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BACKGROUND: Lumbar degenerative kyphosis (LDK) is characterized by sagittal imbalance resulting from degenerative loss of lumbar lordosis. The ability of transcutaneous neuromuscular electrical stimulation (NMES) to activate deep lumbar stabilizing muscles has been demonstrated. OBJECTIVE: The aim of this study was to evaluate the effects of transcutaneous NMES applied to optimal points on the lower abdomen and lumbar paraspinal region on gait problems in patients with lumbar degenerative kyphosis (LDK). METHODS: Twenty-one patients with lumbar degenerative kyphosis underwent three walking sessions in the following order; walking for 5 minutes without NMES, walking with NMES on the lumbar multifidus (LM) only, and walking with NMES on both LM and transverse abdominis (TrA)/obliquus internus (OI). Differences in gait parameters at the commencement and completion of each of the three sessions were evaluated by gait analysis. RESULTS: During the 5-minute walk with NMES applied to the LM or to the LM and TrA/OI, participants showed lesser increases in spine forward tilt, pelvic anterior tilt, and external foot progression angle, and a lesser decrease in hip internal rotation than when walking without NMES (P< 0.05). In addition, with NMES, patients showed less decrement in gait velocity and stride length at walk completion than patients walking without NMES (P< 0.05). However, in the comparison between walks with NMES applied to the LM and walks with NMES applied to the LM and TrA/OI, we could not find any significant difference in changes of gait parameters (p> 0.05). CONCLUSIONS: Transcutaneous NMES applied at optimal points on the lower abdomen and back could provide a means of treating gait problems caused by a stooped trunk in LDK patients.
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Marcha/fisiología , Cifosis/fisiopatología , Cifosis/terapia , Estimulación Eléctrica Transcutánea del Nervio , Abdomen , Anciano , Femenino , Humanos , Vértebras Lumbares/fisiopatología , Región Lumbosacra , Persona de Mediana EdadRESUMEN
PURPOSE: Accurate information is essential in dentistry. The image information of missing teeth is used in optically based medical equipment in prosthodontic treatment. To evaluate oral scanners, the standardized model was examined from cases of image recognition errors of linear discriminant analysis (LDA), and a model that combines the variables with reference to ISO 12836:2015 was designed. MATERIALS AND METHODS: The basic model was fabricated by applying 4 factors to the tooth profile (chamfer, groove, curve, and square) and the bottom surface. Photo-type and video-type scanners were used to analyze 3D images after image capture. The scans were performed several times according to the prescribed sequence to distinguish the model from the one that did not form, and the results confirmed it to be the best. RESULTS: In the case of the initial basic model, a 3D shape could not be obtained by scanning even if several shots were taken. Subsequently, the recognition rate of the image was improved with every variable factor, and the difference depends on the tooth profile and the pattern of the floor surface. CONCLUSION: Based on the recognition error of the LDA, the recognition rate decreases when the model has a similar pattern. Therefore, to obtain the accurate 3D data, the difference of each class needs to be provided when developing a standardized model.
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BACKGROUND: Plant extracts contain a huge variety of pharmacologically active substances. Conventionally, various chromatographic methods must be applied several times to purify functional compounds to measure their functional activity. However, conventional purification methods are time-consuming and expensive due to the laborious purification process. Recently, a high-throughput discovery method that replaces such time-consuming purification processes was introduced; this method uses 15 T ultra-high-resolution Fourier transform ion cyclotron resonance mass spectrometry (15 T FT-ICR MS) and a high-throughput screening method. This 15 T FT-ICR MS provides unparalleled resolution and sub-ppm accuracy in mass measurements, while simultaneously detecting multiple compounds without separation. The high-throughput, simultaneous multi-component discovery method known as Scaling of Correlations between Activity and Mass Profiles (SCAMP) was used to detect functional compounds in a plant extract. We validated the performance of SCAMP using 33 fractions from antioxidant-rich mulberry ethyl acetate extract and known standard antioxidants. RESULTS: The mulberry fruit was first separated into 33 fractions by LC and analyzed using high-resolution mass spectrometry. The antioxidative strength of the 33 fractions and standard antioxidants was measured. To validate the efficiency of this antioxidant discovery method, correlations between the antioxidation activity profile and changes in mass intensity of components within the 33 fractions were calculated to provide relative scores for the antioxidant candidate list. Enrichment curves and area under the curve (AUC) values were then calculated to compare the performance of the methods. Using this improved scoring method, five strong antioxidants, chlorogenic acid (14.2 ng), dihydoxy quercetin (46.2 ng), rutin (154.0 ng), quercetin (71.7 ng) and luteolin (3.5 ng) in 2 kg mulberry fruit, were found within the top 20 candidates. CONCLUSIONS: We calculated AUCs in order to compare scoring methods quantitatively. Scoring systems were compared and calculated AUCs, where the AUCs for new scoring systems (0.98 and 0.99) were higher than the previously used correlation coefficient (AUC = 0.89). Using the new scoring algorithms, we successfully enriched thirteen unknown strong antioxidant candidates in addition to known antioxidants, methyl syringin and naringenin (3.5 ng) in mulberry extract. Targeted purification of these unknown candidates will significantly reduce purification time and labor.
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Guggulsterone (GS), a plant steroid and a compound found at high levels in Commiphora myrrha, exhibits anti-inflammatory, anti-cancer, and cholesterol-lowering effects. However, the potential of GS to ameliorate acute pancreatitis (AP) is unknown. The aim of this study was to evaluate the effects of GS on cerulein-induced AP. AP was induced by intraperitoneally injecting supramaximal concentrations of the stable cholecystokinin analog cerulein (50 µg/kg) hourly for 6 h. In the GS-treated group, GS was administered intraperitoneally (10, 25, or 50mg/kg) 1 h before the first cerulein injection. Mice were sacrificed 6 h after the final cerulein injection. Blood samples were collected to measure serum lipase levels and evaluate cytokine production. The pancreas and lung were rapidly removed for morphologic and histological examinations, flow cytometry analysis, myeloperoxidase (MPO) assay, and real-time reverse transcription-polymerase chain reaction analysis. Pre-treatment with GS attenuated cerulein-induced histological damage, reduced pancreas weight/body weight ratio, decreased serum lipase levels, inhibited infiltrations of macrophages and neutrophils, and suppressed cytokine production. Additionally, GS treatment suppressed the activation of extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) in the pancreas in cerulein-induced pancreatitis. In conclusion, our results suggest that GS attenuates AP via deactivation of ERK and JNK.
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Antiinflamatorios/uso terapéutico , Ceruletida/farmacología , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Pancreatitis/tratamiento farmacológico , Pregnenodionas/uso terapéutico , Enfermedad Aguda , Animales , Antiinflamatorios/administración & dosificación , Western Blotting , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Femenino , Inyecciones Intraperitoneales , Lipasa/sangre , Ratones Endogámicos C57BL , Páncreas/efectos de los fármacos , Páncreas/inmunología , Páncreas/patología , Pancreatitis/enzimología , Pancreatitis/inmunología , Pregnenodionas/administración & dosificaciónRESUMEN
OBJECTIVE: To evaluate the therapeutic effect of a Tibia Counter Rotator (TCR) with toe-out gait plate (GP) upon tibial internal torsion by a comparative analysis of transmalleolar angle (TMA) and gait analysis with GP alone. METHODS: Twenty participants with tibial internal torsion were recruited for this study. Each 10 participants were included in group A with TCR and GP application and in group B with GP application only. The TMA and the kinematic results were used for the evaluation of the therapeutic effects of orthoses. RESULTS: Within each group, TMA showed a significant increase after treatment. Group A showed a continuous improvement up to six months, however, group B showed an improvement up to five months only. Group A showed a significantly higher correction effect than group B after treatment. Regarding kinematic data, both groups showed a significantly decreased mean ankle adduction angle after treatment. However, group A showed a significantly lower mean ankle adduction angle than group B after six months. CONCLUSION: The group with TCR and GP showed a significantly better outcome and continued correction force compared to the group with GP only. Our results suggest that TCR with GP may be useful therapeutic orthoses for children with tibial internal torsion.
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OBJECTIVES: The lateral corticospinal tract (CST) is one of the most important neuronal pathways that mediate voluntary movements in the human brain. However, little is known about the role of the lateral CST on the gait. We attempted to investigate differences in gait pattern using a motion analysis system according to the integrity of the contralateral CST, which was classified using diffusion tensor tractography (DTT) in chronic hemiparetic stroke patients. METHODS: We recruited 16 chronic hemiparetic stroke patients and 12 normal subjects for this study. DTT findings of the CST for patients were classified into two groups: group A (eight patients); the integrity of the CST was preserved, group B (eight patients) - the CST was discontinued at or below the stroke lesion. We compared variables of gait between group A, group B, and normal controls using the motion analysis system. RESULTS: Group A and the control group showed a significantly higher peak angle for ankle dorsiflexion, knee internal rotation, and hip flexion, compared with group B (p < 0.05). On the other hand, the peak angle for ankle plantarflexion/external rotation, knee flexion/abduction, and hip extension of group A and group B were significantly lower than those of the control group (p < 0.05). CONCLUSION: We found that severe injury of the contralateral CST caused decreased movement of ankle dorsiflexion, knee internal rotation, and hip flexion in chronic hemiparetic stroke patients. As a result, the circumduction and abduction gait pattern in stroke patients is closely associated with severe injury of the contralateral CST.
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Trastornos Neurológicos de la Marcha/fisiopatología , Marcha/fisiología , Paresia/fisiopatología , Tractos Piramidales/fisiopatología , Accidente Cerebrovascular/fisiopatología , Adulto , Anciano , Análisis de Varianza , Articulación del Tobillo , Estudios de Casos y Controles , Enfermedad Crónica , Imagen de Difusión Tensora/métodos , Femenino , Cadera/fisiopatología , Humanos , Procesamiento de Imagen Asistido por Computador , Articulación de la Rodilla/fisiopatología , Masculino , Persona de Mediana Edad , Paresia/etiología , Rango del Movimiento Articular , Accidente Cerebrovascular/complicacionesRESUMEN
OBJECTIVE: The ankle foot orthosis (AFO) has been used for control of ankle motion in stroke patients for a long time. However, studies on the materials used in construction of AFOs have been limited. In this study, the authors attempted to investigate the effect of a hybrid AFO made with polypropylene and fabric in comparison with a conventional plastic AFO in terms of convenience and effect in patients with chronic hemiparetic stroke. DESIGN: Seventeen patients with chronic hemiparetic stroke who have used plastic AFOs were recruited for this study. Two types of AFOs were used: plastic AFO made with polypropylene and hybrid AFO made with polypropylene covered with canvas fabric, which were individually molded and fitted. Convenience was evaluated using a self-developed questionnaire on patients' satisfaction and weights of AFO, and effect was evaluated using gait analysis. RESULTS: On the satisfaction questionnaire, satisfaction was greater for the hybrid AFO, and it was lighter in weight than the plastic AFO (P < 0.05). In gait analysis, faster walking speed, larger mean and peak ankle dorsiflexion angles, and ankle dorsiflexion angles at heel strike and toe off were observed for the hybrid and plastic AFOs compared with barefoot (P < 0.05). No significant difference was observed between the two orthoses, except for ankle dorsiflexion angle at heel strike, in which the plastic AFO showed higher ankle dorsiflexion angle than did the hybrid AFO. CONCLUSIONS: According to the results of this study, the hybrid AFO showed a similar effect in function, except for ankle dorsiflexion angle at heel strike, and was superior with regard to convenience compared with the conventional plastic AFO in chronic hemiparetic stroke patients. Therefore, it seems that, in general, the hybrid AFO can be recommended for hemiparetic stroke patients who require an AFO.
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Fibra de Algodón , Ortesis del Pié , Trastornos Neurológicos de la Marcha/rehabilitación , Hemiplejía/rehabilitación , Polipropilenos , Rehabilitación de Accidente Cerebrovascular , Adulto , Anciano , Articulación del Tobillo/fisiología , Diseño de Equipo , Femenino , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/fisiopatología , Hemiplejía/complicaciones , Hemiplejía/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Rango del Movimiento Articular , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/fisiopatologíaRESUMEN
BACKGROUND: Plant extracts are a reservoir of pharmacologically active substances; however, conventional analytical methods can analyze only a small portion of an extract. Here, we report a high-throughput analytical method capable of determining most phytochemicals in a plant extract and of providing their molecular formulae from a single experiment using ultra-high-resolution electrospray ionization mass spectrometry (UHR ESI MS). UHR mass profiling was used to analyze natural compounds in a 70% ethanol ginseng extract, which was directly infused into a 15 T Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer for less than 10 min without a separation process. RESULTS: The UHR FT-ICR MS yielded a mass accuracy of 0.5 ppm and a mass resolving power (m/Δm) of 1,000,000-270,000 for the range m/z 290-1,100. The mass resolution was sufficient to resolve the isotopic fine structure (IFS) of many compounds in the extract. After noise removal from 1,552 peaks, 405 compounds were detected. The molecular formulae of 123 compounds, including 33 ginsenosides, were determined using the observed IFS, exact monoisotopic mass, and exact mass difference. Liquid chromatography (LC)/FT-ICR MS of the extract was performed to compare the high-throughput performance of UHR ESI FT-ICR MS. The LC/FT-ICR MS detected only 129 compounds, including 19 ginsenosides. The result showed that UHR ESI FT-ICR MS identified three times more compounds than LC/FT-ICR MS and in a relatively shorter time. The molecular formula determination by UHR FT-ICR MS was validated by LC and tandem MS analyses of three known ginsenosides. CONCLUSIONS: UHR mass profiling of a plant extract by 15 T FT-ICR MS showed that multiple compounds were simultaneously detected and their molecular formulae were decisively determined by a single experiment with ultra-high mass resolution and mass accuracy. Simultaneous molecular determination of multiple natural products by UHR ESI FT-ICR MS would be a powerful method to profile a wide range of natural compounds.
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AIM: To determine if the fraction of Nardostachys jatamansi (NJ) has the potential to ameliorate the severity of acute pancreatitis (AP). METHODS: Mice were administered the biologically active fraction of NJ, i.e., the 4th fraction (NJ4), intraperitoneally, and then injected with the stable cholecystokinin analogue cerulein hourly for 6 h. Six hours after the last cerulein injection, the pancreas, lung, and blood were harvested for morphological examination, measurement of cytokine expression, and examination of neutrophil infiltration. RESULTS: NJ4 administration attenuated the severity of AP and lung injury associated with AP. It also reduced cytokine production and neutrophil infiltration and resulted in the in vivo up-regulation of heme oxygenase-1 (HO-1). Furthermore, NJ4 and its biologically active fraction, NJ4-2 inhibited the cerulein-induced death of acinar cells by inducing HO-1 in isolated pancreatic acinar cells. CONCLUSION: These results suggest that NJ4 may be a candidate fraction offering protection in AP and NJ4 might ameliorate the severity of pancreatitis by inducing HO-1 expression.
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Ceruletida , Nardostachys , Páncreas/efectos de los fármacos , Pancreatitis/prevención & control , Extractos Vegetales/farmacología , Enfermedad Aguda , Animales , Muerte Celular/efectos de los fármacos , Citocinas/metabolismo , Citoprotección , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Enzimas/sangre , Femenino , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Mediadores de Inflamación/metabolismo , Pulmón/efectos de los fármacos , Pulmón/patología , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Nardostachys/química , Infiltración Neutrófila/efectos de los fármacos , Páncreas/metabolismo , Páncreas/patología , Pancreatitis/inducido químicamente , Pancreatitis/genética , Pancreatitis/metabolismo , Pancreatitis/patología , Raíces de Plantas , Índice de Severidad de la Enfermedad , Factores de Tiempo , Regulación hacia ArribaRESUMEN
Solubility of curcumin at physiological pH was significantly increased by forming solid dispersion (SD) with Solutol® HS15. Since curcumin undergoes hydrolytic degradation, chemical stability study was conducted in pH 1.2, 6.8 and 7.4 buffer media. Solutol® HS15 exhibited superior stabilizing effect to Cremophor® RH40 and Kollidon® 30. The physical state of the dispersed curcumin in the polymer matrix was characterized by differential scanning calorimetry and X-ray diffraction studies. SD preparation transformed curcumin into amorphous form and facilitated micellar incorporation, thereby preventing hydrolysis in aqueous medium. In vitro drug release in pH 6.8 buffer revealed that SD (1:10) improved the dissolution of curcumin with approximately 90% release of the drug within 1h. Pharmacokinetic study of the solid dispersion formulation in rat showed that bioavailability of the drug was significantly improved as compared to pure curcumin. SD containing 1:10 ratio of drug and Solutol® HS15 resulted in approximately 5 fold higher AUC(0-12h). SD formulation was physically stable over the study period of 3 months.
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Curcumina/química , Portadores de Fármacos/química , Polietilenglicoles/química , Ácidos Esteáricos/química , Animales , Disponibilidad Biológica , Curcumina/farmacocinética , Portadores de Fármacos/farmacocinética , Estabilidad de Medicamentos , Masculino , Polietilenglicoles/farmacocinética , Difracción de Polvo , Ratas , Ratas Sprague-Dawley , Solubilidad , Ácidos Esteáricos/farmacocinética , Difracción de Rayos XRESUMEN
Myrrh has been used as an antibacterial and anti-inflammatory agent. However, effect of myrrh on peritoneal macrophages and clinically relevant models of septic shock, such as cecal ligation and puncture (CLP), is not well understood. Here, we investigated the inhibitory effect and mechanism(s) of myrrh on inflammatory responses. Myrrh inhibited LPS-induced productions of inflammatory mediators such as nitric oxide, prostaglandin E(2), and tumor necrosis factor-α but not of interleukin (IL)-1ß and IL-6 in peritoneal macrophages. In addition, Myrrh inhibited LPS-induced activation of c-jun NH(2)-terminal kinase (JNK) but not of extracellular signal-regulated kinase (ERK), p38, and nuclear factor-κB. Administration of Myrrh reduced the CLP-induced mortality and bacterial counts and inhibited inflammatory mediators. Furthermore, administration of Myrrh attenuated CLP-induced liver damages, which were mainly evidenced by decreased infiltration of leukocytes and aspartate aminotransferase/alanine aminotransferase level. Taken together, these results provide the evidence for the anti-inflammatory and antibacterial potential of Myrrh in sepsis.
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The major compound of bee venom, melittin, has been used as an anti-inflammatory reagent for decades. However, the potential of melittin to ameliorate acute pancreatitis (AP) is unknown. Our aim was to investigate the effect of melittin on cerulein-induced AP. Pre- and post-treatment with melittin inhibited histological changes in the pancreas and lungs during cerulein-induced AP. Pancreatic weight/body weight ratios; digestive enzymes, including amylase and lipase; serum and pancreatic cytokine expression; and myeloperoxidase activity were decreased. In addition, treatment with melittin inhibited the activation of c-Jun NH(2)-terminal protein kinase (JNK) in the pancreas during cerulein-induced pancreatitis. In accordance with the results of in vivo experiments, melittin reduced cerulein-induced cell death, and production of inflammatory cytokines. In conclusion, our results suggest that melittin attenuated AP and AP-associated lung injury through the inhibition of JNK activation.
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Antiinflamatorios no Esteroideos/uso terapéutico , Ceruletida/antagonistas & inhibidores , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Meliteno/uso terapéutico , Pancreatitis Aguda Necrotizante/tratamiento farmacológico , Amilasas/sangre , Animales , Muerte Celular/efectos de los fármacos , Ceruletida/administración & dosificación , Citocinas/biosíntesis , Citocinas/sangre , Femenino , Lipasa/sangre , Pulmón/efectos de los fármacos , Pulmón/enzimología , Pulmón/fisiopatología , Ratones , Ratones Endogámicos C57BL , Pancreatitis Aguda Necrotizante/inducido químicamente , Pancreatitis Aguda Necrotizante/enzimología , Pancreatitis Aguda Necrotizante/patología , Peroxidasa/sangre , Resultado del TratamientoRESUMEN
Acute pancreatitis (AP) is an inflammatory disease involving acinar cell injury and rapid production and release of inflammatory cytokines, which play a dominant role in local pancreatic inflammation and systemic complications. 2',4',6'-Tris (methoxymethoxy) chalcone (TMMC), a synthetic chalcone derivative, displays potent anti-inflammatory effects. Therefore, we aimed to investigate whether TMMC might affect the severity of AP and pancreatitis-associated lung injury in mice. We used the cerulein hyperstimulation model of AP. Severity of pancreatitis was determined in cerulein-injected mice by histological analysis and neutrophil sequestration. The pretreatment of mice with TMMC reduced the severity of AP and pancreatitis-associated lung injury and inhibited several biochemical parameters (activity of amylase, lipase, trypsin, trypsinogen, and myeloperoxidase and production of proinflammatory cytokines). In addition, TMMC inhibited pancreatic acinar cell death and production of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 by inhibiting NF-κB and extracellular signal-regulated protein kinase 1/2 (ERK1/2) activation. Neutralizing antibodies for TNF-α, IL-1ß, and IL-6 inhibited cerulein-induced cell death in isolated pancreatic acinar cells. Moreover, pharmacological blockade of NF-κB/ERK1/2 reduced acinar cell death and production of TNF-α, IL-1ß, and IL-6 in isolated pancreatic acinar cells. In addition, posttreatment of mice with TMMC showed reduced severity of AP and lung injury. Our results suggest that TMMC may reduce the complications associated with pancreatitis.
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Antiinflamatorios/uso terapéutico , Chalconas/uso terapéutico , Lesión Pulmonar/prevención & control , Pancreatitis/tratamiento farmacológico , Amilasas/sangre , Animales , Ceruletida , Interleucina-1beta/sangre , Interleucina-6/sangre , Lipasa/sangre , Ratones , Ratones Endogámicos C57BL , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Pancreatitis/inducido químicamente , Pancreatitis/complicaciones , Pancreatitis/patología , Peroxidasa/metabolismo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Curcuma longa (CL) has been reported to possess a variety of pharmacological activities. However, the effects of CL on acute pancreatitis (AP) have not yet been determined. To this end, we examined the effects of CL on cerulein-induced AP. Cell viability and cytokine productions were measured in pancreatic acini. Mice were divided into 3 groups: i) Normal group, ii) normal saline-treated group, iii) group treated with CL at a dose of 0.05, 0.1, 0.5 and 1 g/kg. CL was administered orally to mice for 7 days. The mice were intraperitoneally injected with the stable cholecystokinin analogue, cerulein (50 µg/kg), every hour for a total of 6 h. The mice were sacrificed 6 h after the completion of the cerulein injections. Blood samples were obtained to determine serum amylase, lipase and cytokine levels. The pancreas was rapidly removed for morphological examination, measurement of tissue myeloperoxidase activity, as well as the level of cytokines and heme oxygenase-1 (HO-1). The CL treatment reduced cerulein-induced cell death and cytokine production in pancreatic acini. The administration of CL significantly ameliorated the severity of pancreatitis and pancreatitis-associated lung injury, as was shown by the reduction in pancreatic edema, neutrophil infiltration, vacuolization, necrosis, serum amylase, lipase and cytokine levels, and mRNA expression of multiple inflammatory mediators such as interleukin (IL)-1ß and -6 and tumor necrosis factor (TNF)-α. In order to identify the regulatory mechanism of CL on cerulein-induced pancreatitis, we examined the level of HO-1 in the pancreas. We found that the administration of CL induced HO-1. Our results suggest that CL plays a protective role in the development of AP and pancreatitis-associated lung injury.
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Ceruletida/farmacología , Curcuma/química , Lesión Pulmonar/tratamiento farmacológico , Pancreatitis/inducido químicamente , Pancreatitis/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Enfermedad Aguda , Animales , Citocinas/genética , Citocinas/metabolismo , Femenino , Hemo-Oxigenasa 1/metabolismo , Lesión Pulmonar/etiología , Lesión Pulmonar/patología , Ratones , Ratones Endogámicos C57BL , Páncreas/citología , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Páncreas/patología , Pancreatitis/complicaciones , Peroxidasa/metabolismoRESUMEN
Nardostachys jatamansi (NJ) has been used in the treatment of inflammatory diseases. However, it is not clear how NJ produces anti-inflammatory effects. In the present study, using an experimental model of lipopolysaccharide (LPS)-induced endotoxin shock, the protective effects and mechanisms of action of NJ were investigated. The water extract of roots of NJ was administrated to mice orally (1, 5, and 10 mg/kg) 1 h after or before LPS challenge. The administration of NJ inhibited LPS-induced endotoxin shock and the production of inflammatory mediators, such as interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-α/ß. Murine peritoneal macrophages were used to determine the production of inflammatory mediators. In peritoneal macrophages, NJ also inhibited LPS-induced production of inflammatory mediators, such as IL-1ß, IL-6, TNF-α, and IFN-α/ß. In addition, NJ reduced the activation of mitogen-activated protein kinases (MAPKs) and the level of expression of interferon regulatory factor (IRF)-1 and IRF-7 mRNA. Furthermore, post-treatment with NJ reduced LPS-induced endotoxin shock and the production of inflammatory mediators. These results suggest that NJ inhibits endotoxin shock by inhibiting the production of IL-1ß, IL-6, TNF-α, and IFN-α/ß through the inhibition of MAPKs activation and IRF induction.
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Lipopolisacáridos/toxicidad , Nardostachys/química , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Raíces de Plantas/química , Choque Séptico/tratamiento farmacológico , Animales , Western Blotting , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Femenino , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Ratones , Ratones Endogámicos C57BL , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Piperine, a main component of Piper longum Linn. and Piper nigrum Linn., is a plant alkaloid with a long history of medical use. Piperine exhibits anti-inflammatory activity; however, the underlying mechanism remains unknown. We examined the effects of piperine on lipopolysaccharide (LPS)-induced inflammatory responses. Administration of piperine inhibited LPS-induced endotoxin shock, leukocyte accumulation and the production of tumor necrosis factor-alpha (TNF-alpha), but not of interleukin (IL)-1beta and IL-6. In peritoneal macrophages, piperine inhibited LPS/poly (I:C)/CpG-ODN-induced TNF-alpha production. Piperine also inhibited LPS-induced endotoxin shock in TNF-alpha knockout (KO) mice. To clarify the inhibitory mechanism of LPS-induced endotoxin shock, type 1 interferon (IFN) mRNA expression was determined. Piperine inhibited LPS-induced expression of type 1 IFN mRNA. Piperine inhibited the levels of interferon regulatory factor (IRF)-1 and IRF-7 mRNA, and the phosphorylation and nuclear translocation of IRF-3. Piperine also reduced activation of signal transducer and activator of transcription (STAT)-1. In addition, activation of STAT-1 was inhibited in IFN-alpha/beta-treated cells by piperine. These results suggest that piperine inhibits LPS-induced endotoxin shock through inhibition of type 1 IFN production.
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Alcaloides/farmacología , Benzodioxoles/farmacología , Inflamación/tratamiento farmacológico , Lipopolisacáridos/farmacología , Piperidinas/farmacología , Alcamidas Poliinsaturadas/farmacología , Alcaloides/uso terapéutico , Animales , Benzodioxoles/uso terapéutico , Femenino , Técnicas de Inactivación de Genes , Inflamación/inmunología , Inflamación/metabolismo , Interferón Tipo I/biosíntesis , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Ratones , Ratones Endogámicos C57BL , Piperidinas/uso terapéutico , Alcamidas Poliinsaturadas/uso terapéutico , Factor de Transcripción STAT1/metabolismo , Choque Séptico/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/deficiencia , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Glycogen synthase kinase-3 (GSK-3) plays an important role in the regulation of apoptosis. However, the role of GSK-3 in the auditory system remains unknown. Here we examined whether the GSK-3-specific inhibitors, SB 216763 and LiCl, could protect against cisplatin-induced cytotoxicity of auditory cells. GSK-3 was activated by cisplatin treatment of HEI-OC1 cells. SB 216763 or LiCl treatments inhibited cisplatin-induced apoptosis in a dose-dependent manner and activated caspase-9, -8 and -3. In rat primary explants of the organ of Corti, SB 216763 or LiCl treatments completely abrogated the cisplatin-induced destruction of outer hair cell arrays. Administration of SB 216763 or LiCl inhibited cochlear destruction and the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-6 in cisplatin-injected mice. Furthermore, administration of SB 216763 or LiCl reduced the thresholds of the auditory brainstem response (ABR) in cisplatin-injected mice. Collectively, these results suggest that cisplatin-induced ototoxicity might be associated with modulation of GSK-3 activation.
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Antineoplásicos/toxicidad , Cisplatino/toxicidad , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Pérdida Auditiva/prevención & control , Indoles/farmacología , Cloruro de Litio/farmacología , Maleimidas/farmacología , Órgano Espiral/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Estimulación Acústica , Animales , Antineoplásicos/administración & dosificación , Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Línea Celular , Cisplatino/administración & dosificación , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Activación Enzimática , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Células Ciliadas Auditivas/efectos de los fármacos , Células Ciliadas Auditivas/enzimología , Pérdida Auditiva/inducido químicamente , Pérdida Auditiva/enzimología , Pérdida Auditiva/patología , Pérdida Auditiva/fisiopatología , Indoles/administración & dosificación , Inyecciones Intraperitoneales , Interleucina-1beta/sangre , Interleucina-6/sangre , Cloruro de Litio/administración & dosificación , Maleimidas/administración & dosificación , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Técnicas de Cultivo de Órganos , Órgano Espiral/enzimología , Órgano Espiral/patología , Órgano Espiral/fisiopatología , Fosforilación , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Uncariae rhynchophylla (UR) is an herb which has blood pressure lowering and anti-inflammatory effects and has been prescribed traditionally to treat stroke and vascular dementia. AIM OF STUDY: In the present study, we examined whether UR suppress Atopic dermatitis (AD)-like skin lesions in NC/Nga mice treated with 2, 4-dinitrofluorobenzene (DNFB) under SPF conditions. MATERIAL AND METHODS: The effect of UR in DNFB- treated NC/Nga mice was determined by measuring the skin symptom severity, levels of serum IgE, and of the amounts of IL-4 and IFN-gamma secreted by activated T cells in draining lymph nodes. RESULTS: Oral administration of UR to DNFB-treated NC/Nga mice was found to inhibit ear thickness increases and the skin lesions induced by DNFB. IFN-gamma production by CD4+ T cells from the lymph nodes of DNFB-treated NC/Nga mice was significantly inhibited by UR treatment, although levels of IL-4 and total IgE in serum were not. CONCLUSION: UR may suppress the development of AD-like dermatitis in DNFB-treated NC/Nga mice by reducing IFN-gamma production.
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Antiinflamatorios/uso terapéutico , Dermatitis Atópica/prevención & control , Interferón gamma/metabolismo , Fitoterapia , Extractos Vegetales/uso terapéutico , Piel/efectos de los fármacos , Uncaria , Administración Oral , Animales , Antiinflamatorios/farmacología , Linfocitos T CD4-Positivos/metabolismo , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/metabolismo , Dermatitis Atópica/patología , Dinitrofluorobenceno , Regulación hacia Abajo/efectos de los fármacos , Femenino , Inmunoglobulina E/sangre , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Interferón gamma/antagonistas & inhibidores , Interleucina-4/antagonistas & inhibidores , Ganglios Linfáticos/metabolismo , Ratones , Ratones Endogámicos , Extractos Vegetales/farmacología , Raíces de Plantas , Prednisolona/farmacología , Prednisolona/uso terapéutico , Piel/metabolismo , Piel/patología , Células TH1/metabolismo , Células Th2/metabolismoRESUMEN
AIM: To investigate the effect of Gardenia jasminoides (GJ) on cerulein-induced acute pancreatitis (AP) in mice. METHODS: C57BL/6 mice weighing 18-20 g were divided into three groups. (1) Normal saline-treated group, (2) treatment with GJ at a dose of 0.1 g/kg, (3) treatment with GJ at a dose of 1 g/kg. GJ was administered orally (n = 6 per group) for 1 wk. Three hours later, the mice were given an intraperitoneal injection of cerulein (50 microg/kg), a stable cholecystokinin (CCK) analogue, every hour for a total of 6 h as described previously. The mice were sacrificed at 6 h after completion of cerulein injections. Blood samples were obtained to determine serum amylase, lipase and cytokine levels. The pancreas was rapidly removed for morphologic examination and scoring. A portion of pancreas was stored at -70 degree and prepared for the measurement of tissue myeloperoxidase (MPO) activity, an indicator of neutrophil sequestration, and for reverse-transcriptase PCR (RT-PCR) and real-time PCR measurements. RESULTS: Treatment with GJ decreased significantly the severity of pancreatitis and pancreatitis-associated lung injury. Treatment with GJ attenuated the severity of AP compared with saline-treated mice, as shown by reduction in pancreatic edema, neutrophil infiltration, serum amylase and lipase levels, serum cytokine levels, and mRNA expression of multiple inflammatory mediators. CONCLUSION: These results suggest that GJ attenuated the severity of AP as well as pancreatitis-associated lung injury.
Asunto(s)
Antiinflamatorios/farmacología , Gardenia , Lesión Pulmonar/prevención & control , Pulmón/efectos de los fármacos , Páncreas/efectos de los fármacos , Pancreatitis/prevención & control , Enfermedad Aguda , Administración Oral , Amilasas/sangre , Animales , Antiinflamatorios/administración & dosificación , Peso Corporal , Ceruletida , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Mediadores de Inflamación/sangre , Interleucina-1beta/sangre , Interleucina-6/sangre , Lipasa/sangre , Pulmón/inmunología , Pulmón/patología , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/inmunología , Ratones , Ratones Endogámicos C57BL , Infiltración Neutrófila/efectos de los fármacos , Tamaño de los Órganos , Páncreas/inmunología , Páncreas/patología , Pancreatitis/inducido químicamente , Pancreatitis/inmunología , Peroxidasa/metabolismo , Extractos Vegetales/farmacología , ARN Mensajero/metabolismo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
This study was conducted to investigate the effects of mechanical stress, particularly cyclic strain, on proinflammatory cytokines as well as antioxidant properties and their interactions with cellular defense systems in human dental pulp (HDP) cells. Exposure of HDP cells to mechanical strain induced inflammatory cytokines such as interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6, as well as antioxidant genes such as heme oxygenase-1, superoxide dismutases, reduced nicotinamide adenine dinucleotide phosphate quinone oxidoreductase-1, and glutathione peroxidases. In addition, treatment with N-acetylcysteine, indomethacin, and heme oxygenase-1 inhibitors blocked reactive oxygen species production, antioxidant response element (ARE) gene expression, and Nrf2 accumulation that occurred in response to mechanical stress. These data demonstrate that mechanical strain activates inflammatory cytokines and oxidative stress, which then act in concert to induce the Nrf2-/ARE-mediated antioxidant enzymes. Therefore, we suggest that the activation of a compensatory adaptation or defense antioxidant system might represent a novel mechanism for protecting HDP cells against mechanical stress.