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1.
Nanotechnology ; 31(17): 175102, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31935712

RESUMO

Carbon quantum dots (CDs) have attracted increased attention in recent decades because of their various applications in biosensing, bioimaging and drug delivery. In the present study, we have synthesized bifunctional ibuprofen-based carbon quantum dots (ICDs) using a simple one-step microwave-assisted method, for simultaneous bioimaging and anti-inflammatory effects. The ICDs exhibited high stability, low toxicity, negligible cytotoxicity and good biocompatibility in water. In particular, the produced ICDs demonstrated a decent imaging ability and excellent anti-inflammatory effects in vivo, making them potentially useful in bioimaging and future clinical treatment. Our results demonstrated that ICDs show promise in applications such as multifunctional biomaterials, depending on the selection of carbon sources, which would provide important guidance for the future design of multifunctional CDs in the field of biomedicine.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Carbono/química , Ibuprofeno/administração & dosagem , Inflamação/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Carragenina/efeitos adversos , Modelos Animais de Doenças , Estabilidade de Medicamentos , Células HeLa , Humanos , Ibuprofeno/química , Ibuprofeno/farmacologia , Inflamação/induzido quimicamente , Masculino , Camundongos , Micro-Ondas , Imagem Molecular , Pontos Quânticos/química
2.
Nat Prod Res ; 34(11): 1535-1541, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30507264

RESUMO

Since a long time caffeine has been used in pharmaceutical and cosmetic preparations due to its favorable effects on the skin. The aim of this study was to evaluate the topical anti-inflammatory activity (carrageenan-induced paw oedema) of an ointment prepared using a methanolic extract from green beans of C. robusta via histology. Results showed that the treatment with the ointment reduced the paw oedema within 3 and 5 h post-carrageenan administration. The immunohistochemical evaluations of αSMA, Langerin and S100 gave further support to the morphological analysis. Finally, the methanolic extract from green beans of C. robusta proved to possess elevated free radical scavenger capability by DPPH assay, which may contribute to the observed anti-inflammatory activity.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Café/química , Extratos Vegetais/farmacologia , Pele/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Carragenina/efeitos adversos , Edema/tratamento farmacológico , Depuradores de Radicais Livres/farmacologia , Metanol , Extratos Vegetais/isolamento & purificação , Ratos
3.
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
4.
Molecules ; 24(23)2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31816866

RESUMO

Indandiones are a relatively new group of compounds presenting a wide range of biological activities. The synthesis of these compounds was performed via a Knoevenagel reaction between an aldehyde and 1,3-indandione and were obtained with a yield up to 54%. IR, 1H-Nucleic Magnetic Resonance (NMR), 13C-NMR, LC/MS ESI+ and elemental analysis were used for the confirmation of the structures of the novel derivatives. Lipophilicity values of compounds were calculated theoretically and experimentally by reversed chromatography method as values RM. The novel derivatives were studied through in vitro and in vivo experiments for their activity as anti-inflammatory and antioxidant agents and as inhibitors of lipoxygenase, trypsin, and thrombin. The inhibition of the carrageenin-induced paw edema (CPE) was also determined for representative structures. In the above series of experiments, we find that all the compounds showed moderate to satisfying interaction with the stable DPPH free radical in relation to the concentration and the time 2-arylidene-1-indandione (10) was the strongest. We observed moderate or very low antioxidant activities for selected compounds in the decolorization assay with ABTS+•. Most of the compounds showed high anti-lipid peroxidation of linoleic acid induced by AAPH.2-arylidene-1-indandione (7) showed a strongly inhibited soybean LOX. Only 2-arylidene-1-indandione (3) showed moderate scavenging activity of superoxide anion, whereas 2-arylidene-1-indandione (8) and 2-arylidene-1-indandione (9) showed very strong inhibition on proteolysis. 2-arylidene-1-indandione (8) highly inhibited serine protease thrombin. 2-arylidene-1-indandiones (7, 8 and 9) can be used as lead multifunctional molecules. The compounds were active for the inhibition of the CPE (30-57%) with 2-arylidene-1-indandione (1) being the most potent (57%). According to the predicted results a great number of the derivatives can cross the Blood-Brain Barrier (BBB), act in CNS and easily transported, diffused, and absorbed. Efforts are conducted a) to correlate quantitatively the in vitro/in vivo results with the most important physicochemical properties of the structural components of the molecules and b) to clarify the correlation of actions among them to propose a possible mechanism of action. Hydration energy as EHYDR and highest occupied molecular orbital (HOMO) better describe their antioxidant profile whereas the lipophilicity as RM values governs the in vivo anti-inflammatory activity. Docking studies are performed and showed that soybean LOX oxidation was prevented by blocking into the hydrophobic domain the substrates to the active site.


Assuntos
Anti-Inflamatórios/síntese química , Antioxidantes/síntese química , Edema/tratamento farmacológico , Indanos/síntese química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Barreira Hematoencefálica , Carragenina/efeitos adversos , Edema/induzido quimicamente , Feminino , Indanos/química , Indanos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Modelos Moleculares , Simulação de Acoplamento Molecular , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/química , Proteína-Lisina 6-Oxidase/antagonistas & inibidores , Proteína-Lisina 6-Oxidase/química , Ratos , Soja/enzimologia
5.
Molecules ; 25(1)2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31861583

RESUMO

Inflammation and oxidative stress are involved in cardiovascular diseases. Nitrogen monoxide participates in the regulation of endothelial processes. Thus, derivatives of classic nonsteroidal anti-inflammatory drugs (NSAIDs), trolox or cinnamic acids esterified with 2-(nitrooxy)ethanol were designed and studied. It was found that the nitrogen monoxide (NO) releasing activity was comparable to that of S-nitroso-N-acetylpenicillamine. The nitrooxy derivatives decreased potently lipid indices in the plasma of hyperlipidaemic rats (30-85%). All compounds presented increased anti-inflammatory activity in vivo, inhibiting carrageenan-induced rat paw oedema as high as 76%, up to six times higher than that of the parent acids. Lipoxygenase inhibitory activity was significant for most of them, although the parent molecules exerted a minor effect (IC50 > 0.2 mM). Those compounds incorporating an antioxidant structure inhibited rat microsomal membrane lipid peroxidation strongly and possessed radical scavenging activity. These results indicated that the described compounds could act at different targets in multifactorial diseases, further limiting the possible adverse effects of drug combinations.


Assuntos
Anti-Inflamatórios/síntese química , Antioxidantes/síntese química , Cromanos/química , Cinamatos/química , Inflamação/tratamento farmacológico , Doadores de Óxido Nítrico/síntese química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Carragenina/efeitos adversos , Modelos Animais de Doenças , Esterificação , Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Lipoxigenase/genética , Estrutura Molecular , Doadores de Óxido Nítrico/química , Doadores de Óxido Nítrico/farmacologia , Ratos
6.
PLoS One ; 14(10): e0223265, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31574117

RESUMO

Electrical impedance myography (EIM) is a technique for the assessment of muscle health and composition and has been shown to be sensitive to a variety of muscle pathologies including neurogenic atrophy and connective tissue deposition. However, it has been minimally studied in pure inflammation. In this study, we sought to assess EIM sensitivity to experimental inflammation induced by the localized intramuscular injection of λ-carrageenan. A total of 91 mice underwent 1-1000 kHz EIM measurements of gastrocnemius using a needle array, followed by injection of either 0.3% λ-carrageenan in phosphate-buffered saline (PBS) or PBS alone. Animals were then remeasured with EIM at 4, 24, 48, or 72 hours and euthanized and quantitative assessment of muscle histology was performed. Parallel alterations in both 5 and 50 kHz EIM values were identified at 4 and 24 hours, including reductions in phase, reactance, and resistance. In PBS-treated animals these values normalized by 48 hours, whereas substantial reductions in phase and reactance in 5 kHz EIM values persisted at 48 and 72 hours (i.e., values of phase 72 hours post-injection were 6.51 ± 0.40 degrees for λ-carrageenan versus 8.44 ± 0.35 degrees for PBS p<0.001, n = 11 per group). The degree of basophilic area observed in muscle sections by histology correlated to the degree of phase change at these two time points (Rspearman = -0.51, p = 0.0029). Changes in low frequency EIM parameters are sensitive to the presence of inflammatory infiltrates, and have the potential of serving as a simple means of quantifying the presence and extent of muscle inflammation without the need for biopsy.


Assuntos
Carragenina/efeitos adversos , Impedância Elétrica , Miografia , Miosite/etiologia , Miosite/fisiopatologia , Animais , Humanos , Masculino , Camundongos , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Miosite/diagnóstico
7.
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
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.
Eur Rev Med Pharmacol Sci ; 23(15): 6744-6752, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31378918

RESUMO

OBJECTIVE: The objective of this study was to assess safety, satisfaction, and anti-viral effect of a new carrageenan-based vaginal microbicide in a population of fertile female patients with genital human papillomavirus (HPV) infection. PATIENTS AND METHODS: Forty healthy and sexually active women aged 18-45 years with genital HPV infection were enrolled. Each subject was treated with a gel formulated with 0.02% carrageenan and Propionibacterium extract (CGP) (Carvir, Depofarma SpA, Mogliano Veneto, Treviso, Italy). The subjects were evaluated at baseline, after the I cycle of therapy and after the II cycle. At final status, treatment acceptability and satisfaction were evaluated using a 5-point Likert scale. Furthermore, the rate of HPV genital infection clearance at final follow-up was evaluated. These data were compared with the HPV genital infection clearance rate in a control group of patients not subjected to any therapy. RESULTS: Overall, 68 HPV infections were detected at baseline, among 40 subjects enrolled. The HPV 16 genotype was the most frequent (12%) followed by HPV 18 (10%), and HPV 53 (9%). At the end of the study, 22 (55%) patients were very satisfied, 14 (35%) were satisfied, 3 (7.5%) were uncertain, and only 1 (2.5%) was dissatisfied, with 0 very dissatisfied. Only 2 patients complained of a local adverse event. Analysing infection clearance at the end of the study, 60% of patients became HPV negative. Among these, 13 cases were high-risk HPV infection. There were 16 patients with persistent infection ("non-responders"). No patient developed a "de novo" genital lesion. After controlling for age, the intervention had an adjusted OR of 4.9 (95% CI 1.6-15.1) to clear HPV. CONCLUSIONS: The results of this work suggest that Carvir vulvovaginal microbicide gel is safe and well-tolerated. Furthermore, this experience supports the hypothesis that CG has a role in accelerating the normal clearance of genital HPV infection in women with a positive HPV-DNA test.


Assuntos
Anti-Infecciosos/administração & dosagem , Carragenina/administração & dosagem , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/tratamento farmacológico , Administração Intravaginal , Adolescente , Adulto , Anti-Infecciosos/efeitos adversos , Carragenina/efeitos adversos , Estudos de Casos e Controles , Chondrus/química , Colposcopia , DNA Viral/isolamento & purificação , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Satisfação do Paciente , Estudos Prospectivos , Alga Marinha/química , Resultado do Tratamento , Vagina/diagnóstico por imagem , Vagina/efeitos dos fármacos , Vagina/virologia , Cremes, Espumas e Géis Vaginais/administração & dosagem , Adulto Jovem
10.
Phytomedicine ; 60: 152987, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31257118

RESUMO

BACKGROUND: Urinary tract infections are among the most common types of infections and give rise to inflammation with pain as one of the main symptoms. The herbal medicinal product Canephron® N contains BNO 2103, a defined mixture of pulverized rosemary leaves, centaury herb, and lovage root, and has been used in the treatment of urinary tract infections for more than 25 years. PURPOSE: To test the hypothesis that BNO 2103 reduces pain in cystitis and prostatitis by virtue of anti-inflammatory properties, and to reveal potential mechanisms underlying the anti-inflammatory features. STUDY DESIGN: BNO 2103 was studied for anti-inflammatory and analgesic properties in three animal models in vivo, and the mode of action underlying the anti-inflammatory features was investigated in human leukocytes and cell-free assays in vitro. METHODS: To assess the anti-inflammatory and analgesic efficacy of BNO 2103 we employed cyclophosphamide-induced cystitis and carrageenan-induced prostatitis in rats, and zymosan-induced peritonitis in mice. Human neutrophils and monocytes as well as isolated human 5-lipoxygenase and microsomal prostaglandin E2 synthase-1-containing microsomes were utilized to assess inhibition of leukotriene and/or prostaglandin E2 production by HPLC and/or ELISA. RESULTS: When given orally, BNO 2103 reduced inflammation and hyperalgesia in experimental cystitis in rats, while individual components of BNO 2103 also reduced hyperalgesia. Furthermore, BNO 2103 reduced hyperalgesia in rats with carrageenan-induced prostatitis. Cell-based and cell-free studies implicate inhibition of prostaglandin E2 and leukotriene B4 biosynthesis as potential mechanisms underlying the analgesic and anti-inflammatory effects. CONCLUSION: Our data support the hypothesis that BNO 2103 reduces pain by virtue of its anti-inflammatory properties, possibly related to suppression of prostaglandin E2 and leukotriene B4 formation, and suggest that this combination has the potential to treat clinical symptoms such as inflammatory pain. Thus BNO 2103 may represent an alternative to reduce the use of antibiotics in urinary tract infections.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Cistite/complicações , Dor/tratamento farmacológico , Extratos Vegetais/farmacologia , Prostatite/complicações , Analgésicos/química , Animais , Anti-Inflamatórios/química , Carragenina/efeitos adversos , Ciclofosfamida/efeitos adversos , Cistite/induzido quimicamente , Medicamentos de Ervas Chinesas , Feminino , Humanos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Inflamação/tratamento farmacológico , Inflamação/etiologia , Masculino , Camundongos , Monócitos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Dor/etiologia , Extratos Vegetais/química , Prostatite/induzido quimicamente , Ratos , Ratos Sprague-Dawley
11.
Drug Dev Res ; 80(5): 666-679, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31112325

RESUMO

Inflammation is the response of the body to noxious stimuli such as infections, trauma, or injury. Experimental studies have shown that vanillic acid has anti-inflammatory effects. The objective of this study was to investigate the anti-inflammatory and antipyretic properties of the derivative of vanillic acid, isopropyl vanillate (ISP-VT), in mice. The results of this study indicated that ISP-VT reduced paw edema induced by carrageenan, dextran sulfate (DEX), compound 48/80, serotonin, bradykinin (BK), histamine (HIST), and prostaglandin E2 (PGE2). Furthermore, ISP-VT reduced recruitment of leukocytes and neutrophils and reduced its adhesion and rolling, and decreased myeloperoxidase enzyme activity (MPO), cytokine levels (tumor necrosis factor-α and interleukin-6), and vascular permeability. ISP-VT also significantly reduced the expression of cyclooxygenase-2 (COX-2) in subplantar tissue of mice. ISP-VT inhibited COX-2 selectively compared to the standard drug. Our results showed that although ISP-VT binds to COX-1, it is less toxic than indomethacin, as evidenced by MPO analysis of gastric tissue. Treatment with the ISP-VT significantly reduced rectal temperature in yeast-induced hyperthermia in mice. Our results showed that the main mechanism ISP-VT-induced anti-inflammatory activity is by inhibition of COX-2. In conclusion, our results indicate that ISP-VT has potential as an anti-inflammatory and antipyretic therapeutic compound.


Assuntos
Anti-Inflamatórios/administração & dosagem , Carragenina/efeitos adversos , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inflamação/tratamento farmacológico , Fenóis/efeitos adversos , Ácido Vanílico/química , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anticorpos Monoclonais/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Modelos Animais de Doenças , Feminino , Inflamação/induzido quimicamente , Inflamação/metabolismo , Injeções Intraperitoneais , Masculino , Camundongos , Modelos Moleculares , Fenóis/síntese química , Fenóis/química , Fenóis/farmacologia , Bibliotecas de Moléculas Pequenas/administração & dosagem , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia
12.
Molecules ; 24(6)2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30917586

RESUMO

The purpose of this research was to extract and separate the compounds from frankincense, and then evaluate their anti-inflammatory effects. The isolated compound was a representative tetracyclic triterpenes of glycine structure according to ¹H-NMR and 13C-NMR spectra, which is ß-elemonic acid (ß-EA). We determined the content of six different localities of frankincense; the average content of ß-EA was 41.96 mg/g. The toxic effects of ß-EA administration (400, 200, 100 mg/kg) for four weeks in Kunming (KM) mice were observed. Compared with the control group, the body weight of mice, the visceral coefficients and serum indicators in the ß-EA groups showed no systematic variations. The anti-inflammatory effects of ß-EA were evaluated in LPS-induced RAW264.7 cells, xylene-induced induced ear inflammation in mice, carrageenin-induced paw edema in mice, and cotton pellet induced granuloma formation in rats. ß-EA inhibited overproduction of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1), soluble TNF receptor 1 (sTNF R1), Eotaxin-2, Interleukin 10 (IL-10) and granulocyte colony-stimulating factor (GCSF) in the RAW264.7 cells. Intragastric administration with ß-EA (300, 200, and 100 mg/kg in mice, and 210, 140, and 70 mg/kg in rats) all produced distinct anti-inflammatory effects in vivo in a dose-dependent manner. Following treatment with ß-EA (300 mg/kg, i.g.), the NO level in mice ears and PGE2 in mice paws both decreased (p < 0.01). In conclusion, our study indicates that ß-EA could be a potential anti-inflammatory agent for the treatment of inflammatory diseases.


Assuntos
Anti-Inflamatórios/administração & dosagem , Dinoprostona/metabolismo , Franquincenso/química , Inflamação/tratamento farmacológico , Triterpenos/administração & dosagem , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Carragenina/efeitos adversos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Técnicas In Vitro , Inflamação/induzido quimicamente , Lipopolissacarídeos/efeitos adversos , Camundongos , Óxido Nítrico/metabolismo , Células RAW 264.7 , Ratos , Triterpenos/química , Triterpenos/farmacologia , Xilenos/efeitos adversos
13.
Int J Food Sci Nutr ; 70(6): 725-737, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30775939

RESUMO

This study sought to determine the possible detrimental effects of several low- or non-caloric sweeteners on endothelial progenitor cells (EPCs), inflammation and behavioural changes in mice. C57BL/6 male mice received low and high dose of natural and artificial sweeteners for 4 weeks. EPCs, physical and biochemical variables, inflammation and behavioural changes were evaluated. A significant reduction of about 25% of EPCs was found when mice received a moderate amount of all sweeteners (p < .05). This reduction was more strongly significant when a double dose of glucose, aspartame, rebaudioside A and cyclamate (p < .005) in comparison to fructose and sucrose (p < .05) was administered. During inflammation carrageenan-induced, all sweeteners produced a significant increase of EPCs compared to the control group (p < .05). Consumption of glucose and sugar substitutes affect mouse EPC number according to the absence or presence of an inflammatory status, but does not induce detrimental effects on inflammation and behavioural changes.


Assuntos
Comportamento Animal/efeitos dos fármacos , Células Progenitoras Endoteliais/efeitos dos fármacos , Inflamação/tratamento farmacológico , Edulcorantes/farmacologia , Animais , Ansiedade , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal , Carragenina/efeitos adversos , Comportamento Compulsivo , Diterpenos de Caurano/farmacologia , Frutose , Glucose , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Comportamento Obsessivo , Soro/química , Memória Espacial/efeitos dos fármacos , Sacarose
14.
Food Funct ; 10(3): 1760-1762, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30794268

RESUMO

Carrageenan (CGN) is a polysaccharide that is found in various types of sea weed. It is a common food additive used for its gelling and thickening properties and has been used safely throughout the world for decades. CGN is approved as Generally Recognized as Safe (GRAS) by the United States Food and Drug Administration and is also considered safe for the general population by the World Health Organizations Joint Expert Committee on Food Additive (JECFA) and the European Food Safety Authority. CGN has been tested for safety in various animal models for many years and more recently in an array of in vitro or cell-based models. A recent review published by this journal entitled "Revisiting the Carrageenan controversy: Do we really understand the digestive fate and safety of carrageenan in our foods?" has provided the impetus for this commentary (S. David, et al., Food Funct., 2018, 9(3), 1344-1352). It is important that our food is safe, and clearly there are examples of food additives that were found to be unsafe after years of use, but the issue is the need for accurate interpretation of previously published studies and the need for designing and conducting experiments that can be used to make decisions on safety. It is our hope that this commentary brings to light some of the important physical and chemical properties of CGN and how information can be easily misinterpreted.


Assuntos
Carragenina/efeitos adversos , Carragenina/química , Aditivos Alimentares/efeitos adversos , Aditivos Alimentares/química , Carragenina/metabolismo , Digestão , Aditivos Alimentares/metabolismo , Análise de Alimentos , Humanos
15.
Food Funct ; 10(3): 1763-1766, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30794278

RESUMO

This commentary re-emphasizes the aim of our recent review (David et al., 2018) and addresses some of the points raised in the adjacent commentary by M. Weiner and J. McKim, Food Funct., 2019, 10, DOI: 10.1039/C8FO01282B. In agreement with the commentary, the discussed review highlights the need to adequately understand the complex physicochemistry of the food additive carrageenan (CGN) and its fate in the alimentary canal. In fact, there is a realm of scientific findings that justify the continuation of an open discussion of CGN safety. This response emphasizes that there is sparse information on [i] the physicochemical properties of commercial CGN, [ii] human levels of exposure to CGN from foods, [iii] the role of CGN in gut microbiome dysbiosis and inflammation, and [iv] the effects of CGN on susceptible populations. As long as the determinants of the increased prevalence of chronic and autoimmune diseases are not identified, we must continue to explore the possible beneficial or deleterious effects that may arise from extrinsic factors, including food additives, and do so in meticulous independent studies.


Assuntos
Carragenina/efeitos adversos , Carragenina/química , Aditivos Alimentares/efeitos adversos , Aditivos Alimentares/química , Carragenina/metabolismo , Digestão , Aditivos Alimentares/metabolismo , Análise de Alimentos , Humanos
16.
Daru ; 27(1): 59-70, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30701460

RESUMO

OBJECTIVE: Clinical utility of lornoxicam in oral therapy is primarily restricted by the low solubility and gastric adverse effects. This study evaluated the prospective of optimized proniosomal gel to improve the clinical efficacy of lornoxicam and compare with oral therapy. METHODS: Proniosomes were formulated by coacervation phase separation technique using span 60, lecithin and cholesterol. A four-factor three-level Box-Behnken design was used to evaluate the effect of amount of four independent variables; span 60 (X1), cholesterol (X2), lecithin (X3) and lornoxicam (X4) on response variables; vesicle size (Y1), entrapment efficiency (Y2) and transdermal flux (Y3). The selected proniosomal gel (F19) was characterized, and evaluated for the transdermal efficacy by ex vivo and in vivo experiments. RESULTS: Optimization study signifies that amount of formulation components (span 60, cholesterol, lecithin and lornoxicam) influence the vesicle size, entrapment efficiency and/or transdermal flux. Optimized formulation F19 exhibited nano size with high entrapment efficiency, adequate zeta potential, greater transdermal flux and better stability (at refrigerated conditions). The entrapment of lornoxicam in the bilayers of proniosome vesicles was confirmed by differential scanning calorimeter. Release profile of F19 was distinct (p < 0.001) from gel prepared using hydroxypropyl methylcellulose (control) and displayed steady lornoxicam release by Fickian diffusion. Transdermal administration of F19 significantly inhibited the carrageenan induced hind-paw edema in rats as compared to oral lornoxicam group. CONCLUSIONS: The data observed in this study demonstrated that the developed proniosomal gel (F19) improved the clinical efficacy of lornoxicam as compared to oral therapy. Graphical Abstract Proniosomal gel for transdermal delivery of lornoxicam: optimization using factorial design and in vivo evaluation in rats.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Carragenina/efeitos adversos , Inflamação/tratamento farmacológico , Piroxicam/análogos & derivados , Administração Cutânea , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/química , Varredura Diferencial de Calorimetria , Composição de Medicamentos , Géis , Inflamação/induzido quimicamente , Lipossomos , Piroxicam/administração & dosagem , Piroxicam/química , Ratos
17.
Phytomedicine ; 52: 272-283, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30599908

RESUMO

BACKGROUND: Berberine (BBR) is the most abundant and major active constituent of Rhizoma Coptidis (RC), which has been widely used to treat inflammatory diseases in traditional oriental medicine. Despite BBR has been found to exhibit pronounced anti-inflammatory effect, the anti-inflammatory activities of its natural derivatives were sparsely dissected out. PURPOSE: To comparatively investigate the anti-inflammatory potential of BBR, and its natural oxoderivative (oxyberberine, OBB) and reduced derivative (dihydroberberine, DHBB) in vitro and in vivo, and delineate the possible underlying mechanism. METHODS: LC-MS/MS was used to identify the natural derivatives of BBR in RC. The potential anti-inflammatory properties of BBR and its natural derivatives were comparatively evaluated in vitro by lipopolysaccharide (LPS)-induced RAW264.7 macrophages cells, and in vivo via three typical acute inflammation murine models. Some important inflammation-related molecules were analyzed by ELISA, qRT-PCR and Western blotting. RESULTS: LC-MS/MS led to the identification of BBR, OBB and DHBB in RC ethyl acetate extract. The in vitro assay indicated that BBR, OBB and DHBB (1.25, 2.5 and 5 µM) pretreatment significantly decreased the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), prostaglandinE2 (PGE2) and nitricoxide (NO), and inhibited the mRNA expressions of cyclooxygenase-2 (COX-2) and inducible nitricoxide synthase (iNOS) in a dose-dependent manner, with relative efficiency of OBB > BBR > DHBB. Furthermore, OBB, BBR and DHBB remarkably inhibited the phosphorylation of nuclear factor-κB (NF-κB) p65 and inhibitory kappa Bα (IκBα). In vivo, BBR (20 mg/kg) and OBB (5, 10, and 20 mg/kg) pretreatment significantly ameliorated the xylene-induced ear edema, carrageenan-stimulated paw edema, and acetic acid-elicited vascular permeability in mice in a dose-dependent manner, with OBB exhibiting superior anti-inflammatory effect at the same dose (20 mg/kg). Histopathological analysis indicated that OBB and BBR could markedly attenuate the inflammatory deterioration and decrease the cellular infiltration in paw tissues. Additionally, the carrageenan-induced increases in TNF-α, IL-6, IL-1ß, PGE2 and NO productions, and COX-2 and iNOS mRNA expressions were effectually and concentration-dependently suppressed by OBB and BBR pretreatment. CONCLUSION: The anti-inflammatory activity of BBR and its natural derivatives was in the order of OBB > BBR > DHBB. OBB was for the first time found to be endowed with pronounced anti-inflammatory property, which was probably associated with suppressing the activation of NF-κB signaling pathway, and the subsequent gene expressions and productions of pro-inflammatory mediators. The results might contribute to illuminating the pharmacodynamic underpinnings of RC and provide evidence for developing OBB as a safe and promising natural lead compound in inflammation treatment.


Assuntos
Anti-Inflamatórios/farmacologia , Berberina/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Animais , Berberina/análogos & derivados , Carragenina/efeitos adversos , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Feminino , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Inibidor de NF-kappaB alfa/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
18.
Curr Org Synth ; 16(8): 1161-1165, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31984922

RESUMO

BACKGROUND: Recently, there has been a lot of scientific interest in exploring the syntheses of oxygen and nitrogen-containing heterocyclic compounds due to their pharmacological activities. In addition, benzisoxazoles play a very important role in organic synthesis as key intermediates. OBJECTIVE: In this paper, we focused on developing a novel synthetic route for biologically active arylisoxazoles under normal conditions, and simplified it to get high purities and yields, and also reported their anti-inflammatory activities. METHODS: An efficient and simple method has been explored for the synthesis of novel 3-methyl arylisoxazoles from o-nitroaryl halides via o-ethoxyvinylnitroaryls, using dihydrated stannous chloride (SnCl2.2H2O) in MeOH / EtOAc (1:1) via Domino rearrangement in one pot synthesis. RESULTS: We synthesized novel 3-methylarylisoxazoles from o-nitroarylhalides via o-ethoxyvinylnitroaryls, using dihydrated stannous chloride (SnCl2.2H2O) in MeOH / EtOAc (1:1) via domino rearrangement. In this reduction, nitro group and ethoxy vinyl group change to the functional acyl ketones, followed by hetero cyclization. Here, the reaction proceeds without the isolation of intermediates like 2-acylnitroarenes and 2- acylanilines. All the synthesized compounds were completely characterized by the NMR and mass spectra. The compounds were also explored for their anti-inflammatory activity by carrageenan-induced inflammation in the albino rats (150-200 g) of either sex used in this entire study with the use of Diclofenac sodium as the standard drug. The initial evaluations identified leading targets with good to moderate anti-inflammatory activity. CONCLUSION: A simple, one-pot and convenient method has been explored for the synthesis of novel 3- methylarylisoxazoles with high purity and reaction yields. All the compounds 3a, 3c, 3d, 3f, 3g and 3h exhibited 51-64% anti-inflammatory activities.


Assuntos
Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacologia , Isoxazóis/síntese química , Isoxazóis/farmacologia , Animais , Carragenina/efeitos adversos , Carragenina/química , Complexos de Coordenação/química , Ciclização , Diclofenaco/química , Diclofenaco/farmacologia , Modelos Animais de Doenças , Desenho de Fármacos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Cetonas/química , Estrutura Molecular , Oxirredução , Ratos , Relação Estrutura-Atividade , Compostos de Estanho/química
19.
Molecules ; 23(10)2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30248903

RESUMO

Non-steroidal anti-inflammatory drugs (NSAIDs) are an important pharmacological class of drugs used for the treatment of inflammatory diseases. They are also characterized by severe side effects, such as gastrointestinal damage, increased cardiovascular risk and renal function abnormalities. In order to synthesize new anti-inflammatory and analgesic compounds with a safer profile of side effects, a series of 2,6-diaryl-imidazo[2,1-b][1,3,4]thiadiazole derivatives 5a⁻l were synthesized and evaluated in vivo for their anti-inflammatory and analgesic activities in carrageenan-induced rat paw edema. Among all compounds, 5c showed better anti-inflammatory activity compared to diclofenac, the standard drug, and compounds 5g, 5i, 5j presented a comparable antinociceptive activity to diclofenac. None of the compounds showed ulcerogenic activity. Molecular docking studies were carried out to investigate the theoretical bond interactions between the compounds and target, the cyclooxygenases (COX-1/COX-2). The compound 5c exhibited a higher inhibition of COX-2 compared to diclofenac.


Assuntos
Analgésicos/síntese química , Anti-Inflamatórios não Esteroides/síntese química , Edema/tratamento farmacológico , Imidazóis/síntese química , Tiadiazóis/síntese química , Analgésicos/administração & dosagem , Analgésicos/química , Analgésicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Carragenina/efeitos adversos , Ciclo-Oxigenase 1/química , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/metabolismo , Diclofenaco/administração & dosagem , Diclofenaco/uso terapêutico , Edema/induzido quimicamente , Feminino , Imidazóis/administração & dosagem , Imidazóis/química , Imidazóis/farmacologia , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Conformação Molecular , Simulação de Acoplamento Molecular , Estrutura Molecular , Ratos , Relação Estrutura-Atividade , Tiadiazóis/administração & dosagem , Tiadiazóis/química , Tiadiazóis/farmacologia
20.
Phytomedicine ; 47: 58-68, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30166109

RESUMO

BACKGROUND: Passiflora cincinnata Mast. is described as a native species from the Caatinga biome, and used by traditional medicine for several pharmacological purposes, such as inflammatory disorders. However, studies that prove its biological activities are scarce. HYPOTHESIS/PURPOSE: This paper aims to evaluate the antinociceptive and anti-inflammatory activities of the aerial parts of Passiflora cincinnata (Pc-EtOH) in mice. METHODS: The chemical composition of Pc-EtOH was assessed by high-performance liquid chromatography coupled to diode array detector (HPLC-DAD). The antinociceptive profile of the extract (given orally: 100, 200 and 400 mg/kg) was established using the in vivo chemical models (acetic acid-induced abdominal constriction and formalin-induced paw licking test) and thermal (hot plate test) of nociception. The role of opioid, potassium channels, TRPV-1, muscarinic, serotoninergic (5-HT3) receptors and the participation of the nitric oxide pathway also was determined. The rota-rod test was used to verify the possible interference of the extract treatment in motor performance. Paw edema induced by carrageenan or histamine, and leukocyte migration, determination of total protein and nitric oxide to the peritoneal cavity were used for anti-inflammatory profile. RESULTS: The presence of flavonoids in the extract was confirmed using HPLC-DAD. At all doses tested the Pc-EtOH significantly reduced the number of writhing and decreased the paw licking time in both phases of the formalin test (p < 0.05). In the hot plate test, the extract increased the reaction time, reducing painful behavior. The antinociceptive mechanism probably involves central and peripheral pathways, involving the pathway of opioid and muscarinic receptors with influence of potassium channels and the nitric oxide pathway. However, the motor coordination test indicated that in the time of 120 min the extract decreases the stay time of the animal in the rota-rod. Pc-EtOH inhibited significantly (p < 0.05) the increase of the edema volume after administration of carrageenan and histamine. In the peritonitis test, acute pre-treatment with Pc-EtOH inhibited leukocyte migration, with a reduction in the number of neutrophils and concentration of total proteins and nitric oxide. CONCLUSION: The present study suggests that Pc-EtOH possesses peripheral and central antinociceptive action, and showed potential in inhibition of release of mediators of the inflammatory process.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Passiflora/química , Extratos Vegetais/farmacologia , Animais , Carragenina/efeitos adversos , Edema/tratamento farmacológico , Etanol/efeitos adversos , Flavonoides/uso terapêutico , Masculino , Camundongos , Nociceptividade/efeitos dos fármacos , Dor/tratamento farmacológico , Medição da Dor , Componentes Aéreos da Planta/química
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