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1.
Biomed Pharmacother ; 112: 108624, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30784921

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease of synovial inflammation and joint destruction. This study reports anti-arthritic potential of opuntioside-I opuntiol, and its gold and silver nanoparticles (NPs) against Complete Freund's Adjuvant (CFA)-induced arthritic rats. The mechanistic studies were performed targeting TLRs (TLR-2 and TLR-4) and cytokines (IL-1ß and TNF-α) expressions to validate their anti-inflammatory and immuno-modulatory response. The nano-formulations were successfully characterized employing Atomic Force Microscopy (AFM) and Dynamic Light Scattering (DLS) analysis. Opuntiol and opuntioside (OP and OPG: 10, 50 and 100 mg/kg) and opuntiol-coated silver and gold NPs (OP-AgNPs and OP-AuNPs: 0.5, 1 and 3 mg/kg) treatments in arthritic rat have shown minimal arthritic score exhibiting mild to moderate articular changes and tissue swelling in ankle joints. Radiographic examination reveals significant reduction in synovitis with improvement in joints degenarative changes in the presence of aforementioned treatments. Likewise, histology of rat ankle joints depicted comparatively lesser influx of inflammatory cells and diminished granulamatous inflammation. Moreover, treatment groups suppressed protein and mRNA expressions of TLRs (TLR-2 and TLR-4) and cytokines (IL-1ß and TNF-α) levels were also significantly declined in the presence of OPG, OP and its NPs comparing to arthritic control. This investigation concludes, the tested compounds and nano-formulations successfully restored the disease progression in CFA-induced arthritic rat owing to their immunomodulatory and anti-inflammatory potentials and can be considered for RA targeted therapy to address the utmost challenges of the disease.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Ácidos Cumáricos/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Monossacarídeos/uso terapêutico , Receptor 2 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/antagonistas & inibidores , Animais , Antirreumáticos/administração & dosagem , Antirreumáticos/química , Artrite Experimental/imunologia , Artrite Experimental/metabolismo , Ácidos Cumáricos/administração & dosagem , Ácidos Cumáricos/química , Feminino , Adjuvante de Freund , Ouro/química , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Monossacarídeos/administração & dosagem , Monossacarídeos/química , Ratos Wistar , Prata/química
2.
J Ethnopharmacol ; 182: 221-34, 2016 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-26900126

RESUMO

ETHANOPHARMACOLOGICAL RELEVANCE: Opuntia dillenii Haw (Nagphana) traditionally used against inflammation. The present study addressed the anti-inflammatory activity of O. dillenii derived methanol extract, fractions and pure compounds and their underlying mechanism of action. MATERIALS AND METHODS: O. dillenii cladode methanol extract was subjected to vacuum liquid chromatography (VLC) furnishing two main fractions viz (T-1 and -2) leading to isolation of opuntiol (aglycone) and opuntioside (O-glucoside), respectively. Anti-inflammatory activity of extract, fractions, pure compounds and reference drugs were evaluated using: (1) arachidonic acid (AA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced ear edema accompanied by histological studies of mice ear sections and phospholipase A2 (PLA2)-induced mice paw edema. (2) Carrageenan and glycogen-induced peritonitis in rodents. In parallel levels of leukotriene B4 (LTB4) and reactive oxygen species (ROS) were also determined via HPLC and fluoroemetrically using 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA) dye, respectively. Additionally, levels of prostaglandin E2 (PGE2), tumor necrosis factor (TNF-α), interleukins IL-1ß and -6 were measured by ELISA assay. RESULTS: O. dillenii methanol extract, fractions and pure compounds reduced AA and TPA-induced ear punch weight in a dose dependent fashion. The corresponding IC50 values obtained also suppressed inflammatory features observed histologically. Furthermore, paw edema and peritonitis were also attenuated. Similar to indomethacin and diclofenac sodium, opuntioside reduced PGE2 levels of inflamed ear which was comparatively 1.3× better than opuntiol. However, opuntiol was more potent in reducing LTB4 levels in rat neutrophils with an IC50 value of 19±3.3µΜ, while opuntioside was ineffective. Opuntiol also effectively suppressed ROS (37%) and cytokine levels (TNF-α, IL-1ß and -6) by ~50% and comparable to dexamethasone. CONCLUSIONS: O. dillenii cladodes possess anti-inflammatory properties via inhibition of arachidonic acid metabolites and cytokines. Opuntiol (aglycone) emerged as a dual inhibitor of cyclooxygenase (COX) and lipooxygenase (LOX) pathways. It also suppressed ROS and cytokine levels. However, opuntioside manifested its selectivity towards COX (PGE2) pathway without affecting LTB4 levels. The present report describing the anti-inflammatory activity of opuntiol and opuntioside for the first time thereby, supporting and justifying the traditional use of O. dillenii against inflammation and may serve as lead compound in designing of new anti-inflammatory agents.


Assuntos
Anti-Inflamatórios/uso terapêutico , Ácidos Cumáricos/uso terapêutico , Edema/tratamento farmacológico , Monossacarídeos/uso terapêutico , Opuntia , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Ácido Araquidônico , Permeabilidade Capilar/efeitos dos fármacos , Carragenina , Ácidos Cumáricos/análise , Ácidos Cumáricos/farmacologia , Citocinas/metabolismo , Dinoprostona/metabolismo , Orelha/patologia , Edema/induzido quimicamente , Edema/metabolismo , Feminino , Pé/patologia , Leucotrieno B4/metabolismo , Masculino , Camundongos , Monossacarídeos/análise , Monossacarídeos/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Fosfolipases A2 , Fitoterapia , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Acetato de Tetradecanoilforbol
3.
Biol Pharm Bull ; 28(10): 1844-51, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16204933

RESUMO

Methanolic extract of Opuntia dillenii cladodes and its pure compound alpha-pyrone glycoside, opuntioside-I showed potent hypotensive activity in normotensive rats. Both the extract and opuntioside-I showed comparable effect of 44-54% fall in Mean Arterial Blood Pressure (MABP) at the dose of 10 mg/kg. No mortality was observed in rats even at the doses of 1000 mg/kg/d and 900 mg/kg/d per oral of extract and opuntioside-I respectively. However, histopathology revealed adverse effects of high doses on liver and spleen of the experimental animals.


Assuntos
Anti-Hipertensivos/farmacologia , Monossacarídeos/farmacologia , Opuntia/química , Extratos Vegetais/farmacologia , Animais , Anti-Hipertensivos/toxicidade , Bilirrubina/sangue , Glicemia/análise , Proteínas Sanguíneas/análise , Colesterol/sangue , Monossacarídeos/toxicidade , Extratos Vegetais/toxicidade , Ratos , Baço/efeitos dos fármacos , Baço/patologia
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