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1.
Int J Mol Sci ; 21(5)2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32120831

RESUMO

Methamphetamine (METH) is an addictive psychostimulant showing neurotoxicity through neuronal apoptosis and the neuro-inflammatory pathway. Lupenone, a lupane triterpenoid, is an isolated compound exhibiting anti-oxidative, anti-inflammation, and anti-diabetic activities. However, whether lupenone plays a protective role against apoptosis induced by METH in SH-SY5y neuroblastoma cells remains unknown. In the present study, we elucidated that lupenone had no toxicity to SH-SY5y cells at different concentrations. On the other hand, we found that the treatment of SH-SY5y cells with an optimal concentration of lupenone could lead to protection against cell death induced by METH. AnnexinV/PI apoptosis analysis revealed a dramatically reduced level of the apoptotic cell population in lupenon and METH treated SH-SY5y cells. Moreover, diminished expression of anti-apoptotic proteins, including Bcl-2, Caspase3, Caspase7, and Caspase8 in METH-exposed SH-SY5y cells, was significantly recovered by treatment with lupenone. This protection in the expression of anti-apoptotic proteins was due to an increased phosphorylation level of PI3K/Akt in METH-treated SH-SY5y cells pre-incubated with lupenone. These findings suggest that lupenone can protect SH-SY5y cells against METH-induced neuronal apoptosis through the PI3K/Akt pathway.

2.
Molecules ; 25(3)2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32033079

RESUMO

Recently, many natural products with unique structure and promising pharmacological potential have been reported from marine-derived microorganisms. The macrolactin A (MA), 15-epi-dihydromacrolactin F (DMF) and macrolactin F (MF) were obtained from the culture broth extract of a marine sediment derived microorganism Bacillus sp. HC001. In this study, MA, DMF and MF inhibited the production and expression of proinflammatory mediators of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW264.7 and BV2 cells. Also, MA, DMF and MF exert anti-inflammatory effects through the expression of heme oxygenase (HO) -1, a stress-inducing enzyme that converts heme to carbon monoxide (CO), iron and biliberdine. Toll-like receptor 4 (TLR4) expressed by lipopolysaccharide (LPS) was inhibited by increased expression of HO-1 transcription factor Nrf2 and down regulation of BTB Domain And CNC Homolog 1 (BACH1), inhibited phosphorylation of Mitogen-activated protein kinase kinase kinase 7 (MAP3K7, TAK1) and nuclear factor kappaB (NF-κB). These results show that MA, DMF and MF effectively inhibited TLR4 by regulating BACH1 and HO-1/Nrf2 signals in LPS-stimulated RAW264.7 and BV2 cells, which suggests the possibility of use as an anti-inflammatory agent.

3.
J Ethnopharmacol ; 250: 112484, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-31843576

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: A promising approach to treat a variety of diseases are considered as complementary and alternative herbal medicines. Prunus serrulata var. spontanea L. (Rosaceae) is used as herbal medicine to treat allergic diseases according to the Donguibogam, a tradition medical book of the Joseon Dynasty in Korea. AIM OF THE STUDY: We prepared the aqueous extract of the bark of P. serrulata (AEBPS) and aimed to investigate the effects in mouse anaphylaxis models and various types of mast cells, including RBL-2H3, primary cultured peritoneal and bone marrow-derived mast cells. MATERIALS AND METHODS: We used ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) and immunoglobulin (Ig) E-mediated passive cutaneous anaphylaxis (PCA) models, in vivo. The control drug dexamethasone (10 mg/kg) was used to compare the effectiveness of AEBPS (1-100 mg/kg). In vitro, IgE-stimulated mast cells were used to confirm the role of AEBPS (1-100 µg/mL). For statistical analyses, p values less than 0.05 were considered to be significant. RESULTS: In ASA model, oral administration of AEBPS suppressed the hypothermia and increased level of serum histamine in a dose-dependent manner. AEBPS attenuated the serum IgE, OVA-specific IgE, and interleukin (IL)-4. Oral administration of AEBPS also blocked mast cell-dependent PCA. AEBPS suppressed degranulation of mast cells by reducing intracellular calcium level in mast cells. AEBPS inhibited tumor necrosis factor-α and IL-4 expression and secretion in a concentration-dependent manner through the reduction of nuclear factor-κB. CONCLUSIONS: On the basis of these findings, AEBPS could serve as a potential therapeutic target for the management of mast cell-mediated allergic inflammation and as a regulator of mast cell activation.

4.
Phytother Res ; 33(11): 2948-2959, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31478281

RESUMO

The balance between the osteoblasts and the osteoclasts is important for the maintenance of the skeleton of the human body. The osteoclasts absorb bone after differentiated into polymorphonuclear cells by the fusion of monocytes/macrophages. We have found that 6,7,4'-Trihydroxyflavone (THF), a compound from the heartwood of Dalbergia Odorifera inhibits receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation, actin ring formation, and bone resorption in RAW 264.7 cells and bone marrow macrophage. THF significantly inhibited the c-Jun-N-terminal kinase signaling pathway without affecting extracellular signal-regulated kinase, p38, and AKT signaling. Moreover, THF inhibited the expression of c-Fos, nuclear factor-activated T cells cytoplasm 1, cathepsin K, and c-src by RANKL. We used a lipopolysaccharide (LPS)-induced bone loss model in mice. Consequently, bone volume per tissue volume, trabecular number's reduction was recovered in THF-treated mice, and trabecular separation's augmentation was also attenuated by THF administration. In summary, THF inhibits RANKL-induced osteoclast differentiation by MAPK signaling pathway and inhibits bone resorption by destroying the actin ring in mature osteoclasts. THF also prevented LPS-induced bone loss in a mice model. Thus, THF may be useful in the treatment of bone diseases associated with excessive osteoclast differentiation and bone resorption.


Assuntos
Reabsorção Óssea/prevenção & controle , Diferenciação Celular/efeitos dos fármacos , Isoflavonas/farmacologia , Osteoclastos/efeitos dos fármacos , Animais , Células Cultivadas , Dalbergia/química , MAP Quinases Reguladas por Sinal Extracelular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Osteoblastos/efeitos dos fármacos , Osteoblastos/fisiologia , Osteoclastos/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
5.
Int J Environ Health Res ; : 1-14, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31407590

RESUMO

Particulate matter 2.5 (PM2.5), aerodynamic diameter ≤ 2.5 µm, is the primary air pollutant that plays the key role for lung injury resulted from the loss of vascular barrier integrity. Cudratricusxanthone O (CTXO) is a novel xanthone compound isolated from the root of Cudrania tricuspidata Bureau. Here, we investigated the beneficial effects of CTXO against PM-induced lung endothelial cell (EC) barrier disruption and pulmonary inflammation. Permeability, leukocyte migration, activation of proinflammatory proteins, generation of reactive oxygen species (ROS), and histology were examined in PM2.5-treated ECs and mice. CTXO significantly scavenged PM2.5-induced ROS and inhibited the ROS-induced activation of p38 mitogen-activated protein kinase (MAPK). Concurrently, CTXO activated Akt, which helped maintain endothelial integrity. Furthermore, CTXO reduced vascular protein leakage, leukocyte infiltration, and proinflammatory cytokine release in the bronchoalveolar lavage fluid in PM-induced lung tissues. These results indicated that CTXO may exhibit protective effects against PM-induced inflammatory lung injury and vascular hyperpermeability.

6.
Front Pharmacol ; 10: 869, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31427975

RESUMO

Mast cells are effector cells that induce allergic inflammation by secreting inflammatory mediators. Gomisin M2 (G.M2) is a lignan isolated from Schisandra chinensis (Turcz). Baill. exhibiting anti-cancer activities. We aimed to investigate the anti-allergic effects and the underlying mechanism of G.M2 in mast cell-mediated allergic inflammation. For the in vitro study, we used mouse bone marrow-derived mast cells, RBL-2H3, and rat peritoneal mast cells. G.M2 inhibited mast cell degranulation upon immunoglobulin E (IgE) stimulation by suppressing the intracellular calcium. In addition, G.M2 inhibited the secretion of pro-inflammatory cytokines. These inhibitory effects were dependent on the suppression of FcεRI-mediated activation of signaling molecules. To confirm the anti-allergic effects of G.M2 in vivo, IgE-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin-induced active systemic anaphylaxis (ASA) models were utilized. Oral administration of G.M2 suppressed the PCA reactions in a dose-dependent manner. In addition, G.M2 reduced the ASA reactions, including hypothermia, histamine, interleukin-4, and IgE production. In conclusion, G.M2 exhibits anti-allergic effects through suppression of the Lyn and Fyn pathways in mast cells. According to these findings, we suggest that G.M2 has potential as a therapeutic agent for the treatment of allergic inflammatory diseases via suppression of mast cell activation.

7.
Phytomedicine ; 43: 86-91, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29747758

RESUMO

BACKGROUND: Cudratricusxanthone A (CTXA) was isolated from Cudrania tricuspidata and its anti-inflammatory, hepatoprotective, and anti-proliferative activities have previously been studied in vitro. However, effects of CTXA on osteoclast differentiation have not been investigated. PURPOSE: In this study, the effect of CTXA from C. tricuspidata on in vitro osteoclastogenesis was studied. DESIGN/METHODS: CTXA was isolated from the roots of C. tricuspidata. The effects of CTXA on the RANKL-induced osteoclastogenesis, actin ring formation, and bone resorption were tested by using the RAW 264.7 cells and mouse bone marrow monocytes (BMMs). RESULTS: The structure of CTXA was identified by comparison with spectral data in the literature. We also checked the effect of CTXA on in vitro osteoclastogenesis. CTXA significantly inhibited the JNK/MAPK signaling pathway without affecting ERK and p38 signaling in RANKL-stimulated RAW 264.7 cells and BMMs. Moreover, it inhibited RANKL-induced expression of c-Fos and NFATc1. CONCLUSION: In conclusion, CTXA suppresses osteoclast differentiation by inhibiting RANKL-induced MAPK signaling and attenuates bone resorption by disrupting actin ring formation in mature osteoclasts. These results suggest that CTXA inhibits bone resorption through an inhibitory effect on osteoclast formation and function.


Assuntos
Osteoclastos/efeitos dos fármacos , Xantonas/química , Xantonas/farmacologia , Animais , Células da Medula Óssea/efeitos dos fármacos , Reabsorção Óssea/tratamento farmacológico , Diferenciação Celular/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Moraceae/química , Osteoclastos/citologia , Osteoclastos/fisiologia , Raízes de Plantas/química , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ligante RANK/metabolismo , Ligante RANK/farmacologia , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
8.
Stem Cells Int ; 2017: 5180579, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29250120

RESUMO

In cholestatic liver diseases, impaired bile excretion disrupts lipid homeostasis. We investigated changes of lipid metabolism, including mitochondrial ß-oxidation, in a rat model of bile duct ligation (BDL) in which chorionic plate-derived mesenchymal stem cells (CP-MSCs) were transplanted. Serum cholesterol level, which was elevated after BDL, was significantly decreased following CP-MSC transplantation. The expression levels of genes involved in intracellular lipid uptake, including long-chain fatty acyl-CoA synthetases and fatty acid transport proteins, were decreased in rats after BDL; however, they were not significantly changed by subsequent CP-MSC transplantation. Carnitine palmitoyltransferase 1A (CPT1A), a rate-limiting enzyme in mitochondrial ß-oxidation, was upregulated after BDL and then was downregulated after CP-MSC transplantation. CPT1A expression was changed via microRNA-33-a posttranscriptional regulator of CPT1A-in a peroxisome proliferator-activated receptor α-independent manner. Cellular adenosine triphosphate production-an indicator of mitochondrial function-was reduced after BDL and was restored by CP-MSC transplantation. Expression levels of heme oxygenases also were significantly affected following BDL and CP-MSC transplantation. Lipid metabolism is altered in response to chronic cholestatic liver injury and can be restored by CP-MSC transplantation. Our study findings support the therapeutic potential of CP-MSCs in cholestatic liver diseases and help in understanding the fundamental mechanisms by which CP-MSCs affect energy metabolism.

9.
BMC Complement Altern Med ; 14: 251, 2014 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-25034211

RESUMO

BACKGROUND: Drug transporters play important roles in the absorption, distribution, and elimination of drugs and thereby, modulate drug efficacy and toxicity. With a growing use of poly pharmacy, concurrent administration of herbal extracts that modulate transporter activities with drugs can cause serious adverse reactions. Therefore, prediction and evaluation of drug-drug interaction potential is important in the clinic and in the drug development process. DA-9801, comprising a mixed extract of Dioscoreae rhizoma and Dioscorea nipponica Makino, is a new standardized extract currently being evaluated for diabetic peripheral neuropathy in a phase II clinical study. METHOD: The inhibitory effects of DA-9801 on the transport functions of organic cation transporter (OCT)1, OCT2, organic anion transporter (OAT)1, OAT3, organic anion transporting polypeptide (OATP)1B1, OATP1B3, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP) were investigated in HEK293 or LLC-PK1 cells. The effects of DA-9801 on the pharmacokinetics of relevant substrate drugs of these transporters were also examined in vivo in rats. RESULTS: DA-9801 inhibited the in vitro transport activities of OCT1, OCT2, OAT3, and OATP1B1, with IC50 values of 106, 174, 48.1, and 273 µg/mL, respectively, while the other transporters were not inhibited by 300 µg/mL DA-9801. To investigate whether this inhibitory effect of DA-9801 on OCT1, OCT2, and OAT3 could change the pharmacokinetics of their substrates in vivo, we measured the pharmacokinetics of cimetidine, a substrate for OCT1, OCT2, and OAT3, and of furosemide, a substrate for OAT1 and OAT3, by co-administration of DA-9801 at a single oral dose of 1,000 mg/kg. Pre-dose of DA-9801 5 min or 2 h prior to cimetidine administration decreased the Cmax of cimetidine in rats. However, DA-9801 did not affect the elimination parameters such as half-life, clearance, or amount excreted in the urine, suggesting that it did not inhibit elimination process of cimetidine, which is governed by OCT1, OCT2, and OAT3. Moreover, DA-9801 did not affect the pharmacokinetic characteristics of furosemide, as evidenced by its unchanged pharmacokinetic parameters. CONCLUSION: Inhibitory effects of DA-9801 on OCT1, OCT2, and OAT3 observed in vitro may not necessarily translate into in vivo herb-drug interactions in rats even at its maximum effective dose.


Assuntos
Cimetidina/farmacocinética , Furosemida/farmacocinética , Interações Ervas-Drogas , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Preparações de Plantas/farmacologia , Animais , Furosemida/sangue , Células HEK293 , Humanos , Masculino , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Ratos , Ratos Sprague-Dawley
10.
Biomed Chromatogr ; 28(12): 1816-21, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24817673

RESUMO

Homoegonol is a biologically active neolignan isolated from Styrax species with cytotoxic, antimicrobial, anti-inflammatory and anti-asthma activities. For the quantification of homoegonol in rat plasma, a selective and sensitive liquid chromatography-tandem mass spectrometric method was developed and validated for the first time using protein precipitation with methanol as a sample clean-up procedure. The analytes were separated in an Atlantis dC18 column using a gradient elution of methanol and 0.1% formic acid, and mass-to-charge ratios were determined in selective reaction monitoring mode using tandem mass spectrometry with m/z 343.12 > 296.97 for homoegonol and m/z 517.30 > 282.90 for udenafil (internal standard). The standard curve was linear over the concentration ranges of 1 - 500 ng/mL using a 30 µL rat plasma sample. The coefficient of variation and relative error for intra- and inter-assay at four quality control levels were 3.9-10.0 and -3.3-2.7%, respectively. The overall recovery of homoegonol from rat plasma using protein precipitation was 99.7 ± 7.7%. The pharmacokinetics parameters of homoegonol were dose-independent after both intravenous (1, 2.5 and 5 mg/kg doses) and oral (5, 10 and 20 mg/kg doses) administration in male Sprague-Dawley rats.


Assuntos
Cromatografia Líquida/métodos , Lignanas/sangue , Lignanas/farmacocinética , Espectrometria de Massas em Tandem/métodos , Animais , Lignanas/química , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Styrax
11.
J Psychiatr Res ; 40(6): 541-9, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16083910

RESUMO

The implicit and explicit memory in patients with obsessive-compulsive disorder (OCD) was investigated using the event-related potential (ERP). For the assessment of implicit memory, a lexical decision task was administered. Among a total of 320 words and 140 non-words, 200 words were repeated, while the remaining 120 words and the 140 non-words were not repeated. For explicit memory, a continuous recognition task was administered, in which 280 words were repeated and 100 were not repeated. On the recognition task, both the controls and OCD patients showed more positivity to the old words than to the new words during the 200-600 ms period post-stimulus. Both groups showed faster response time to the old words than to the new words. On the lexical decision task, the controls showed the old/new effect during the 200-500 ms period post-stimulus, while the OCD patients did not. However, OCD patient showed faster response time to the old words than to the new words, although OCD patients showed prolonged response times to the old words compared to the controls. These results indicate that OCD patients have preserved explicit and implicit memory. The absence of old/new effect on ERP in OCD patients was discussed in terms of dysfunction of frontostriatal system, which plays an important role in both OCD and implicit memory.


Assuntos
Potenciais Evocados/fisiologia , Rememoração Mental/fisiologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , /fisiologia , Adulto , Mapeamento Encefálico , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Estimulação Luminosa/métodos , Tempo de Reação/fisiologia , Fatores de Tempo
12.
Psychophysiology ; 42(5): 616-25, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16176385

RESUMO

We investigated the characteristic changes in the physiology of cybersickness when subjects were exposed to virtual reality. Sixty-one participants experienced a virtual navigation for a total of 9.5 min, and were required to detect specific virtual objects. Three questionnaires for sickness susceptibility and immersive tendency were obtained before the navigation. Sixteen electrophysiological signals were recorded before, during, and after the navigation. The severity of cybersickness experienced by participants was reported from a simulator sickness questionnaire after the navigation. The total severity of cybersickness had a significant positive correlation with gastric tachyarrhythmia, eyeblink rate, heart period, and EEG delta wave and a negative correlation with EEG beta wave. These results suggest that cybersickness accompanies the pattern changes in the activities of the central and the autonomic nervous systems.


Assuntos
Cibernética , Enjoo devido ao Movimento/fisiopatologia , Orientação/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Interface Usuário-Computador , Adulto , Atenção/fisiologia , Sistema Nervoso Autônomo/fisiopatologia , Ritmo beta , Piscadela/fisiologia , Córtex Cerebral/fisiopatologia , Ritmo Delta , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Monitorização Fisiológica , Enjoo devido ao Movimento/psicologia , Estatística como Assunto , Estômago/inervação , Inquéritos e Questionários
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