Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.943
Filtrar
2.
J Sci Food Agric ; 100(2): 614-622, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31597198

RESUMO

BACKGROUND: Lonicera japonica Thunb is a common herb in East Asia. The flower buds are usually regarded as the traditional medicinal part, while leaves and stems are considered less valuable and receive little attention. This study compared the chemical constituents and anti-inflammatory effects of the different tissues in L. japonica Thunb for the first time. RESULTS: Thirty compounds were identified by ultra-performance liquid chromatography-photodiode detector-quadrupole / time of flight-mass spectrometry (UPLC-PDA-Q/TOF-MS/MS) analysis. Hydroxycinnamic acids, flavonoids, and iridoids were identified as the major components. The flower buds (FLJ), leaves (LLJ), and stems (SLJ) of L. japonica Thunb showed strong similarities in chemical components. The LLJ contained higher levels of hydroxycinnamic acids and flavonoids than the FLJ and SLJ. Furthermore, FLJ, LLJ, and SLJ exhibited potent anti-inflammatory activity in croton oil-induced ear edema and carrageenan-induced paw edema assays in mice. Moreover, FLJ, LLJ, and SLJ showed a cytoprotective effect on lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. Lipopolysaccharide-induced increases in nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were suppressed by treatments of FLJ, LLJ, and SLJ, respectively. The LLJ possessed a stronger anti-inflammatory effect than the FLJ. CONCLUSION: Leaves and stems of L. japonica Thunb have chemical components and anti-inflammatory properties similar to flower buds, and may become alternative or supplementary sources of flower buds. © 2019 Society of Chemical Industry.


Assuntos
Anti-Inflamatórios/química , Edema/tratamento farmacológico , Lonicera/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Animais , Anti-Inflamatórios/administração & dosagem , Carragenina/efeitos adversos , Cromatografia Líquida de Alta Pressão , Edema/induzido quimicamente , Edema/genética , Edema/imunologia , Flavonoides/administração & dosagem , Flavonoides/química , Flores/química , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Camundongos , Folhas de Planta/química , Caules de Planta/química , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
3.
Eur J Pharm Sci ; 140: 105101, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31639436

RESUMO

Gastric irritation and ulcerogenic effect of the acidic NSAIDs are of the most challenging problems in designing novel anti-inflammatory agents. In this study, the new prodrugs were prepared through Steglich esterification reaction between the carboxylic acid functional group of etodolac or tolfenamic acid and thymol. The structures were confirmed by IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analysis. Their chemical stability in addition to a kinetic study of their hydrolysis in 20% liver homogenate and 10% buffered plasma were investigated. In vitro enzymatic hydrolysis showed half-life times 88.84 and 106.61 min for the prodrugs of etodolac and tolfenamic acid, respectively. Their ability to inhibit paw edema and their ulcerogenic potential were assessed in rats and compared to their parent drugs. the prodrugs were found to be stable in different pHs at room and body temperatures. Both prodrugs proved to possess high percentage of inhibition of paw edema (94.68 & 97.1%) in rats comparable to that of the parent drugs (90.33 & 93.23%) and, most importantly with lower ulcerogenic potential. The prodrugs are expected to be converted to their parent drugs rapidly in plasma and liver in vivo and proved to be safer than their parent drugs. The study opens a perspective chance that can be a backbone for further investigations.


Assuntos
Anti-Inflamatórios/síntese química , Edema/tratamento farmacológico , Etodolac/síntese química , Pró-Fármacos/síntese química , Úlcera Gástrica/induzido quimicamente , ortoaminobenzoatos/síntese química , Animais , Anti-Inflamatórios/farmacologia , Desenho de Drogas , Estabilidade de Medicamentos , Etodolac/farmacologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Cinética , Fígado/metabolismo , Masculino , Estrutura Molecular , Plasma/metabolismo , Pró-Fármacos/farmacologia , Ratos , Ratos Wistar , Úlcera Gástrica/prevenção & controle , Relação Estrutura-Atividade , Temperatura Ambiente , ortoaminobenzoatos/farmacologia
4.
Medicine (Baltimore) ; 98(41): e17551, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593137

RESUMO

RATIONALE: Refractory edema is characterized by persistent swelling which does not react to diuretic use and sodium restriction. Traditional herbal medicine, Gwack Rhyung Tang and Chunggan extract effectively treated refractory lower limb edema caused by cirrhosis and improved liver function. PATIENT CONCERNS: A 64-year-old male patient with a history of hypertension, diabetes mellitus, hepatic encephalopathy, and cellulitis presented lower limb edema which did not react to diuretics for more than 7 months. DIAGNOSES: Refractory edema caused by cirrhosis. INTERVENTIONS: The patient was treated for 25 days using Gwack Rhyung Tang and Chunggan extract. OUTCOMES: Loss of body weight, decrease in circumferences of both lower limb and improvement of liver function biochemistry results are checked. There was no recurrence or aggravation of the condition up to 3 weeks of follow-up periods. LESSONS: Traditional herbal medicine can be an effective alternative for refractory edema due to cirrhosis with improving liver function.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Edema/tratamento farmacológico , Medicina Tradicional/métodos , Diuréticos/uso terapêutico , Resistência a Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Fibrose/complicações , Medicina Herbária , Humanos , Extremidade Inferior/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
5.
Planta Med ; 85(16): 1216-1224, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31546267

RESUMO

Bixin is the main natural apocarotenoid extracted from the seeds of Bixa orellana, widely used as a cosmetic and textile colorant. Despite the description of several pharmacological properties of B. orellana extracts, little has been studied regarding the pharmacological properties of bixin. Then we aimed to investigate the potential anti-inflammatory and antinociceptive effect of bixin in preclinical models of inflammation and acute pain. The anti-inflammatory activity of bixin (15 or 30 mg/kg, orally) was determined using carrageenan-induced paw edema and the myeloperoxidase (MPO) activity in male Wistar rats. The antinociceptive effect of bixin was assessed in the formalin and hot plate tests in rats (at same doses) and in the acetic acid-induced writhing test in Swiss albino male mice (at doses of 27 or 53 mg/kg). General locomotor activity was evaluated in the open field test. Only the higher dose of bixin significantly decreased the carrageenan-induced paw edema and the MPO activity and increased the latency time in the hot plate. Both doses of bixin significantly reduced the number of flinches in both phases of the formalin test and the number of acetic acid-induced writhings without changing the locomotor performance in the open field test. This study validates the use of bixin as an anti-inflammatory trough mechanism related to the reduction of neutrophil migration. Furthermore, this is the first report showing the antinociceptive property of bixin, which does not appear to be related to the sedative effect. Further studies are necessary to characterize the mechanisms involved in these effects.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Bixaceae/química , Carotenoides/farmacologia , Edema/tratamento farmacológico , Ácido Acético/efeitos adversos , Analgésicos/química , Animais , Anti-Inflamatórios/química , Carotenoides/química , Carragenina/efeitos adversos , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Masculino , Camundongos , Medição da Dor , Ratos , Ratos Wistar
6.
BMC Complement Altern Med ; 19(1): 263, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547823

RESUMO

BACKGROUND: Inflammation is a symptom associated with many diseases. This symptom is treated with steroidal and non-steroidal anti-inflammatory drugs, which can cause severe side effects when used as long-term treatments. Natural products are an alternative source of new compounds with anti-inflammatory activity. Jefea gnaphalioides (Astereaceae) (A. Gray) is a plant species used to treat inflammatory problems, in Mexico. This study determined the anti-inflammatory activity and the composition of the methanol extract of Jefea gnaphalioides (MEJG). METHODS: The extract was obtained by heating the plant in methanol at boiling point for 4 h, and then the solvent was evaporated under vacuum (MEJG). The derivatization of the extract was performed using Bis-(trimethylsilyl) trifluoroacetamide, and the composition was determined by GC-MS. Total Phenols and flavonoids were determined by Folin-Ciocalteu AlCl3 reaction respectively. The antioxidant activity of MEJG was determined by DPPH method. The acute and chronic anti-inflammatory effects were evaluated on a mouse ear edema induced with 12-O-Tetradecanoylphorbol-13-acetate (TPA). Acute oral toxicity was tested in mice at doses of MEJG of 5000, 2500 and 1250 mg/kg. The levels of NO, TNF-α, IL-1ß and IL-6 were determinate in J774A.1 macrophages stimulated by Lipopolysaccharide. The production of inflammatory interleukins was measured using commercial kits, and nitric oxide was measured by the Griess reaction. RESULTS: The anti-inflammatory activity of MEJG in acute TPA-induced ear edema was 80.7 ± 2.8%. This result was similar to the value obtained with indomethacin (IND) at the same dose (74.3 ± 2.8%). In chronic TPA-induced edema at doses of 200 mg/kg, the inhibition was 45.7%, which was similar to that obtained with IND (47.4%). MEJG have not toxic effects even at a dose of 5000 mg/kg. MEJG at 25, 50, 100 and 200 µg/mL decreased NO, TNF-α, IL-1ß and IL-6 production in macrophages stimulated with LPS. The major compounds in MEJG were α-D-Glucopyranose (6.71%), Palmitic acid (5.59%), D-(+)-Trehalose (11.91%), Quininic acid (4.29%) and Aucubin (1.17%). Total phenolic content was 57.01 mg GAE/g and total flavonoid content was 35.26 mg QE/g MEJG had antioxidant activity. CONCLUSIONS: MEJG has anti-inflammatory activity.


Assuntos
Anti-Inflamatórios/administração & dosagem , Asteraceae/química , Edema/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Edema/genética , Edema/imunologia , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
7.
J Med Food ; 22(10): 1078-1086, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31549890

RESUMO

This study evaluated to determine the phenolic and flavonoids contents, and antioxidant, anti-inflammatory, and antiproliferative activity of the hydromethanolic extracts of the leaves, pulp, and seeds of Annona cacans. The isolation and structural identification of the constituent acetogenin, phenolic acid, and flavonoids were also reported. Antioxidant capacity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH), ethylbenzothiazoline-6-sulfonic acid (ABTS), and ß-carotene/linoleic acid methods. Cell proliferation was determined by spectrophotometric quantification of the cellular protein content using a sulforhodamine B assay. Anti-inflammatory activity was evaluated in paw edema model, to myeloperoxidase (MPO) activity induced by carrageenan in mice. Fractionation resulted in the isolation of one acetogenin (annoreticuin-9-one), two flavonoids (quercetin-3-O-ß-glucoside-6-O-α-rhamnoside and kaempferol-3-O-ß-glucoside), and one phenolic acid (p-coumaric acid). The pulp extract presented potent antioxidant activities by the DPPH (IC50 = 44.08 µg/mL) and ABTS (IC50 = 39.32 µg/mL) methods, as well as high contents of phenols (618.95 mg GA/g) and flavonoids (477.35 mg QE/g). The bioguided fractionation demonstrated that the ethyl acetate fraction of the pulp extract and annoreticuin-9-one showed potent antiproliferative activity against ovarian cancer (GI50 = 6.4 µg/mL). The anti-inflammatory activity demonstrated significant inhibition of edema compared to the control group in 2 and 4 h; in addition, the extracts inhibited the increase in MPO activity after 6 h, when compared to the DEX and control groups. For the first time, this study demonstrated antioxidant, anti-inflammatory, and antiproliferative activity, as well as compounds isolated, suggesting that A. cacans could also be potential sources for prevention of cancer and other diseases associated with oxidative stress.


Assuntos
Annona/química , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Acetogeninas/isolamento & purificação , Animais , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/isolamento & purificação , Carragenina , Linhagem Celular Tumoral , Edema/induzido quimicamente , Edema/tratamento farmacológico , Flavonoides/isolamento & purificação , Humanos , Hidroxibenzoatos/isolamento & purificação , Masculino , Camundongos , Estrutura Molecular , Peroxidase/metabolismo , Fenóis/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Sementes/química
8.
BMC Complement Altern Med ; 19(1): 214, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412852

RESUMO

BACKGROUND: The present study evaluated the antinociceptive effect of the bark of Artocarpus lacucha, which is used for the treatment of stomachache, headache and boils in the traditional system of medicine. METHODS: The antinociceptive activity was investigated by the tail immersion, hot plate, acetic acid- & formalin-induced nociception and carrageenan-induced paw edema tests using a hydro-methanolic extract of A. lacucha bark. The plant extract was found to contain a substantial amount of phenolic compounds according to the total phenolic and flavonoid content assay. A phenolic metabolite, (+)-catechin, has been isolated using different chromatographic techniques. The compound was characterized with 1D and 2D NMR spectroscopic data. (+)-catechin, isolated from A. lacucha was assessed for antinociceptive effects swiss albino mice. Furthermore, the possible involvement of opioid receptors and ATP-sensitive K+ channel for the effect of the plant extract and (+)-catechin has been justified using naloxone and glibenclamide, respectively. RESULTS: Oral administration (p.o) of the plant extract (50-200 mg/Kg b.w.) resulted in significant thermal pain protection in the hot plate and tail immersion tests. The action of the plant extract was significantly antagonized by naloxone, a non-selective opioid antagonist, in the hot plate and tail immersion tests, which supports the involvement of opioid receptors. Both the plant extract and (+)-catechin, (50-200 mg/Kg b.w., p.o.) significantly diminished the acetic acid- & formalin-induced nociception, and carrageenan-induced paw edema. Glibenclamide, an ATP-sensitive K+ channel blocker, significantly reversed their effect in the acetic acid-induced writhing test which indicates the participation of ATP-sensitive K+ channel system. CONCLUSIONS: The investigation revealed potential central and peripheral antinociceptive effects of A. lacucha bark supports its applications in the traditional system of medicine.


Assuntos
Analgésicos/administração & dosagem , Artocarpus/química , Catequina/administração & dosagem , Edema/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Analgésicos/química , Analgésicos/isolamento & purificação , Animais , Carragenina/efeitos adversos , Catequina/análise , Catequina/isolamento & purificação , Edema/induzido quimicamente , Humanos , Masculino , Camundongos , Nociceptividade/efeitos dos fármacos , Dor/tratamento farmacológico , Extratos Vegetais/química
9.
Int J Mol Sci ; 20(16)2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31404946

RESUMO

Heart failure (HF) patients frequently have elevated plasma renin activity. We examined the significance of elevated plasma renin activity in a translationally-relevant model of dilated cardiomyopathy (DCM), which replicates the progressive stages (A-D) of human HF. Female mice with DCM and elevated plasma renin activity concentrations were treated with a direct renin inhibitor (aliskiren) in a randomized, blinded fashion beginning at Stage B HF. By comparison to controls, aliskiren treatment normalized pathologically elevated plasma renin activity (p < 0.001) and neprilysin levels (p < 0.001), but did not significantly alter pathological changes in plasma aldosterone, angiotensin II, atrial natriuretic peptide, or corin levels. Aliskiren improved cardiac systolic function (ejection fraction, p < 0.05; cardiac output, p < 0.01) and significantly reduced the longitudinal development of edema (extracellular water, p < 0.0001), retarding the transition from Stage B to Stage C HF. The normalization of elevated plasma renin activity reduced the loss of body fat and lean mass (cachexia/sarcopenia), p < 0.001) and prolonged survival (p < 0.05). In summary, the normalization of plasma renin activity retards the progression of experimental HF by improving cardiac systolic function, reducing the development of systemic edema, cachexia/sarcopenia, and mortality. These data suggest that targeting pathologically elevated plasma renin activity may be beneficial in appropriately selected HF patients.


Assuntos
Amidas/uso terapêutico , Cardiomiopatia Dilatada/tratamento farmacológico , Fumaratos/uso terapêutico , Renina/antagonistas & inibidores , Renina/sangue , Animais , Caquexia/sangue , Caquexia/complicações , Caquexia/tratamento farmacológico , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/complicações , Modelos Animais de Doenças , Edema/sangue , Edema/complicações , Edema/tratamento farmacológico , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Camundongos , Camundongos Endogâmicos C57BL
10.
Int J Nanomedicine ; 14: 6135-6150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447556

RESUMO

Background: Nanostructured lipid carriers (NLCs) are emerging as attractive drug carriers in transdermal drug delivery. The surface modification of NLCs with cell-penetrating peptides (CPPs) can enhance the skin permeation of drugs. Purpose: The objective of the current study was to evaluate the ability of the cell-penetrating peptide (CPP) polyarginine to translocate NLCs loaded with lornoxicam (LN) into the skin layers and to evaluate its anti-inflammatory effect. Methods: The NLCs were prepared using an emulsion evaporation and low temperature solidification technique using glyceryl monostearates, triglycerides, DOGS-NTA-Ni lipids and surfactants, and then six histidine-tagged polyarginine containing 11 arginine (R11) peptides was modified on the surface of NLCs. Results: The developed NLCs formulated with LN and R11 (LN-NLC-R11) were incorporated into 2% HPMC gels. NLCs were prepared with a particle size of (121.81±3.61)-(145.72±4.78) nm, and the zeta potential decreased from (-30.30±2.07) to (-14.66±0.74) mV after the modification of R11 peptides. The encapsulation efficiency and drug loading were (74.61±1.13) % and (7.92±0.33) %, respectively, regardless of the surface modification. Cellular uptake assays using HaCaT cells suggested that the NLC modified with R11 (0.02%, w/w) significantly enhanced the cell internalization of nanoparticles relative to unmodified NLCs (P<0.05 or P<0.01). An in vitro skin permeation study showed better permeation-enhancing ability of R11 (0.02%, w/w) than that of other content (0.01% or 0.04%). In carrageenan-induced rat paw edema models, LN-NLC-R11 gels inhibited rat paw edema and the production of inflammatory cytokines compared with LN-NLC gels and LN gels (P<0.01). Conclusion: In our investigation, it was strongly demonstrated that the surface modification of NLC with R11 enhanced the translocation of LN across the skin, thereby alleviating inflammation.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Edema/tratamento farmacológico , Lipídeos/química , Nanoestruturas/química , Peptídeos/farmacologia , Piroxicam/análogos & derivados , Administração Cutânea , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Carragenina , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Peptídeos Penetradores de Células/farmacologia , Edema/induzido quimicamente , Edema/metabolismo , Emulsões/química , Endocitose/efeitos dos fármacos , Géis/química , Humanos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/ultraestrutura , Oligopeptídeos/farmacologia , Oligopeptídeos/uso terapêutico , Piroxicam/administração & dosagem , Piroxicam/farmacologia , Piroxicam/uso terapêutico , Coelhos , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Absorção Cutânea/efeitos dos fármacos , Testes de Irritação da Pele
11.
Chem Biol Interact ; 311: 108790, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31400342

RESUMO

Preclinical assays play a key role in research in research on the neurobiology of pain and the development of novel analgesics. Drugs available for the treatment of inflammatory pain are not fully effective and show adverse effects. Thus, we investigated the antinociceptive, anti-inflammatory and anti-hyperalgesic effects of bis(3-amino-2-pyridine) diselenide (BAPD), a new analgesic drug prototype. BAPD effects were investigated using nociception models induced by chemical (glutamate), immunologic (Freund's Complete Adjuvant - CFA) and thermal stimuli in Swiss mice. Mice were orally (p.o.) treated with BAPD (0.1-50 mg/kg) 30 min prior to the glutamate and hot-plate tests and a time-course (0.5 up to 8 h) of the antinociceptive effect of BAPD (50 mg/kg, p. o.) was evaluated in a CFA model. In the CFA model, BAPD effects on cyclooxygenase-2 (COX-2), tumor necrosis factor (TNFα) and interferon-γ (INF-γ) expression, myeloperoxidase (MPO) activity, oxidative (2,2'-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels) and histological parameters were evaluated. The safety of the compound (50 and 300 mg/kg, p. o.) was verified for 72 h. BAPD reduced the licking time induced by glutamate and caused an increase in latency response to thermal stimulus. Naloxone reversed the antinociceptive effect of BAPD. Paw edema formation induced by glutamate or CFA injection was reduced by BAPD. Mechanical hyperalgesia induced by CFA was attenuated by BAPD. BAPD did not protect against the increase in MPO activity and decrease of the 2,2'-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels induced by CFA. BAPD protected against histological alterations and reduction on the levels of gene expression COX-2 and INF-γ in the paw of mice exposed to CFA. BAPD was safe at the doses and time evaluated. BAPD exerts acute antinociceptive, anti-inflammatory and anti-hyperalgesic actions, suggesting that it may represent an alternative in the future development of new therapeutic strategies.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/metabolismo , Interferon gama/metabolismo , Nociceptividade/efeitos dos fármacos , Receptores Opioides/metabolismo , Analgésicos/química , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Ciclo-Oxigenase 2/genética , Edema/tratamento farmacológico , Edema/patologia , Comportamento Exploratório/efeitos dos fármacos , Pé/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Interferon gama/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Dor/tratamento farmacológico , Dor/patologia , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores Opioides/genética , Testes de Toxicidade Aguda , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
12.
Eur J Med Chem ; 182: 111601, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31445233

RESUMO

The cyclic enaminone moiety has been identified as a new scaffold for selective inhibition of cyclooxygenase-2 with anti-inflammatory and analgesic activities. The designed cyclic enaminones have been synthesized conveniently through the development of a new catalyst-free methodology and evaluated for cyclooxygenase (COX-1 and COX-2) inhibitory activities. Three compounds 7d, 8, and 9 predominantly inhibited COX-2 with selectivity index of 74.09, 19.45 and 108.68, respectively, and were assessed for in vivo anti-inflammatory activity in carrageenan induced rat paw edema assay. The anti-inflammatory activity of 7d was comparable to that of celecoxib at a dose of 12.5 mg/kg. However, the compounds 8 and 9 were more/equally effective as anti-inflammatory agent compared to celecoxib at the doses of 12.5 mg/kg and 25 mg/kg and also exhibited anti-inflammatory activity comparable to that of diclofenac. The therapeutic potential of the most active compound 9 was further assessed by performing in vivo thermal and mechanical hyperalgesia tests using various models that revealed its analgesic activity. The in vivo non-ulcerogenicity of 9 revealed the gastrointestinal safety as compared to the non-selective COX inhibitor indomethacin. The in vitro antioxidant activity and in vivo experiments on heart rate and blood pressure provided the cardiovascular safety profile of 9. The molecular docking studies rationalize the COX-2 selectivity of the newly found anti-inflammatory compounds 7d, 8, and 9.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Compostos Heterocíclicos/farmacologia , Analgésicos/síntese química , Analgésicos/química , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antioxidantes/síntese química , Antioxidantes/química , Carragenina , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Compostos Heterocíclicos/síntese química , Compostos Heterocíclicos/química , Humanos , Masculino , Simulação de Acoplamento Molecular , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade
13.
Chem Pharm Bull (Tokyo) ; 67(8): 786-794, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366828

RESUMO

Teriflunomide (TEF, A771726) is the active metabolite of leflunomide (LEF), a disease-modifying anti-rheumatic drug. The main purpose of this study was to develop and evaluate water-in-oil (W/O) microemulsion formulation of TEF. The W/O microemulsion was optimized formula is the physical and chemical stability of lecithin, ethanol, isopropyl myristate (IPM) and water (20.65/20.78/41.52/17.05 w/w) by using the pseudo-ternary phase diagram and the average droplet size is about 40 nm. The permeability of TEF microemulsion is about 6 times higher than control group in vitro penetration test. The results of anti-inflammatory effect showed that compared with the control group, the external TEF microemulsion group could significantly inhibit swelling of paw in rats, and no significant difference compared with oral LEF group. The results of hepatotoxicity test show that there were normal content of alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and no obvious inflammatory infiltration of TEF microemulsion group compared with LEF group. The plasma concentration curve showed that compared with LEF group, the peak concentration of TEF microemulsion group was decreased, the half-life (t1/2) was prolonged, and the relative bioavailability of TEF microemulsion was 75.35%. These results suggest that TEF W/O microemulsion can be used as a promising preparation to play an anti-inflammatory role while significantly reducing hepatotoxicity.


Assuntos
Antirreumáticos/farmacologia , Crotonatos/farmacologia , Sistemas de Liberação de Medicamentos , Edema/tratamento farmacológico , Toluidinas/farmacologia , Animais , Antirreumáticos/química , Crotonatos/química , Composição de Medicamentos , Edema/patologia , Emulsões/síntese química , Emulsões/química , Estrutura Molecular , Óleos/química , Medição da Dor , Ratos , Ratos Sprague-Dawley , Toluidinas/química , Água/química
14.
Cell Biochem Funct ; 37(7): 474-485, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31365139

RESUMO

The effect of quercetin was assessed in rats induced with complete Freund adjuvant (CFA). Arthritis scores, paw oedema, latency, activities of myeloperoxidase (MPO), ectonucleoside triphosphate diphosphohydrolase (E-NTPDase), and ectoadenosine deaminase (E-ADA) in lymphocytes were determined. Furthermore, nucleotide and nucleoside levels as well as the secretion of pro- and anti-inflammatory cytokines were evaluated. Animals were treated with saline and quercetin in doses of 5, 25, and 50 mg/kg for 45 days. The result revealed that quercetin (50 mg/kg) reduced arthritis score and paw oedema, and increased the latency in the thermal hyperalgesia test. Histopathological analysis showed that all the doses of quercetin reduced infiltration of inflammatory cells. MPO activity was increased in the arthritis group; however, quercetin reduced this activity. E-NTPDase activity was increased in lymphocytes of arthritis rats, and treatment with quercetin reversed this increase. However, E-ADA activity was reduced in the arthritis group, and treatment with quercetin modulated the activity of this enzyme in arthritis rat groups. Serum adenosine levels were increased in arthritis, and the levels were lowered with quercetin treatment. Quercetin treatment in arthritis groups decreased the elevated levels of cytokines in the arthritis control group. Thus, quercetin demonstrated an anti-inflammatory effect, and this flavonoid may be a promising natural compound for the treatment of arthritis. SIGNIFICANCE OF THE STUDY: Quercetin may represent a potential therapeutic compound in the treatment of rheumatoid arthritis. Findings from this study indicate that quercetin suppresses swelling and attenuates the underlying inflammatory responses. This is the first report where quercetin was shown to modulate the immune response to arthritis via attenuation of the purinergic system (E-NTPDase and E-ADA activities) and the levels of IFN-gamma and IL-4. Thus, this work is relevant to basic research and may be translated into clinical practice.


Assuntos
AMP Desaminase/antagonistas & inibidores , Adenosina Trifosfatases/antagonistas & inibidores , Anti-Inflamatórios não Esteroides/farmacologia , Artrite Reumatoide/tratamento farmacológico , Citocinas/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Quercetina/farmacologia , AMP Desaminase/metabolismo , Adenosina Trifosfatases/metabolismo , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/metabolismo , Citocinas/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Feminino , Adjuvante de Freund , Ratos , Ratos Wistar
16.
Molecules ; 24(14)2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31323775

RESUMO

Curcumin, derived from the rhizome Curcuma longa, has been scientifically proven to possess anti-inflammatory activity but is of limited clinical and veterinary use owing to its low bioavailability and poor solubility. Hence, analogs of curcuminoids with improved biological properties have been synthesized to overcome these limitations. This study aims to provide the pharmacological basis for the use of 5-(3,4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (DHHPD), a synthetic curcuminoid analog, as an anti-edematogenic and anti-granuloma agent. The carrageenan-induced paw edema and the cotton pellet-induced granuloma assays were used to assess the anti-inflammatory activity of DHHPD in mice. The effects of DHHPD on the histaminergic, serotonergic, and bradykininergic systems were determined by the histamine-, serotonin-, and bradykinin-induced paw edema tests, respectively. DHHPD (0.1, 0.3, 1, and 3 mg/kg, intraperitoneal) evoked significant reductions (p < 0.05) in carrageenan-induced paw edema at different time intervals and granuloma formation (p < 0.0001) by 22.08, 32.57, 37.20, and 49.25%, respectively. Furthermore, DHHPD significantly reduced paw edema (p < 0.05) induced by histamine, serotonin, and bradykinin. The present study suggests that DHHPD exerts anti-edematogenic activity, possibly by inhibiting the synthesis or release of autacoid mediators of inflammation through the histaminergic, serotonergic, and bradykininergic systems. The anti-granuloma effect may be attributed to the suppression of transudative, exudative, and proliferative activities associated with inflammation.


Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Diarileptanoides/química , Diarileptanoides/farmacologia , Animais , Anti-Inflamatórios/síntese química , Diarileptanoides/síntese química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/tratamento farmacológico , Edema/etiologia , Granuloma/tratamento farmacológico , Granuloma/etiologia , Masculino , Camundongos , Estrutura Molecular , Testes de Toxicidade Aguda
17.
Complement Ther Med ; 45: 254-261, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31331571

RESUMO

PURPOSE: The objective of the present study was to evaluate the systemic anti-inflammatory activity of the hydroalcoholic extract of the leaves of Licania rigida Benth (EHFLR) on models of systemic inflammation in mice. METHODS: The quantitative chemical profiles of phenolic acids and flavonoids were performed by High-Performance Liquid Chromatography (HPLC). Systemic anti-inflammatory activity was determined from carrageenan and dextran-induced paw edema models and the animals were orally treated (p.o.) with EHFLR at doses of 25, 50, 100 mg/kg, indomethacin (10 mg/kg) for carrageenan-induced paw edema and promethazine (6 mg/kg) for dextran-induced paw edema. The possible mechanisms involved in the anti-inflammatory action of the extract were evaluated by the paw edema models induced by histamine and arachidonic acid, and by the model of carrageenan-induced peritonitis, where vascular permeability and leukocyte migration to the peritoneal cavity were evaluated. RESULTS: The results of the HPLC identified the presence of phenolic acids and flavonoids, with chlorogenic acid (1.16%) and Caempferol (0.81%) as the main constituents. From the results, it was concluded that the extract has an LD50 ≥5000 mg/kg when administered orally in mice as this dose did not trigger deaths in any of the observed groups. EHFLR (25 mg/kg) showed a significant antiderematogenic effect on histamine and arachidonic acid-induced paw edema at the third hour of the tests, with a percentage of inhibition of 46.64% and 18.33%, respectively. The extract (25 mg/kg, p.o.) also significantly reduced vascular permeability and leukocyte migration in the peritoneal cavity. CONCLUSIONS: It is concluded that EHFLR exerts a systemic anti-inflammatory action, which seems to depend, at least in part, on the inhibition of arachidonic acid metabolism and the action of vasoactive amines. In addition, the extract reduced the leukocyte migration in the peritoneal cavity, indicating that its action may be linked to the inhibition of pro-inflammatory cytokines.


Assuntos
Anti-Inflamatórios/farmacologia , Chrysobalanaceae/química , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Carragenina/farmacologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Flavonoides/farmacologia , Hidroxibenzoatos/farmacologia , Masculino , Camundongos , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Fitoterapia/métodos , Folhas de Planta/química
18.
Mater Sci Eng C Mater Biol Appl ; 103: 109742, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349429

RESUMO

This study aimed to develop nanocapsules containing ketoprofen using rose hip oil (Keto-NC) as oil core, and to evaluate their anti-inflammatory activity in acute and chronic ear edema models in mice. Physicochemical characterization, drug release, photostability and cytotoxicity assays were performed for the developed Keto-NC formulations and compared to ketoprofen-loaded nanocapsules using medium chain triglycerides as oil core (Keto-MCT-NC). Anti-inflammatory activity of orally delivered KP (Ketoprofen-free; 10 mg.kg-1) or Keto-NC (2.5; 5; 10 mg.kg-1) was assessed in mouse acute and chronic ear edema induced by croton oil (CO). Edema histological characteristics were determined by H&E stain, and redox parameters were analyzed in blood plasma and erythrocytes. Keto-MCT-NC and Keto-NC did not exhibit differences regarding physicochemical parameters, including size diameters, polydispersity index, pH, Ketoprofen content, and encapsulation efficiency. However, Keto-NC, which contains rose hip oil as lipid core, decreased drug photodegradation under UVC radiation when compared to Keto-MCT-NC. KP or Keto-NC were not cytotoxic to keratinocyte cultures and produced equal edema inhibition in the acute protocol. Conversely, in the chronic protocol, Keto-NC was more effective in reducing edema (~60-70% on 7-9th days of treatment) when compared to KP (~40% on 8-9th days of treatment). This result was confirmed by histological analysis, which indicated reduction of edema and inflammatory infiltrate. A sub-therapeutic dose of Keto-NC (5 mg.kg-1) significantly reduced edema when compared to control. Finally, KP and Keto-NC exhibited similar effects on redox parameters, suggesting that the advantages associated with Ketoprofen nanoencapsulation did not involve oxidative stress pathways. The results showed that Keto-NC was more efficient than KP in reducing chronic inflammation. These data may be important for the development of strategies aiming treatment of chronic inflammatory diseases with fewer adverse effects.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Inflamação/tratamento farmacológico , Cetoprofeno/farmacologia , Nanocápsulas/química , Óleos Vegetais/química , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacocinética , Linhagem Celular , Doença Crônica , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Edema/tratamento farmacológico , Humanos , Queratinócitos/efeitos dos fármacos , Cetoprofeno/administração & dosagem , Cetoprofeno/farmacocinética , Masculino , Camundongos Endogâmicos C57BL , Nanocápsulas/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Rosa/química
19.
J Agric Food Chem ; 67(32): 8810-8818, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31318199

RESUMO

Citrus grandis (L.) Osbeck is a popular fruit cultivated around the world, and its peels are sometimes used for the treatment of cough, abdominal pain, and indigestion in China. However, the peel is discarded after fruit consumption in most cases, and its chemical constituents and biological activities have not been validated before. The present study focused on evaluation of the chemical and pharmacological profile of coumarins from peels of C. grandis against inflammation. The extracts and phytochemicals from peels of C. grandis were prepared, and anti-inflammatory activities were carried out in vivo and in vitro, including inhibiting xylene-induced ear edema and carrageenan-induced paw edema in mice and the production of inflammatory cytokines (interleukin 1ß, prostaglandin 2, and tumor-necrosis factor α) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results indicated that methanolic extract, ethyl acetate fraction, and four major coumarins (compounds 7, 8, 13, and 16) inhibited swelling induced by xylene and carrageenan, separately, in vivo. Furthermore, 18 coumarins inhibited inflammatory factor secretion in macrophages primed by LPS, in which compounds 4, 6, 7, 10, 17 showed the most pronounced change, which were comparable to dexamethasone. In summary, peel of C. grandis showed an anti-inflammatory effect and coumarin compounds were responsible for regulating inflammatory mediators and cytokines, which might provide a novel nutritional strategy for inflammatory diseases.


Assuntos
Anti-Inflamatórios/administração & dosagem , Citrus/química , Cumarínicos/administração & dosagem , Edema/tratamento farmacológico , Frutas/química , Extratos Vegetais/administração & dosagem , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Cumarínicos/química , Cumarínicos/isolamento & purificação , Dinoprostona/imunologia , Edema/genética , Edema/imunologia , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células RAW 264.7 , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Resíduos/análise
20.
Biomater Sci ; 7(9): 3918-3925, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31322162

RESUMO

Polymer gels can be classified as chemical and physical gels, depending on the type of cross-link. Physical gels usually form by physical cross-linking, such as hydrogen bonding, van der Waals and/or p-p interactions, which can avoid the use of additional cross-linking agents. Polyamidoamine (PAMAM) dendrimers possess abundant active groups on their surfaces. Modified dendrimers have been used as versatile linkers in some projects. In this work, polymer gels composed of PAMAM dendrimers without any covalent bonding cross-linking agents were prepared. The number of amino groups and ester groups on the surface of the dendrimers was precisely regulated to help form hydrogen bonds between adjacent dendrimers. The prepared dendrimer-based polymer gels retain the properties of PAMAM dendrimers such as antibacterial properties, and the unique structures make the gels exhibit high compressive strengths but relatively low tensile strengths. Interestingly, the prepared gels show good anti-inflammatory properties in acute inflammation models of mice with ear edema. The inflammatory inhibition rate and hematoxylin-eosin (H&E) staining method were used to confirm the anti-inflammatory effect. This present study demonstrates that the dendrimer-based polymer gels achieved through hydrogen bonding could be a versatile platform for tissue engineering.


Assuntos
Anti-Inflamatórios/farmacologia , Dendrímeros/química , Poliaminas/química , Células 3T3 , Animais , Sobrevivência Celular/efeitos dos fármacos , Força Compressiva , Dendrímeros/farmacologia , Edema/tratamento farmacológico , Feminino , Géis , Ligações de Hidrogênio , Camundongos , Camundongos Endogâmicos BALB C , Poliaminas/farmacologia , Resistência à Tração
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA