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1.
J Ayurveda Integr Med ; 14(5): 100776, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37722234

RESUMO

BACKGROUND: Psidium guajava L (Guava) belongs to the Myrtaceae family and has been claimed to possess several pharmacological properties including antidiabetic. OBJECTIVE: This study was designed to evaluate the anti-hyperglycemic activity of P guajava L leaves aqueous extract on neonatal streptozotocin-induced type 2 diabetic model rats. METHODS: Streptozotocin was induced (90 mg/kg) intraperitoneally to 48 h old Long Evans rat pups. After three months, 18 male type-2 diabetic model rats were confirmed by OGTT (FG > 7 mmol/L). Therefore, experimental rats were divided into three groups 2) Diabetic water control (10 ml/kg), 3) Gliclazide treated (20 mg/kg), and 4) Extract treated group (1.25g/kg)] Six normal female rats comprised group 1 [Non-diabetic water control (10 ml/kg)]. All rats were treated orally with their respective treatment for 28 consecutive days. Blood samples were collected on 0 days (by tail cut method) and the end day (by cardiac puncture) of the experiment. The anti-hyperglycemic activity was evaluated by measuring fasting glucose, serum insulin, lipid profile, hepatic glycogen content, and intestinal glucose absorption by standard methods. RESULTS: The serum glucose level of extract treated group was decreased by 16% as well as significantly (p<0.05) increased the serum insulin level (M±SD, 0 day vs 28thday; 0.319 ± 0.110 vs 0.600 ± 0.348, µg/L). Moreover, the extract-treated group also significantly (p<0.05) enhanced liver glycogen content and inhibited glucose absorption from the upper intestine. Besides, a significant (p < 0.05) reduction of LDL-cholesterol level was found in the extract-treated group (M±SD, 55 ± 33 vs 14 ± 9, mg/dl) compared with baseline values where other groups did not show any statistically remarkable changes. CONCLUSION: Current study concludes that P guajava leaves aqueous extract enhances insulin secretion from pancreatic beta-cells and promotes glycogen synthesis in the liver. The extract also inhibits glucose absorption from the upper intestine and improves dyslipidemia to some extent. Therefore, possesses the potential for drug development against T2DM.

2.
Toxicol Sci ; 164(1): 101-114, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29660078

RESUMO

Exposure to windblown particulate matter (PM) arising from legacy uranium (U) mine sites in the Navajo Nation may pose a human health hazard due to their potentially high metal content, including U and vanadium (V). To assess the toxic impact of PM derived from Claim 28 (a priority U mine) compared with background PM, and consider the putative role of metal species U and V. Two representative sediment samples from Navajo Nation sites (Background PM and Claim 28 PM) were obtained, characterized in terms of chemistry and morphology, and fractioned to the respirable (≤ 10 µm) fraction. Mice were dosed with either PM sample, uranyl acetate, or vanadyl sulfate via aspiration (100 µg), with assessments of pulmonary and vascular toxicity 24 h later. Particulate matter samples were also examined for in vitro effects on cytotoxicity, oxidative stress, phagocytosis, and inflammasome induction. Claim 28 PM10 was highly enriched with U and V and exhibited a unique nanoparticle ultrastructure compared with background PM10. Claim 28 PM10 exhibited enhanced pulmonary and vascular toxicity relative to background PM10. Both U and V exhibited complementary pulmonary inflammatory potential, with U driving a classical inflammatory cytokine profile (elevated interleukin [IL]-1ß, tumor necrosis factor-α, and keratinocyte chemoattractant/human growth-regulated oncogene) while V preferentially induced a different cytokine pattern (elevated IL-5, IL-6, and IL-10). Claim 28 PM10 was more potent than background PM10 in terms of in vitro cytotoxicity, impairment of phagocytosis, and oxidative stress responses. Resuspended PM10 derived from U mine waste exhibit greater cardiopulmonary toxicity than background dusts. Rigorous exposure assessment is needed to gauge the regional health risks imparted by these unremediated sites.


Assuntos
Coração/efeitos dos fármacos , Exposição por Inalação/efeitos adversos , Pulmão/efeitos dos fármacos , Nanopartículas/toxicidade , Material Particulado/toxicidade , Urânio/toxicidade , Compostos de Vanádio/toxicidade , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Sobrevivência Celular/efeitos dos fármacos , Citocinas/análise , Sedimentos Geológicos/química , Humanos , Pulmão/imunologia , Masculino , Camundongos Endogâmicos C57BL , Mineração , Nanopartículas/análise , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Material Particulado/análise , Células THP-1 , Urânio/análise , Compostos de Vanádio/análise , Vasodilatação/efeitos dos fármacos
3.
Invest Ophthalmol Vis Sci ; 59(1): 31-38, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29302691

RESUMO

Purpose: Metal ions play a key role in exacerbating toxicity associated with oxidative stress and inflammation. This study examines the effects of a formulation containing the metal chelator ethylenediaminetetraacetic acid (EDTA) and permeability enhancer methyl sulfonyl methane (MSM) on the early course of inflammation in endotoxin-induced uveitis (EIU). The proprietary MSM/EDTA formulation of Livionex, Inc., which was used for this study, is covered by several patents and pending patent applications. Methods: EIU was induced by using subcutaneous injection of lipopolysaccharide (LPS) into the thighs of Lewis rats. Treatment consisted of topical application to the eyes of either PBS or eye drops designated as ME that contain EDTA and MSM. Clinical signs of uveitis were monitored at 6 and 24 hours postinjection. Oxidative and inflammatory markers were evaluated by ELISA or immunohistochemistry. Results: Rats treated with ME showed fewer clinical signs of uveitis including reduced miosis, fibrinous exudates, and dilated blood vessels. The aqueous humor of treated rats contained fewer leukocytes, lower protein levels, and less PGE2. Formation of protein adducts with the lipid peroxidation end-product, 4-hydroxynonenal, expression of NF-κB, TNF-α, and MMP-9 were all reduced in rats treated with ME. Conclusions: Our results indicate that ME eye drops downregulate the ocular inflammatory response in LPS treated rats, suggesting that induction of EIU involves metal ions and chelation therapy with ME is a potential treatment for uveitis.


Assuntos
Humor Aquoso/metabolismo , Citocinas/biossíntese , Ácido Edético/uso terapêutico , Estresse Oxidativo , Uveíte/tratamento farmacológico , Animais , Humor Aquoso/efeitos dos fármacos , Quelantes de Cálcio/uso terapêutico , Citocinas/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Ratos , Ratos Endogâmicos Lew , Uveíte/diagnóstico , Uveíte/metabolismo
4.
Free Radic Biol Med ; 52(1): 182-90, 2012 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22067901

RESUMO

Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent antioxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study (U.C. Yadav et al., Free Radic. Biol. Med. 48:1423-1434, 2010) indicates a novel role for benfotiamine in the prevention of bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in murine macrophages. Nevertheless, it remains unclear how benfotiamine mediates anti-inflammatory effects. In this study, we investigated the anti-inflammatory role of benfotiamine in regulating arachidonic acid (AA) pathway-generated inflammatory lipid mediators in RAW264.7 macrophages. Benfotiamine prevented the LPS-induced activation of cPLA2 and release of AA metabolites such as leukotrienes, prostaglandin E2, thromboxane 2 (TXB2), and prostacyclin (PGI2) in macrophages. Further, LPS-induced expression of AA-metabolizing enzymes such as COX-2, LOX-5, TXB synthase, and PGI2 synthase was significantly blocked by benfotiamine. Furthermore, benfotiamine prevented the LPS-induced phosphorylation of ERK1/2 and expression of transcription factors NF-κB and Egr-1. Benfotiamine also prevented the LPS-induced oxidative stress and protein-HNE adduct formation. Most importantly, compared to specific COX-2 and LOX-5 inhibitors, benfotiamine significantly prevented LPS-induced macrophage death and monocyte adhesion to endothelial cells. Thus, our studies indicate that the dual regulation of the COX and LOX pathways in AA metabolism could be a novel mechanism by which benfotiamine exhibits its potential anti-inflammatory response.


Assuntos
Anti-Inflamatórios/farmacologia , Expressão Gênica/efeitos dos fármacos , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Tiamina/análogos & derivados , Animais , Ácido Araquidônico/metabolismo , Adesão Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/antagonistas & inibidores , Dinoprostona/biossíntese , Dinoprostona/metabolismo , Epoprostenol/antagonistas & inibidores , Epoprostenol/biossíntese , Epoprostenol/metabolismo , Proteínas da Matriz Extracelular/antagonistas & inibidores , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Inflamação/genética , Inflamação/metabolismo , Leucotrienos/biossíntese , Leucotrienos/metabolismo , Lipopolissacarídeos/efeitos adversos , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , NF-kappa B/metabolismo , Proteína-Lisina 6-Oxidase/antagonistas & inibidores , Proteína-Lisina 6-Oxidase/genética , Proteína-Lisina 6-Oxidase/metabolismo , Tiamina/farmacologia , Tromboxano B2/antagonistas & inibidores , Tromboxano B2/biossíntese , Tromboxano B2/metabolismo
5.
J Toxicol Environ Health A ; 74(6): 380-91, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21271438

RESUMO

Oxidative stress plays a critical role in cataractogenesis, the leading cause of blindness worldwide. Since transition metals generate reactive oxygen species (ROS) formation, metal chelation therapy has been proposed for treatment of cataracts. However, the effectiveness of most chelators is limited by low tissue penetrability. This study is the first to demonstrate that the topically applied divalent metal chelator ethylenediamine tetraacetic acid (EDTA) combined with the carrier and permeability enhancer methyl sulfonyl methane (MSM) ameliorates both oxidation-induced lens opacification and the associated toxic accumulation of protein-4-hydroxynonenal (HNE) adducts. Both in vitro (rat lens culture) and in vivo (diabetic rats), EDTA-MSM (1) significantly reduced lens opacification by about 40-50%, (2) significantly diminished lens epithelial cell proliferation and fiber cell swelling in early stages of cataract formation in vivo, and (3) notably decreased the levels of protein-HNE adducts. These findings have important implications specifically for the treatment of cataract and generally for other diseases in which oxidative stress plays a key pathogenic role.


Assuntos
Catarata/tratamento farmacológico , Quelantes/uso terapêutico , Terapia por Quelação/métodos , Complicações do Diabetes/tratamento farmacológico , Cristalino/efeitos dos fármacos , Metais/metabolismo , Administração Tópica , Aldeídos/toxicidade , Animais , Catarata/metabolismo , Catarata/patologia , Proliferação de Células/efeitos dos fármacos , Quelantes/administração & dosagem , Quelantes/metabolismo , Complicações do Diabetes/induzido quimicamente , Complicações do Diabetes/patologia , Dimetil Sulfóxido/administração & dosagem , Dimetil Sulfóxido/metabolismo , Dimetil Sulfóxido/uso terapêutico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ácido Edético/administração & dosagem , Ácido Edético/metabolismo , Ácido Edético/uso terapêutico , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Cristalino/ultraestrutura , Masculino , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Sulfonas/administração & dosagem , Sulfonas/metabolismo , Sulfonas/uso terapêutico
6.
Invest Ophthalmol Vis Sci ; 51(10): 5105-13, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20435582

RESUMO

PURPOSE: To investigate the anti-inflammatory effects of guggulsterone, an antioxidant and antitumor agent, in endotoxin-induced uveitis (EIU) in rats and to elucidate the underlying molecular mechanism or mechanisms related to ocular inflammation. METHODS: EIU was induced by subcutaneous injection of lipopolysaccharide (LPS; 150 µg) into Lewis rats treated with guggulsterone (30 mg/kg body weight, intraperitoneally) or its carrier. After 24 hours the rats were killed, eyes were enucleated, and aqueous humor (AqH) was collected. Numbers of infiltrating cells and levels of matrix metalloproteinase-2 (MMP-2), nitric oxide (NO), and prostaglandin E(2) (PGE(2)) were determined in AqH by specific ELISAs. An antibody array was used to measure the expression of various inflammatory cytokines in AqH. The expression of MMP-2, iNOS, Cox-2, phospho-IκB, and phospho-NF-κB was determined immunohistochemically. Human primary nonpigment ciliary epithelial cells (HNPECs) were used to determine the in vitro efficacy of guggulsterone on the LPS-induced inflammatory response. RESULTS: Compared with control, the EIU rat eye AqH had a significantly higher number of infiltrating cells, total protein, and inflammatory markers, such as MMP-2, NO, and PGE(2), and the treatment of guggulsterone prevented EIU-induced increases. Guggulsterone also prevented the expression of MMP-2, iNOS, and Cox-2 proteins and of IκB and NF-κB in various eye tissues. Moreover, in cultured HNPECs, guggulsterone inhibited LPS-induced expression of inflammatory proteins. CONCLUSIONS: These results for the first time demonstrate that the plant sterol guggulsterone suppresses ocular inflammation in EIU, suggesting that the supplementation of guggulsterone could be a novel approach for the treatment of ocular inflammation.


Assuntos
Antineoplásicos/uso terapêutico , Antioxidantes/uso terapêutico , Commiphora , Modelos Animais de Doenças , Lipopolissacarídeos , Pregnenodionas/uso terapêutico , Uveíte/prevenção & controle , Animais , Humor Aquoso/citologia , Humor Aquoso/metabolismo , Western Blotting , Células Cultivadas , Corpo Ciliar/efeitos dos fármacos , Citocinas/metabolismo , Dinoprostona/metabolismo , Ensaio de Imunoadsorção Enzimática , Escherichia coli , Humanos , Proteínas I-kappa B/metabolismo , Injeções Intraperitoneais , Masculino , Metaloproteinase 2 da Matriz/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Endogâmicos Lew , Uveíte/induzido quimicamente , Uveíte/metabolismo
7.
Nat Prod Res ; 21(7): 663-8, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17613825

RESUMO

The reversed-phase HPLC analysis of a methanol extract of the aerial parts of Cuscuta reflexa afforded a non-separable mixture (55 : 45) of two novel tetrahydrofuran derivatives, named swarnalin (1) and cis-swarnalin (2), and a known coumarin, 5,6,7-trimethoxycoumarin (3). The structures of the compounds were elucidated unequivocally by UV, HRFABMS and a series of 1D and 2D NMR analyses. The mixture of 1 and 2 showed significant free radical scavenging activity in the DPPH assay and the RC50 value was found to be 3.80 x 10(-4) mg mL(-1) for the mixture, compared to 2.88 x 10(-5) mg mL(-1) for the positive control, quercetin.


Assuntos
Cuscuta/química , Sequestradores de Radicais Livres/isolamento & purificação , Furanos/isolamento & purificação , Compostos de Bifenilo/química , Sequestradores de Radicais Livres/química , Furanos/química , Hidrazinas/química , Ressonância Magnética Nuclear Biomolecular , Picratos , Componentes Aéreos da Planta/química , Plantas Medicinais/química , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta
8.
Rev. bras. farmacogn ; 17(2): 155-159, abr.-jun. 2007. tab, ilus
Artigo em Inglês | LILACS | ID: lil-456982

RESUMO

The antioxidant activity, general toxicity and cytotoxicity of the methanol extracts of Centaurea urvillei subs. armata and C. mucronifera have been assessed, respectively, by the DPPH assay, the brine shrimp lethality and the MTT cytotoxicity assays. The reversed-phase HPLC analysis of the methanol extracts afforded two bioactive dibenzylbutyrolactone-type lignans, matairesinoside (1) and arctiin (2). The structures of these lignans were elucidated by comprehensive spectroscopic analyses as well as by the direct comparison of experimental data with respective literature data.


A atividade antioxidante, a toxicidade geral e a citotoxidade dos extratos metanólicos de Centaurea urvillei subs. armata e C. mucronifera foram analisados, respectivamente, pelo ensaio DPPH e pelos ensaios de letalidade de Artemia salina e de citotoxidade MTT. A análise dos extratos metanólicos em CLAE de fase reversa apresentou duas lignanas biotivas do tipo dibenzilbutirolactona, matairesinosídeo (1) e arctiina (2). As estruturas destas lignanas foram elucidadas através de análises espectroscópicas completas bem como por comparação direta dos dados experimentais com os respectivos dados da literatura.


Assuntos
Artemia , Asteraceae , Centaurea , Extratos Vegetais/toxicidade , Lignanas
9.
Phytother Res ; 21(8): 757-61, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17450509

RESUMO

Xylocarpus granatum J. König (Meliaceae), commonly known as 'dhundul', is a Bangladeshi mangrove tree, and well distributed in a number of other countries of south-east Asia, Australia and east Africa. Traditionally, X. granatum has been used as an astringent and febrifuge, and also for the treatment of fever, malaria, thrush, cholera, dysentery and diarrhoea in many countries including Bangladesh. Two limonoids, gedunin and 1alpha-hydroxy-1,2-dihydrogedunin, the latter being new, have been isolated from the bark of Xylocarpus granatum by reversed-phase preparative HPLC, and the structures were confirmed by spectroscopic means. The cytotoxic potential of gedunin has been evaluated by the Promega's CellTiter 96 non-radioactive cell proliferation assay using the CaCo-2 colon cancer cell line (IC(50) = 16.83 microM). A summary of the biological activities of gedunin reported to date is also presented.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias do Colo/patologia , Limoninas/química , Limoninas/farmacologia , Meliaceae/química , Antineoplásicos Fitogênicos/química , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Humanos , Estrutura Molecular
10.
J Nat Prod ; 67(9): 1584-7, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15387666

RESUMO

Reversed-phase preparative HPLC of a methanol extract of the rhizomes of Eremostachys glabra yielded three new iridoid glycosides, namely, 6,9-epi-8-O-acetylshanziside methyl ester, 5,9-epi-penstemoside, and 5,9-epi-7,8-didehydropenstemoside. Their structures were elucidated on the basis of spectroscopic data interpretation. The free-radical scavenging activity of these compounds was assessed using the DPPH assay.


Assuntos
Sequestradores de Radicais Livres/isolamento & purificação , Glicosídeos/isolamento & purificação , Iridoides/isolamento & purificação , Lamiaceae/química , Plantas Medicinais/química , Cromatografia Líquida de Alta Pressão , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Irã (Geográfico) , Glicosídeos Iridoides , Iridoides/química , Iridoides/farmacologia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Rizoma/química
11.
Acta Pharm ; 54(4): 277-85, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15634612

RESUMO

A total of six coumarins, bergapten (1), xanthotoxin (2), imperatorin (3), isoimperatorin (4), phellopterin (5) and archangelicin (6), have been isolated from an n-hexane extract of the seeds of Angelica archangelica. The results of comprehensive 2D NMR analyses of archangelicin are discussed.


Assuntos
Angelica archangelica/química , Cumarínicos/análise , Furocumarinas/análise , Metoxaleno/análogos & derivados , Ressonância Magnética Nuclear Biomolecular , Proteínas de Plantas/análise , Plantas Medicinais/química , Sementes/química , 5-Metoxipsoraleno , Metoxaleno/análise , Conformação Proteica , Dobramento de Proteína
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