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BACKGROUND: Anemia is associated with adverse outcomes and prolonged hospitalizations in critically ill patients. Regarding the recent adoption of restrictive transfusion protocols in intensive care unit (ICU) management, anemia remains highly prevalent even after ICU discharge. This study aimed to investigate the prevalence of anemia following ICU discharge and factors affecting recovery from anemia. METHODS: In this retrospective cohort study involving 3969 adult ICU survivors, we assessed anemia severity using the National Cancer Institute criteria at six time points: ICU admission, ICU discharge, hospital discharge, and at 3-, 6-, and 12-month post-hospital discharge. In addition, baseline characteristics, including age, sex, comorbidities, and recent iron supplementation or erythropoietin administration, were evaluated. RESULTS: Our findings revealed an in-hospital mortality rate of 28.6%. The median hospital and ICU stays were 20 and 5 days, respectively, with common comorbidities including hypertension, and diabetes mellitus (DM). Among the patients, the hemoglobin levels of 3967 patients were confirmed at the time of discharge from the ICU, representing 99.95% of the total. The prevalence of anemia persisted post- ICU discharge; less than 30% of patients recovered, whereas 13.6% of them experienced worsening of anemia post-ICU discharge. Factors contributing to anemia severity were female sex, DM, chronic renal failure, malignant solid tumors, and administration of iron supplements. CONCLUSIONS: This study highlighted the need for targeted interventions to manage anemia post-ICU discharge and suggested potential factors that influence recovery from anemia.
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Anemia , Cuidados Críticos , Humanos , Femenino , Masculino , Anemia/epidemiología , Anemia/terapia , Estudios Retrospectivos , Persona de Mediana Edad , Prevalencia , Anciano , Cuidados Críticos/métodos , Unidades de Cuidados Intensivos , AdultoRESUMEN
Arecae pericarpium (AP), the fruit peel of the betel palm, is a traditional Oriental herbal medicine. AP is used to treat various diseases and conditions, such as ascites, edema, and urinary retention, in traditional Korean medicine. Recent studies have demonstrated its anti-obesity and antibacterial effects; however, its anti-neuroinflammatory effects have not yet been reported. Therefore, we investigated the anti-neuroinflammatory effects of AP on lipopolysaccharide (LPS)-stimulated mouse microglia in this study. To determine the anti-neuroinflammatory effects of AP on BV2 microglial cells, we examined the production of nitric oxide (NO) using Griess assay and assessed the mRNA expression levels of inflammatory mediators, such as inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, and pro-inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α, using a real-time reverse transcription-polymerase chain reaction. Furthermore, we determined the levels of mitogen-activated protein kinases and IκBα via Western blotting to understand the regulating mechanisms of AP. AP treatment decreased NO production in LPS-stimulated BV2 cells. Additionally, AP suppressed the expression of iNOS and COX-2 and the production of pro-inflammatory cytokines. AP also inhibited the activation of p38 and nuclear factor-kappa B (NF-κB) in LPS-stimulated BV2 cells. Therefore, AP exerts anti-neuroinflammatory effects via inactivation of the p38 and NF-κB pathways.
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Nardostachys spp. have been widely used in Asia as a folk medicine. In particular, the extracts of Nardostachys jatamansi, a species that grows in China, India, and Tibet, have been used to treat mental disorders, hyperlipidemia, hypertension, and convulsions. In this investigation, the potential of 20% aqueous ethanol extract of N. jatamansi (NJ20) as a botanical drug was explored by chemically investigating its constituents and its anti-neuroinflammatory effects on lipopolysaccharide- (LPS-) induced in vitro and in vivo models. Nine secondary metabolites were isolated and identified from NJ20, and quantitative analysis of these metabolites revealed desoxo-narchinol A as the major constituent. In LPS-challenged cells, pretreatment with NJ20 inhibited the LPS-induced excessive production of proinflammatory mediators, such as nitric oxide, prostaglandin E2, interleukin- (IL-) 1ß, IL-6, and tumor necrosis factor-α. NJ20 also attenuated the overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2. Additionally, pre-intraperitoneal injection of NJ20 downregulated the mRNA overexpression of IL-1ß, IL-6, and iNOS in the prefrontal cortex, hypothalamus, and hippocampus of the LPS-stimulated C57BL/c mouse model. Chemical and biological investigations of NJ20 revealed that it is a potential inhibitor of LPS-induced neuroinflammatory responses in microglial cells and mouse models. The major active constituent of NJ20, desoxo-narchinol A, demonstrated anti-neuroinflammatory effects. Hence, our findings indicate that NJ20 may be a promising herbal mixture for developing a functional product and/or herbal drug for treating neuroinflammatory diseases.
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Our previous report revealed that Gardenia jasminoides (GJ) has protective effects against acute pancreatitis. So, we examined whether aqueous extract of GJ has anti-inflammation and antifibrotic effects even against cerulein-induced chronic pancreatitis (CP). CP was induced in mice by an intraperitoneal injection of a stable cholecystokinin (CCK) analogue, cerulein, six times a day, four days per week for three weeks. GJ extract (0.1 or 1[Formula: see text]g/kg) or saline (control group) were intraperitoneally injected 1[Formula: see text]h before first cerulein injection. After three weeks of stimulation, the pancreas was harvested for the examination of several fibrotic parameters. In addition, pancreatic stellate cells (PSCs) were isolated using gradient methods to examine the antifibrogenic effects of GJ. In the cerulein-induced CP mice, the histological features of the pancreas showed severe tissue damage such as enlarged interstitial spaces, inflammatory cell infiltrate and glandular atrophy, and tissue fibrosis. However, treatment of GJ reduced the severity of CP such as pancreatic edema and inflammatory cell infiltration. Furthermore, treatment of GJ increased pancreatic acinar cell survival, and reduced pancreatic fibrosis and activation of PSC in vivo and in vitro. In addition, GJ treatment inhibited the activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) in the PSCs. These results suggest that GJ attenuated the severity of CP and the pancreatic fibrosis by inhibiting JNK and ERK activation during CP.
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Ceruletida/efectos adversos , Gardenia/química , Pancreatitis Crónica/tratamiento farmacológico , Pancreatitis Crónica/prevención & control , Fitoterapia , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Animales , Modelos Animales de Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Fibrosis , Inyecciones Intraperitoneales , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Masculino , Ratones Endogámicos C57BL , Páncreas/patología , Células Estrelladas Pancreáticas/patología , Pancreatitis Crónica/inducido químicamente , Pancreatitis Crónica/patología , Extractos Vegetales/aislamiento & purificaciónRESUMEN
Ginsenosides are known to have various highly pharmacological activities, such as anti-cancer and anti-inflammatory effects. However, the search for the most effective ginsenosides against the pathogenesis of atopic dermatitis (AD) and the study of the effects of ginsenosides on specific cytokines involved in AD remain unclear. In this study, ginsenoside Rh2 was shown to exert the most effective anti-inflammatory action on thymic stromal lymphopoietin (TSLP) and interleukin 8 in tumor necrosis factor-alpha and polyinosinic: polycytidylic acid induced normal human keratinocytes by inhibiting proinflammatory cytokines at both protein and transcriptional levels. Concomitantly, Rh2 also efficiently alleviated 2,4-dinitrochlorobenzene-induced AD-like skin symptoms when applied topically, including suppression of immune cell infiltration, cytokine expression, and serum immunoglobulin E levels in NC/Nga mice. In line with the in vitro results, Rh2 inhibited TSLP levels in AD mice via regulation of an underlying mechanism involving the nuclear factor κB pathways. In addition, in regard to immune cells, we showed that Rh2 suppressed not only the expression of TSLP but the differentiation of naïve CD4+ T-cells into T helper type 2 cells and their effector function in vitro. Collectively, our results indicated that Rh2 might be considered as a good therapeutic candidate for the alternative treatment of AD.
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Citocinas/metabolismo , Dermatitis Atópica/tratamiento farmacológico , Ginsenósidos/uso terapéutico , FN-kappa B/metabolismo , Células Th2/metabolismo , Animales , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/metabolismo , Diferenciación Celular/efectos de los fármacos , Línea Celular , Citocinas/análisis , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/patología , Dinitroclorobenceno/toxicidad , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Ginsenósidos/farmacología , Humanos , Inmunoglobulina E/sangre , Masculino , Ratones , Piel/metabolismo , Piel/patología , Células Th2/citología , Linfopoyetina del Estroma TímicoRESUMEN
Cutaneous wound healing is a well-orchestrated event in which many types of cells and growth factors are involved in restoring the barrier function of skin. In order to identify whether ginsenosides, the main active components of Panax ginseng, promote wound healing, the proliferation and migration activities of 15 different ginsenosides were tested by MTT assay and scratched wound closure assay. Among ginsenosides, gypenoside LXXV (G75) showed the most potent wound healing effects. Thus, this study aimed to investigate the effects of G75 on wound healing in vivo and characterize associated molecular changes. G75 significantly increased proliferation and migration of keratinocytes and fibroblasts, and promoted wound closure in an excision wound mouse model compared with madecassoside (MA), which has been used to treat wounds. Additionally, RNA sequencing data revealed G75-mediated significant upregulation of connective tissue growth factor (CTGF), which is known to be produced via the glucocorticoid receptor (GR) pathway. Consistently, the increase in production of CTGF was confirmed by western blot and ELISA. In addition, GR-competitive binding assay and GR translocation assay results demonstrated that G75 can be bound to GR and translocated into the nucleus. These results demonstrated that G75 is a newly identified effective component in wound healing.
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Antiinflamatorios/farmacología , Factor de Crecimiento del Tejido Conjuntivo/genética , Fármacos Dermatológicos/farmacología , Receptores de Glucocorticoides/genética , Herida Quirúrgica/tratamiento farmacológico , Cicatrización de Heridas/efectos de los fármacos , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Línea Celular , Movimiento Celular/efectos de los fármacos , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Fármacos Dermatológicos/química , Fármacos Dermatológicos/aislamiento & purificación , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Regulación de la Expresión Génica , Ginsenósidos/química , Ginsenósidos/aislamiento & purificación , Ginsenósidos/farmacología , Gynostemma/química , Humanos , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Panax/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Transporte de Proteínas , Receptores de Glucocorticoides/metabolismo , Transducción de Señal , Piel/efectos de los fármacos , Piel/lesiones , Piel/metabolismo , Herida Quirúrgica/genética , Herida Quirúrgica/metabolismo , Herida Quirúrgica/patología , Cicatrización de Heridas/fisiologíaRESUMEN
OBJECTIVES: We set out to examine whether berberine (BBR) might affect the severity of pancreatitis and pancreatitis-associated lung injury in choline-deficient ethionine-supplemented (CDE) diet-induced severe acute pancreatitis. METHODS: Severe acute pancreatitis was induced by feeding a CDE diet for 3 days. Berberine was administered intraperitoneally during CDE diet. Mice were killed on days 1, 2, and 3 after the onset of CDE diet. The severity of pancreatitis was assessed by evaluating changes to the pancreas and lung and survival rate. Blood, pancreas, and lung were harvested for further examination. Furthermore, the regulating mechanisms of BBR were evaluated on the pancreas. RESULTS: Administration of BBR significantly inhibited histological damage to the pancreas and lung and decreased serum level of amylase and lipase, myeloperoxidase activity, cytokine production, and the mortality rate. Furthermore, administration of BBR inhibited activation of nuclear factor kappa B, c-Jun N-terminal kinases, and p38 in the pancreas during CDE diet. CONCLUSIONS: These findings suggest that BBR attenuates the severity of pancreatitis by inhibiting activation of nuclear factor kappa B, c-Jun N-terminal kinase, and p38 and that BBR could be used as a beneficial agent to regulate AP.
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Berberina/farmacología , Lesión Pulmonar/prevención & control , Pulmón/efectos de los fármacos , Páncreas/efectos de los fármacos , Pancreatitis Aguda Necrotizante/prevención & control , Amilasas/sangre , Animales , Colina/aislamiento & purificación , Dieta/efectos adversos , Etionina/administración & dosificación , Femenino , Lipasa/sangre , Pulmón/metabolismo , Pulmón/patología , Lesión Pulmonar/mortalidad , Ratones Endogámicos C57BL , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Páncreas/metabolismo , Páncreas/patología , Pancreatitis Aguda Necrotizante/etiología , Pancreatitis Aguda Necrotizante/mortalidad , Fitoterapia/métodos , Tasa de SupervivenciaRESUMEN
Eclipta prostrata (EP) and its compounds are known to have several pharmacological effects including anti-inflammatory effects. In the present study, we demonstrated that EP improves the dextran sulfate sodium (DSS)-induced colitis symptoms such as body weight loss, colon length shortening and disease activity index. In DSS-induced colitis tissue, EP controls the protein expressions of cyclooxygenase-2 (COX-2) and hypoxia inducible factor-1[Formula: see text] (HIF-1[Formula: see text]). In addition, the release of prostaglandin E2 and vascular endothelial growth factor-A were significantly reduced by EP administration. EP also inhibited COX-2 and HIF-1[Formula: see text] expressions in the tumor necrosis factor-[Formula: see text] stimulated HT-29 cells. These inhibitory effects of EP occurred by reducing the phosphorylation of I[Formula: see text]B and the translocation of the nuclear factor-[Formula: see text]B (NF-[Formula: see text]B). Additionally, we found through HPLC analysis that wedelolactone, which is an inhibitor of NF-[Formula: see text]B transcription, was contained in water extract of EP. These results indicate that EP can improve colitis symptoms through the modulation of immune function in intestinal epithelial cells and suggests that EP has the potential therapeutic effect to intestinal inflammation.
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Antiinflamatorios , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Sulfato de Dextran/efectos adversos , Eclipta/química , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Mediadores de Inflamación/metabolismo , Fitoterapia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Enfermedad Aguda , Animales , Células Cultivadas , Colitis/metabolismo , Ciclooxigenasa 2/metabolismo , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Femenino , Células HT29 , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Mucosa Intestinal/citología , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Arctii Fructus is traditionally used in oriental pharmacies as an anti-inflammatory medicine. Although several studies have shown its anti-inflammatory effects, there have been no reports on its use in obesity related studies. In this study, the anti-obesity effect of Arctii Fructus was investigated in high-fat diet (HFD)-induced obese mice, and the effect was confirmed in white and primary cultured brown adipocytes. Arctii Fructus inhibited weight gain and reduced the mass of white adipose tissue in HFD-induced obese mice. Serum levels of triglyceride and LDL-cholesterol were reduced, and HDL-cholesterol was increased in the Arctii Fructus treated group. In 3T3-L1 cells, a water extract (WAF) and 70% EtOH extract (EtAF) of Arctii Fructus significantly inhibited adipogenesis and suppressed the expression of proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha. In particular, EtAF activated the phosphorylation of AMP-activated protein kinase. On the other hand, uncoupling protein 1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha, known as brown adipocytes specific genes, were increased in primary cultured brown adipocytes by WAF and EtAF. This study shows that Arctii Fructus prevents the development of obesity through the inhibition of white adipocyte differentiation and activation of brown adipocyte differentiation which suggests that Arctii Fructus could be an effective therapeutic for treating or preventing obesity.
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Adipocitos/efectos de los fármacos , Fármacos Antiobesidad/farmacología , Arctium/química , Grasas de la Dieta/efectos adversos , Extractos Vegetales/farmacología , Células 3T3-L1 , Animales , Fármacos Antiobesidad/química , Proteínas Potenciadoras de Unión a CCAAT/genética , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Supervivencia Celular/efectos de los fármacos , Grasas de la Dieta/administración & dosificación , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , PPAR gamma/genética , PPAR gamma/metabolismo , Extractos Vegetales/química , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Dojuksan is a traditional herbal medicine used in Korea and China to treat urinary diseases. In the present study, we aimed to examine the anti-inflammatory effects of an ethanol solvent extract of Dojuksan and a fraction (by bioassay-guided fractionation) derived from this extract, and to elucidate the specific mechanisms involved. The Dojuksan 30% ethanol extract (DEE) had a more significant and potent anti-inflammatory effect than the Dojuksan water extract (DWE). DEE markedly inhibited the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), as well as nuclear factor-κB (NF-κB) binding activity. We found that the anti-inflammatory effects of DEE were mediated by the induction of nuclear factor E2-related factor 2 (Nrf2)-dependent heme oxygenase-1 (HO-1). To further explore the anti-inflammatory effects of DEE, we generated 6 different fractions of DEE. Of these, DEE-5 decreased the production of NO more significantly than the other fractions. DEE-5 also significantly decreased the expression of iNOS and COX-2, and the production of NO, PGE2, TNF-α and IL-1ß. In addition, DEE-5 also significantly increased HO-1 levels; HO-1 significanlty contributed to the inhibitory effects of DEE-5 on the production of pro-inflammatory mediators. In this study, we determined whether the choice of extraction solvent affects the biological activity of Dojuksan, a traditional herbal formula. Our findings demonstrate that DEE and a fraction derived from this extract exerts anti-inflammatory effects through Nrf2dependent HO-1 expression, and that DEE may thus have greater potential therapeutic application than DWE.
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Medicamentos Herbarios Chinos/administración & dosificación , Hemo-Oxigenasa 1/biosíntesis , Inflamación/tratamiento farmacológico , Factor Nuclear 1 de Respiración/biosíntesis , Animales , Línea Celular , Ciclooxigenasa 2/biosíntesis , Dinoprostona/biosíntesis , Medicamentos Herbarios Chinos/química , Regulación de la Expresión Génica/efectos de los fármacos , Hemo-Oxigenasa 1/genética , Humanos , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/patología , Interleucina-1beta/biosíntesis , Lipopolisacáridos/toxicidad , Ratones , FN-kappa B/biosíntesis , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Factor Nuclear 1 de Respiración/genéticaRESUMEN
Lupeol is a triterpenoid commonly found in fruits and vegetables and is known to exhibit a wide range of biological activities, including antiinflammatory and anti-cancer effects. However, the effects of lupeol on acute pancreatitis specifically have not been well characterized. Here, we investigated the effects of lupeol on cerulein-induced acute pancreatitis in mice. Acute pancreatitis was induced via an intraperitoneal injection of cerulein (50 µg/kg). In the lupeol treatment group, lupeol was administered intraperitoneally (10, 25, or 50 mg/kg) 1 h before the first cerulein injection. Blood samples were taken to determine serum cytokine and amylase levels. The pancreas was rapidly removed for morphological examination and used in the myeloperoxidase assay, trypsin activity assay, and real-time reverse transcription polymerase chain reaction. In addition, we isolated pancreatic acinar cells using a collagenase method to examine the acinar cell viability. Lupeol administration significantly attenuated the severity of pancreatitis, as was shown by reduced pancreatic edema, and neutrophil infiltration. In addition, lupeol inhibited elevation of digestive enzymes and cytokine levels, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and interleukin (IL)-6. Furthermore, lupeol inhibited the cerulein-induced acinar cell death. In conclusion, these results suggest that lupeol exhibits protective effects on cerulein-induced acute pancreatitis.
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Antiinflamatorios/farmacología , Ceruletida , Pancreatitis/tratamiento farmacológico , Triterpenos Pentacíclicos/farmacología , Extractos Vegetales , Enfermedad Aguda , Amilasas , Animales , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Inyecciones Intraperitoneales , Lipasa/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Infiltración Neutrófila/efectos de los fármacos , Páncreas/efectos de los fármacos , Pancreatitis/inducido químicamente , Peroxidasa/metabolismo , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
In this study, we found that alpha-pinene (α-pinene) exhibits anti-inflammatory activity through the suppression of mitogen-activated protein kinases (MAPKs) and the nuclear factor-kappa B (NF-κB) pathway in mouse peritoneal macrophages. α-Pinene is found in the oils of many coniferous trees and rosemary. We investigated the inhibitory effects of α-Pinene on inflammatory responses induced by lipopolysaccharide (LPS) using mouse peritoneal macrophages. α-Pinene significantly decreased the LPS-induced production of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO). α-Pinene also inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in LPS-stimulated macrophages. Additionally, the activations of MAPKs and NF-κB were attenuated by means of α-pinene treatment. These results indicate that α-pinene has an anti-inflammatory effect and that it is a potential candidate as a new drug to treat various inflammatory diseases.
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Antiinflamatorios , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/fisiología , Macrófagos Peritoneales/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Monoterpenos/farmacología , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Monoterpenos Bicíclicos , Células Cultivadas , Ciclooxigenasa 2/metabolismo , Depresión Química , Inflamación/tratamiento farmacológico , Inflamación/genética , Interleucina-6/metabolismo , Lipopolisacáridos/efectos adversos , Lipopolisacáridos/antagonistas & inhibidores , Masculino , Ratones Endogámicos C57BL , Terapia Molecular Dirigida , Monoterpenos/uso terapéutico , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVES: We aimed to evaluate the anti-inflammatory and inhibitory effects of Lithospermum erythrorhizon (LE) on cerulein-induced acute pancreatitis (AP) in a mouse model. METHODS: Acute pancreatitis was induced via intraperitoneal injection of cerulein (50 µg/kg) every hour for 6 times. In the LE, water extract (100, 250, or 500 mg/kg) was administered intraperitoneally 1 hour before the first injection of cerulein. Six hours after AP, blood, the pancreas, and the lung were harvested for further examination. In addition, pancreatic acinar cells were isolated using a collagenase method, and then, we investigated the acinar cell viability and cytokine productions. RESULTS: Treatment with LE reduced pancreatic damage and AP-associated lung injury and attenuated the severity of AP, as evidenced by the reduction in neutrophil infiltration, serum amylase and lipase levels, trypsin activity, and proinflammatory cytokine expression. In addition, treatment with LE inhibited high mobility group box 1 expression in the pancreas during AP. In accordance with in vivo data, LE inhibited the cerulein-induced acinar cell death, cytokine productions, and high-mobility group box 1 expression. Furthermore, LE also inhibited the activation of p38 mitogen-activated protein kinases. CONCLUSIONS: These results suggest that LE plays a protective role during the development of AP by inhibiting the activation of p38.
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Antiinflamatorios/farmacología , Ceruletida , Lithospermum/química , Páncreas/efectos de los fármacos , Pancreatitis/prevención & control , Extractos Vegetales/farmacología , Enfermedad Aguda , Animales , Antiinflamatorios/aislamiento & purificación , Biomarcadores/sangre , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Citocinas/sangre , Citoprotección , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Activación Enzimática , Femenino , Proteína HMGB1/metabolismo , Mediadores de Inflamación/sangre , Ratones Endogámicos C57BL , Infiltración Neutrófila/efectos de los fármacos , Páncreas/metabolismo , Páncreas/patología , Pancreatitis/sangre , Pancreatitis/inducido químicamente , Pancreatitis/patología , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Índice de Severidad de la Enfermedad , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
It has been previously shown that Nardostachys jatamansi (NJ) exhibits anti-inflammatory properties against lipopolysaccharide (LPS) challenges. However, the potency of NJ constituents against LPS-induced inflammatory responses has not been examined. In this present study, we determined which NJ extract fractions exhibit inhibitory effects against LPS-induced inflammatory responses. Among the NJ fractions, NJ-1, NJ-3, NJ-4, and NJ-6 inhibited LPS-induced production of NO. The NJ-3, NJ-4, and NJ-6 fractions also inhibited the production of cytokines, such as IL-1 ß , IL-6, and TNF- α . However, NJ-1, NJ-3, NJ-4, and NJ-6 showed differential inhibitory mechanisms against LPS-induced inflammatory responses. NJ-1, NJ-3, and NJ-4 inhibited LPS-induced activation of c-jun NH2-terminal kinase (JNK) and p38 but did not affect activation of extracellular signal-regulated kinase (ERK) or NF- κ B. On the other hand, NJ-6 inhibited activation of MAPKs and NF- κ B. In addition, in vivo experiments revealed that administration of NJ-1, NJ-3, NJ-4, and NJ-6 reduced LPS-induced endotoxin shock, with NJ-6 especially showing a marked protective effect. Taken together, these results provide the evidence for the potential of selective NJ fractions against LPS-induced inflammation. Thus, it will be advantageous to further isolate and determine single effective compounds from these potent fractions.
RESUMEN
OBJECTIVE: The aim of this study was to evaluate the effects of Opuntia humifusa (OH) on cerulein-induced acute pancreatitis (AP). METHODS: Acute pancreatitis was induced via intraperitoneal injection of cholecystokinin analog cerulein (50 µg/kg). In the OH pretreatment group, OH was administered intraperitoneally (100, 250, or 500 mg/kg) 1 hour before first cerulein injection. In the posttreatment group, OH was administered intraperitoneally (500 mg/kg) 1 hour after the first cerulein injection. Furthermore, we isolated the pancreatic acinar cells using collagenase method, then investigated the acinar cell viability, cytokine productions, and the regulating mechanisms. RESULTS: The both pretreatment and posttreatment of OH treatment attenuated the severity of AP, as shown by the histology of the pancreas and lung, and inhibited neutrophil infiltration; serum amylase and lipase activities; proinflammatory cytokine expression such as interleukin 1, interleukin 6, and tumor necrosis factor α; and cell death including apoptosis and necrosis. Furthermore, OH inhibited the activation of c-Jun N-terminal kinases. CONCLUSIONS: These results suggest that OH reduces the severity of AP by inhibiting acinar cell death through c-Jun N-terminal kinases.
Asunto(s)
Opuntia/química , Páncreas/efectos de los fármacos , Pancreatitis/prevención & control , Extractos Vegetales/farmacología , Células Acinares/efectos de los fármacos , Células Acinares/metabolismo , Enfermedad Aguda , Amilasas/sangre , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ceruletida , Citocinas/genética , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Expresión Génica/efectos de los fármacos , Proteína HMGB1/metabolismo , Inyecciones Intraperitoneales , Lipasa/sangre , Ratones , Ratones Endogámicos C57BL , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Páncreas/metabolismo , Páncreas/patología , Pancreatitis/sangre , Pancreatitis/inducido químicamente , Extractos Vegetales/administración & dosificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de TiempoRESUMEN
Ixeris dentata (ID) is an herbal medicine used in Asian countries to treat indigestion, pneumonia, hepatitis, contusions, and tumors; however, its effect on intestinal inflammation is unknown. Thus, we investigated the effect of ID in the dextran sulfate sodium (DSS) model of colitis in female BALB/c mice; animals were evaluated after seven days of DSS treatment. DSS-treated mice showed considerable clinical signs, including weight loss, reduced colon length, colonic epithelial injury, infiltration of inflammatory cells in the colon tissue, and upregulation of inflammatory mediators. However, administration of ID attenuated body weight loss, colon shortening, and the increase in disease activity index score. ID also significantly decreased the colonic mucosal injury and the number of infiltrating mast cells. Moreover, ID inhibited the expressions of cyclooxygenase-2 and hypoxia-inducible factor-1 α in colon tissue. Taken together, the results provide experimental evidence that ID might be a useful therapy for patients with ulcerative colitis.
Asunto(s)
Dieta , Nardostachys/química , Páncreas/efectos de los fármacos , Pancreatitis/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Deficiencia de Colina/complicaciones , Modelos Animales de Enfermedad , Femenino , Metionina/deficiencia , Ratones , Ratones Endogámicos C57BL , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/prevención & control , Páncreas/patología , Pancreatitis/etiología , Pancreatitis/patología , Plantas Medicinales , Factores de TiempoRESUMEN
Previously, we reported that Nardostachys jatamansi (NJ) attenuated cerulein-induced mild acute pancreatitis (AP). In the present study, we investigated the ability of NJ to ameliorate severe acute pancreatitis (SAP) induced by a choline-deficient diet supplemented with ethionine (CDE). An NJ extract was orally administered ad libitum via the water during administration of the CDE. After three days, the CDE was replaced with a normal diet. After four days of normal feeding the mice were sacrificed and the blood and pancreas were obtained for further investigation. NJ treatment reduced SAP-induced pancreatic damage, as shown by histology. NJ treatment also inhibited neutrophil infiltration into the pancreas. NJ also inhibited the secretion of digestive enzymes and cytokine production, and inhibited the activation of mitogen-activated protein kinases (MAPKs) in the SAP-challenged pancreas. These data suggest that NJ protects against pancreatic injury in CDE-induced SAP by deactivating MAPKs.
RESUMEN
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.
Asunto(s)
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
Nardostachys jatamansi (NJ) belonging to the Valerianaceae family has been used as a remedy for gastrointestinal inflammatory diseases for decades. However, the potential for NJ to ameliorate alcoholic chronic pancreatitis (ACP) is unknown. The aim of this study was to examine the inhibitory effects of NJ on ACP. C57black/6 mice received ethanol injections intraperitoneally for 3 weeks against a background of cerulein-induced acute pancreatitis. During ACP, NJ was ad libitum administrated orally with water. After 3 weeks of treatment, the pancreas was harvested for histological examination. NJ treatment increased the pancreatic acinar cell survival (confirmed by amylase level testing) and reduced collagen deposition and pancreatic stellate cell (PSC) activation. In addition, NJ treatment reduced the activation but not death of PSC. In conclusion, our results suggest that NJ attenuated ACP through the inhibition of PSC activation.