p-p38 MAPK) protein. The present study showed the anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium through multiple components and targets, so as to provide a pharmacodynamic basis for the study of Zanthoxyli Pericarpium and its mechanism.


Assuntos
Medicamentos de Ervas Chinesas , Óleos Voláteis , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Inflamação/tratamento farmacológico , Inflamação/genética , Camundongos , Extratos Vegetais
8.
Biomed Res Int ; 2021: 5536030, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395619

RESUMO

Argania spinosa (L.) plays an important role in the Moroccan agroeconomy, providing both employment and export revenue. Argan oil production generates different by-products with functionalities that are not yet investigated, in particular, the shell fruit. The present study aims, for the first time, at evaluating the acute and subacute toxicity, anti-inflammatory, and antioxidant effects of argan fruit shell ethanol extract (AFSEE). The LD50 of AFSEE was determined to be greater than the 5000 mg/kg body weight of mice. No significant variation in the body and organ weights was observed after 28 days of AFSEE treatment compared to that of the control group. Biochemical parameters and histopathological examination revealed no toxic effects of AFSEE. The AFSEE produced a significant inhibition of xylene-induced ear edema in mice. AFSEE reduced significantly the paw edema in mice after carrageenan injection. The chemical characterization showed that AFSEE contains a high level of total phenol content, flavonoids, condensed tannins, and flavanols. The obtained IC50 of DPPH, ABTS, reducing power, and ß-carotene demonstrates that AFSEE has a potential antioxidant effect. The results indicate that AFSEE was safe and nontoxic to mice even at higher doses. Furthermore, the present findings demonstrate that AFSEE has potential anti-inflammatory and antioxidant activities.


Assuntos
Álcoois/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Edema/tratamento farmacológico , Sapotaceae/química , Xilenos/toxicidade , Álcoois/química , Álcoois/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Dose Letal Mediana , Masculino , Camundongos , Marrocos , Extratos Vegetais/química
9.
J Histochem Cytochem ; 69(8): 511-522, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34291686

RESUMO

Induction of severe inflammatory arthritis in the collagen antibody-induced arthritis (CAIA) murine model causes extensive joint damage and pain-like behavior compromising analysis. While mild models are less severe, their reduced, variable penetrance makes assessment of treatment efficacy difficult. This study aimed to compare macroscopic and microscopic changes in the paws, along with central nervous system activation between a mild and moderate CAIA model. Balb/c mice (n=18) were allocated to control, mild, and moderate CAIA groups. Paw inflammation, bone volume (BV), and paw volume (PV) were assessed. Histologically, the front paws were assessed for joint inflammation, cartilage damage, and pre/osteoclast-like cells and the lumbar spinal cord and the periaqueductal gray (PAG) region of the brain for glial reactivity. A moderate CAIA dose induced (1) significantly greater local paw inflammation, inflammatory cell infiltration, and PV; (2) significantly more osteoclast-like cells on the bone surface and within the surrounding soft tissue; and (3) significantly greater glial reactivity within the PAG compared with the mild CAIA model. These findings support the use of a moderate CAIA model (higher dose of monoclonal antibodies with low-dose lipopolysaccharide) to induce more consistent histopathological features, without excessive joint destruction.


Assuntos
Artrite Experimental/patologia , Reabsorção Óssea/patologia , Cartilagem Articular/patologia , Modelos Animais de Doenças , Edema/patologia , Animais , Anticorpos Monoclonais/administração & dosagem , Artrite Experimental/induzido quimicamente , Artrite Experimental/diagnóstico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/patologia , Reabsorção Óssea/induzido quimicamente , Reabsorção Óssea/diagnóstico , Cartilagem Articular/efeitos dos fármacos , Edema/induzido quimicamente , Edema/diagnóstico , Feminino , Membro Anterior/efeitos dos fármacos , Membro Anterior/patologia , Histocitoquímica , Lipopolissacarídeos/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Neuroglia/efeitos dos fármacos , Neuroglia/patologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/patologia , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Substância Cinzenta Periaquedutal/patologia , Índice de Gravidade de Doença , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia
10.
Molecules ; 26(14)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34299559

RESUMO

The pineal gland is a neuroendocrine organ that plays an important role in anti-inflammation through the hormone melatonin. The anti-inflammatory effects of melatonin and its derivatives have been reported in both in vitro and in vivo models. Our previous study reported the potent antioxidant and neuroprotective activities of bromobenzoylamide substituted melatonin. In silico analysis successfully predicted that melatonin bromobenzoylamid derivatives were protected from metabolism by CYP2A1, which is a key enzyme of the melatonin metabolism process. Therefore, the anti-inflammatory activities of melatonin and its bromobenzoylamide derivatives BBM and EBM were investigated in LPS-induced RAW 264.7 macrophages and croton oil-induced ear edema in mice. The experiments showed that BBM and EBM significantly reduced production of the inflammatory mediators interleukin-6 (IL-6), prostaglandin E2 (PGE2), and nitric oxide (NO) in a dose-dependent manner, but only slightly affected TNF-α in LPS-induced RAW 264.7 macrophages. This suggests that modifying melatonin at either the N1-position or the N-acetyl side chain affected production of NO, PGE2 and IL-6 in in vitro model. In the croton oil-induced mouse ear edema model, BBM, significantly decreased ear edema thickness at 2-4 h. It leads to conclude that bromobenzoylamide derivatives of melatonin may be one of the potential candidates for a new type of anti-inflammatory agent.


Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Melatonina/análogos & derivados , Melatonina/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Benzoatos/química , Benzoatos/farmacologia , Óleo de Cróton , Edema/induzido quimicamente , Halogenação , Lipopolissacarídeos , Masculino , Melatonina/uso terapêutico , Camundongos , Camundongos Endogâmicos ICR , Células RAW 264.7
11.
Eur J Med Chem ; 224: 113682, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34245948

RESUMO

Addressing the global need for the development of safe and potent NSAIDs, new series of oxadiazolo and thiadiazolo fused pyrmidinones were synthesized and initially tested for their analgesic activity. All tested compounds showed promising analgesic activity compared with the reference standard indomethacin. Moreover, anti-inflammatory activity evaluation, ulcerogenic liability, and in vitro COX-1, COX-2 enzyme inhibition assays were also performed for the most active derivatives. The methoxyphenyl piperazinyl derivative 3d showed analgesic activity surpassing indomethacin with protection of 100%, and 83%; respectively. Also 3d showed good anti-inflammatory activity with relatively lower ulcer index compared with other tested compounds, and potent COX-1 and COX-2 inhibitory activity with IC50 = 0.140, 0.007 µm, respectively, and with a selectivity index of 20.00 which was better than the reference standards and the other tested congeners. Additionally, compounds 3b, 3g and 3h revealed moderate selectivity (SI = 3.53, 3.70 and 5.87, respectively). Moreover, in silico physicochemical parameters revealed that the new fused pyrimidinones demonstrated promising pharmacokinetic properties. Furthermore, computational studies in form of 2D-quantitative structure-activity relationship (2D-QSAR) and 3D-pharmacophore confirmed the potential analgesic properties of the new target compounds.


Assuntos
Analgésicos/química , Anti-Inflamatórios/química , Ciclo-Oxigenase 2/metabolismo , Pirimidinonas/química , Analgésicos/metabolismo , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Ciclo-Oxigenase 1/química , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Modelos Animais de Doenças , Desenho de Fármacos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/patologia , Humanos , Masculino , Camundongos , Pirimidinonas/metabolismo , Pirimidinonas/uso terapêutico , Relação Quantitativa Estrutura-Atividade , Ratos , Ratos Wistar
12.
Curr Protoc ; 1(7): e202, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34314105

RESUMO

Animal models of inflammation are used to assess the production of inflammatory mediators at sites of inflammation, the processing of pain sensation at CNS sites, the anti-inflammatory properties of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs), and the efficacy of putative analgesic compounds in reversing cutaneous hypersensitivity. Detailed in this article are methods to elicit and measure carrageenan- and complete Freund's adjuvant (CFA)-induced cutaneous inflammation. Due to possible differences between the dorsal root sensory system and the trigeminal sensory system, injections into either the footpad or vibrissal pad are described. In this manner, cutaneous inflammation can be assessed in tissue innervated by the lumbar dorsal root ganglion neurons (footpad) or by the trigeminal ganglion neurons (vibrissal pad). © 2021 Wiley Periodicals LLC.


Assuntos
Edema , Hipersensibilidade , Animais , Carragenina/toxicidade , Edema/induzido quimicamente , Adjuvante de Freund/toxicidade , Inflamação/induzido quimicamente , Ratos
13.
Biomed Pharmacother ; 139: 111635, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243601

RESUMO

This study aimed to evaluate the anti-inflammatory effect of Auraptene (AUR) and Umbelliprenin (UMB) in a rat model of rheumatoid arthritis (RA) induced by using complete Freund's adjuvant (CFA). Paw swelling of adjuvant arthritis rats measured at various times after CFA injection. Over 15 days of RA induction, mediator/cytokine-mediated processes involved in managing the regulation and resolving RA's inflammation were also quantified with ELISA. Histopathological changes were also assessed under a microscope 15 days after the CFA injection. AUR at all doses and UMB administration only at a 16 mM /kg administration dose significantly reduced CFA-induced paw edema level compared to the control group. UMB (64 and 32 mM) and AUR (64, 32, and 16 mM) could reduce the PGE2 (p < .0001-.01) and NO (p < .0001-.05) levels in the treatment groups compared to the negative control group. However, these compounds showed no significant effect on the TNF-α, IFN-γ, TGF-ß, IL-4, and IL-10 levels than the control group (p > .05). Unlike indomethacin and prednisolone, treatment of rats with AUR (16, 32, and 64 mM/kg) and UMB (16 and 32 mM/kg) reduced the level of IL-2 (p < .0001). In all treatment groups, the serum level of IL-17 was significantly reduced compared to the CFA group (p < .001-0.05). We suggested AUR and UMB could diminish inflammation by reducing the serum level of IL-17 and could be considered a proper alternative in the treatment of IL-17 related inflammatory diseases such as rheumatoid arthritis. Given that AUR and UMB apply their anti-inflammatory effects by changing distinct cytokine release/inhibition patterns, their potential application in diverse inflammatory diseases seems different.


Assuntos
Artrite/tratamento farmacológico , Cumarínicos/farmacologia , Adjuvante de Freund/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Substâncias Protetoras/farmacologia , Umbeliferonas/farmacologia , Administração Oral , Animais , Anti-Inflamatórios/farmacologia , Artrite/metabolismo , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Citocinas/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Inflamação/metabolismo , Masculino , Ratos , Ratos Wistar
14.
BMJ Case Rep ; 14(7)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34301698

RESUMO

Insulin oedema is a rare complication of insulin treatment characterised by an absence of heart, liver and renal involvement. Insulin oedema typically develops in the lower extremities or, less frequently, as generalised oedema after initiation of insulin therapy. We report a 59-year-old man with poorly controlled type 2 diabetes who developed oedema in his penis and scrotum accompanied by weight gain following intensive insulin therapy. His oedema improved after reduction of the daily insulin injection dose and treatment for urinary retention. Penile and scrotal oedema is a rare physical finding for the patient with diabetes. Therefore, in patients with poorly controlled diabetes who have started insulin therapy, physicians should pay attention to urinary retention and do not miss changes in weight gain or oedema in the lower body, including the perineal region.


Assuntos
Diabetes Mellitus Tipo 2 , Retenção Urinária , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Edema/induzido quimicamente , Humanos , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pênis , Escroto , Retenção Urinária/induzido quimicamente
15.
Molecules ; 26(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34205060

RESUMO

The medicinal potential and volatile composition of different parts of three cultivars of grapefruit (Citrus paradisi) were evaluated for their toxicity and anti-inflammatory activities. Fresh leaf and fruit peel were separately isolated by hydrodistillation for 4 h. The essential oils were subjected to GC/GC-MS analysis for chemical profile. Toxicity of the essential oils in mice were evaluated using Lorke's method, while an anti-inflammatory assay was performed in a rat model using egg albumin-induced oedema. The oils obtained were light yellow in colour, and odour varied from strong citrus smell to mild. Percentage yield of fresh peel oil (0.34-0.57%) was greater than the fresh leaf oil yield (0.21-0.34%). D-limonene (86.70-89.90%) was the major compound identified in the leaf oil, while ß-phellandrene (90.00-91.01%) dominated the peel oil. At a dosage level of 5000 mg/kg, none of the oils showed mortality in mice. An anti-inflammatory bioassay revealed that all the oils caused a significant (p < 0.05-0.01) reduction in oedema size when compared to the negative control group throughout the 5 h post induction assessment period. The study reveals that the oils are non-toxic and demonstrate significant anti-inflammatory activity. Our findings suggest that the leaf and peel oils obtained from waste parts of grapefruit plants can be useful as flavouring agents, as well as anti-inflammatory agents.


Assuntos
Anti-Inflamatórios/administração & dosagem , Citrus paradisi/química , Edema/tratamento farmacológico , Óleos Voláteis/administração & dosagem , Ovalbumina/efeitos adversos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Monoterpenos Cicloexânicos/análise , Modelos Animais de Doenças , Edema/induzido quimicamente , Frutas/química , Cromatografia Gasosa-Espectrometria de Massas , Limoneno/análise , Camundongos , Estrutura Molecular , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Folhas de Planta/química , Óleos Vegetais/análise , Óleos Vegetais/química , Ratos , África do Sul
16.
Bioorg Chem ; 113: 105023, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34091292

RESUMO

Fifteen new water-soluble alkaloids were obtained from the fresh herbs of Portulaca oleracea L. The structures of 15 alkaloids 1-15 were established according to spectroscopic data, and the stereoconfigurations were determined based on experimental and calculated electronic circular dichroism (ECD) data and single crystal X-ray diffraction. Alkaloids 1-15 were found to display good anti-inflammatory activity at 10 µM and could significantly reduce the interleukin-6 (IL-6) and nitric oxide (NO) levels induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages.


Assuntos
Alcaloides/química , Anti-Inflamatórios/química , Portulaca/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Cristalografia por Raios X , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/patologia , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Conformação Molecular , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Portulaca/metabolismo , Células RAW 264.7 , Solubilidade , Água/química
18.
J Med Chem ; 64(13): 9550-9566, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34137625

RESUMO

Preclinical and clinical data reveal that inflammation is strongly correlated with the pathogenesis of a number of diseases including those of cancer, Alzheimer, and diabetes. The inflammatory cascade involves a multitude of cytokines ending ultimately with the activation of COX-2/LOX for the production of prostaglandins and leukotrienes. While the available inhibitors for these enzymes suffer from nonoptimal selectivity, in particular for COX-2, we present here the results of purposely designed tartarate derivatives that exhibit favorable selectivity and significant effectiveness against COX-2 and LOX. Integrated approaches of molecular simulation, organic synthesis, and biochemical/physical experiments identified 15 inhibiting COX-2 and LOX with respective IC50 4 and 7 nM. At a dose of 5 mg kg-1 to Swiss albino mice, 15 reversed algesia by 65% and inflammation by 33% in 2-3 h. We find good agreement between experiments and simulations and use the simulations to rationalize our observations.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Desenho de Fármacos , Edema/tratamento farmacológico , Inibidores de Lipoxigenase/farmacologia , Tartaratos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Carragenina , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Feminino , Humanos , Lipoxigenase/metabolismo , Inibidores de Lipoxigenase/síntese química , Inibidores de Lipoxigenase/química , Masculino , Camundongos , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-Atividade , Tartaratos/síntese química , Tartaratos/química
19.
Int J Mol Sci ; 22(9)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064436

RESUMO

2-Arachidonyl-lysophosphatidylethanolamine, shortly 2-ARA-LPE, is a polyunsaturated lysophosphatidylethanolamine. 2-ARA-LPE has a very long chain arachidonic acid, formed by an ester bond at the sn-2 position. It has been reported that 2-ARA-LPE has anti-inflammatory effects in a zymosan-induced peritonitis model. However, it's action mechanisms are poorly investigated. Recently, resolution of inflammation is considered to be an active process driven by M2 polarized macrophages. Therefore, we have investigated whether 2-ARA-LPE acts on macrophages for anti-inflammation, whether 2-ARA-LPE modulates macrophage phenotypes to reduce inflammation, and whether 2-ARA-LPE is anti-inflammatory in a carrageenan-induced paw edema model. In mouse peritoneal macrophages, 2-ARA-LPE was found to inhibit lipopolysaccharide (LPS)-induced M1 macrophage polarization, but not induce M2 polarization. 2-ARA-LPE inhibited the inductions of inducible nitric oxide synthase and cyclooxygenase-2 in mouse peritoneal macrophages at the mRNA and protein levels. Furthermore, products of the two genes, nitric oxide and prostaglandin E2, were also inhibited by 2-ARA-LPE. However, 1-oleoyl-LPE did not show any activity on the macrophage polarization and inflammatory responses. The anti-inflammatory activity of 2-ARA-LPE was also verified in vivo in a carrageenan-induced paw edema model. 2-ARA-LPE inhibits LPS-induced M1 polarization, which contributes to anti-inflammation and suppresses the carrageenan-induced paw edema in vivo.


Assuntos
Anti-Inflamatórios/farmacologia , Ácidos Araquidônicos/farmacologia , Edema/tratamento farmacológico , Lisofosfolipídeos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Ácidos Araquidônicos/química , Carragenina/administração & dosagem , Ciclo-Oxigenase 2/imunologia , Dinoprostona/antagonistas & inibidores , Dinoprostona/biossíntese , Edema/induzido quimicamente , Edema/imunologia , Edema/patologia , Membro Posterior/efeitos dos fármacos , Membro Posterior/imunologia , Membro Posterior/metabolismo , Subunidade p35 da Interleucina-12/antagonistas & inibidores , Subunidade p35 da Interleucina-12/imunologia , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/imunologia , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Lisofosfolipídeos/química , Macrófagos Peritoneais/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/imunologia , Cultura Primária de Células , Resultado do Tratamento
20.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068193

RESUMO

In this study, we investigate the immunomodulatory effects of a novel antimicrobial peptide, YD1, isolated from Kimchi, in both in vitro and in vivo models. We establish that YD1 exerts its anti-inflammatory effects via up-regulation of the Nrf2 pathway, resulting in the production of HO-1, which suppresses activation of the NF-κB pathway, including the subsequent proinflammatory cytokines IL-1ß, IL-6, and TNF-α. We also found that YD1 robustly suppresses nitric oxide (NO) and prostaglandin E2 (PGE2) production by down-regulating the expression of the upstream genes, iNOS and COX-2, acting as a strong antioxidant. Collectively, YD1 exhibits vigorous anti-inflammatory and antioxidant activity, presenting it as an interesting potential therapeutic agent.


Assuntos
Anti-Inflamatórios/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Inflamação/prevenção & controle , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Citotóxicas Formadoras de Poros/farmacologia , Animais , Citocinas/metabolismo , Edema/induzido quimicamente , Edema/metabolismo , Edema/patologia , Edema/prevenção & controle , Heme Oxigenase-1/genética , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Lipopolissacarídeos/toxicidade , Proteínas de Membrana/genética , Camundongos , Fator 88 de Diferenciação Mieloide/antagonistas & inibidores , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...