RESUMEN
Chronic inflammation is an underlying risk factor of colon cancer, and NF-κB plays a critical role in the development of inflammation-associated colon cancer in an AOM/DSS mouse model. The aim of this study was to determine whether the standardized ethanol extract obtained from the aerial parts of Artemisia princeps Pampanini cv. Sajabal (EAPP) is effective at preventing inflammation-associated colon cancer, and if so, to identify the signaling pathways involved. In the present study, protective efficacy of EAPP on tumor formation and the infiltrations of monocytes and macrophages in colons of an AOM/DSS mouse model were evaluated. It was found that colitis and tumor burdens showed statistically meaningful improvements after EAPP administration. Furthermore, these improvements were accompanied by a reduction in NF-κB activity and in the levels of NF-κB-dependent pro-survival proteins, that is, survivin, cFLIP, XIAP, and Bcl-2. In vitro, EAPP significantly reduced NF-κB activation and the levels of IL-1ß and IL-8 mRNA and pro-survival proteins in HT-29 and HCT-116 colon cancer cells. Furthermore, EAPP caused caspase-dependent apoptosis. Based on these results, the authors suggest EAPP suppresses inflammatory responses and induces apoptosis partly via NF-κB inactivation, and that EAPP could be useful for the prevention of colitis-associated tumorigenesis.
Asunto(s)
Anticarcinógenos/farmacología , Artemisia/química , Colitis/complicaciones , Neoplasias del Colon/prevención & control , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Animales , Apoptosis/efectos de los fármacos , Carcinogénesis/efectos de los fármacos , Neoplasias del Colon/etiología , Células HCT116 , Células HT29 , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Macrófagos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos ICR , Monocitos/efectos de los fármacos , FN-kappa B/antagonistas & inhibidores , Componentes Aéreos de las Plantas/química , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Amomum tsao-ko Crevost et Lemarié (Zingiberaceae) has traditionally been used to treat inflammatory and infectious diseases, such as throat infections, malaria, abdominal pain and diarrhoea. This study was designed to assess the anti-inflammatory effects and the molecular mechanisms of the methanol extract of A. tsao-ko (AOM) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and in a murine model of sepsis. In LPS-induced RAW 264.7 macrophages, AOM reduced the production of nitric oxide (NO) by inhibiting inducible nitric oxide synthase (iNOS) expression, and increased heme oxygenase-1 (HO-1) expression at the protein and mRNA levels. Pretreatment with SnPP (a selective inhibitor of HO-1) and silencing HO-1 using siRNA prevented the AOM-mediated inhibition of NO production and iNOS expression. Furthermore, AOM increased the expression and nuclear accumulation of NF-E2-related factor 2 (Nrf2), which enhanced Nrf2 binding to antioxidant response element (ARE). In addition, AOM induced the phosphorylation of extracellular regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) and generated reactive oxygen species (ROS). Furthermore, pretreatment with N-acetyl-l-cysteine (NAC; a ROS scavenger) diminished the AOM-induced phosphorylation of ERK and JNK and AOM-induced HO-1 expression, suggesting that ERK and JNK are downstream mediators of ROS during the AOM-induced signalling of HO-1 expression. In LPS-induced endotoxaemic mice, pretreatment with AOM reduced NO serum levels and liver iNOS expression and increased HO-1 expression and survival rates. These results indicate that AOM strongly inhibits LPS-induced NO production by activating the ROS/MAPKs/Nrf2-mediated HO-1 signalling pathway, and supports its pharmacological effects on inflammatory diseases.
Asunto(s)
Amomum , Antiinflamatorios/farmacología , Hemo-Oxigenasa 1/biosíntesis , Lipopolisacáridos , Macrófagos/efectos de los fármacos , Proteínas de la Membrana/biosíntesis , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Extractos Vegetales/farmacología , Sepsis/tratamiento farmacológico , Amomum/química , Animales , Antiinflamatorios/aislamiento & purificación , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Inducción Enzimática , Inhibidores Enzimáticos/farmacología , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Frutas , Hemo-Oxigenasa 1/antagonistas & inhibidores , Hemo-Oxigenasa 1/genética , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Macrófagos/enzimología , Masculino , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Células RAW 264.7 , Interferencia de ARN , ARN Mensajero/biosíntesis , Especies Reactivas de Oxígeno/metabolismo , Sepsis/inducido químicamente , Sepsis/enzimología , Sepsis/genética , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , TransfecciónRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Rubus coreanus Miquel (Rosaceae), the Korean black raspberry, has traditionally been used to treat inflammatory diseases including diarrhea, asthma, stomach ailment, and cancer. Although previous studies showed that the 19α-hydroxyursane-type triterpenoids isolated from Rubus coreanus exerted anti-inflammatory activities, their effects on ulcerative colitis and mode of action have not been explored. This study was designed to assess the anti-inflammatory effects and the molecular mechanisms involving19α-hydroxyursane-type triterpenoid-rich fraction from Rubus coreanus (TFRC) on a mice model of colitis and lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. MATERIALS AND METHODS: Experimental colitis was induced by DSS for 7 days in ICR mice. Disease activity indices (DAI) took into account body weight, stool consistency, and gross bleeding. Histological changes and macrophage accumulation were observed by immunohistochemical analysis. Pro-inflammatory markers were determined using immunoassays, RT-PCR, and real time PCR. Signaling pathway involving nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) activation was determined by luciferase assay and Western blotting. RESULTS: In DSS-induced colitis mice, TFRC improved DAIs and pathological characteristics including colon shortening and colonic epithelium injury. TFRC suppressed tissue levels of pro-inflammatory cytokines and reduced macrophage infiltration into colonic tissues. In LPS-induced RAW 264.7 macrophages, TFRC inhibited the production of NO, PGE2, and pro-inflammatory cytokines by down-regulating the activation of NF-κB and p38 MAPK signaling. CONCLUSION: The study demonstrates that TFRC has potent anti-inflammatory effects on DSS-induced colonic injury and LPS-induced macrophage activation, and supports its possible therapeutic and preventive roles in colitis.
Asunto(s)
Colitis/prevención & control , Sulfato de Dextran/toxicidad , Lipopolisacáridos/toxicidad , Macrófagos/efectos de los fármacos , Extractos Vegetales/farmacología , Rubus/química , Triterpenos/análisis , Animales , Secuencia de Bases , Línea Celular , Colitis/inducido químicamente , Citocinas/biosíntesis , Citocinas/genética , Cartilla de ADN , Mediadores de Inflamación/metabolismo , Macrófagos/metabolismo , Ratones , Extractos Vegetales/química , Reacción en Cadena de la PolimerasaRESUMEN
Much is known about the bioactive properties of lignans from the fruits of Schisandra chinensis. However, very little work has been done to determine the properties of sesquiterpenes in the fruits of S. chinensis. The aim of the present study was to investigate the anti-inflammatory potential of new sesquiterpenes (ß-chamigrenal, ß-chamigrenic acid, α-ylangenol, and α-ylangenyl acetate) isolated from the fruits of S. chinensis and to explore their effect on macrophages stimulated with lipopolysaccharide. Of these four sesquiterpenes, ß-chamigrenal most significantly suppressed lipopolysaccharide-induced nitric oxide and prostaglandin E2 production in RAW 264.7 macrophages (47.21 ± 4.54â% and 51.61 ± 3.95â% at 50 µM, respectively). Molecularly, the inhibitory activity of ß-chamigrenal on nitric oxide production was mediated by suppressing inducible nitric oxide synthase activity but not its expression. In the prostaglandin E2 synthesis pathway, ß-chamigrenal prevented the upregulation of inducible microsomal prostaglandin E synthase-1 expression after stimulation with lipopolysaccharide. Conversely, ß-chamigrenal had no effect on the expression and enzyme activity of cyclooxygenase-2. In addition, the expression of early growth response factor-1, a key transcription factor of microsomal prostaglandin E synthase-1 expression, was inhibited by ß-chamigrenal. These results may suggest a possible anti-inflammatory activity of ß-chamigrenal which has to be proven in in vivo experiments.
Asunto(s)
Antiinflamatorios/farmacología , Dinoprostona/metabolismo , Óxido Nítrico/metabolismo , Extractos Vegetales/farmacología , Schisandra/química , Sesquiterpenos/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Línea Celular Tumoral , Frutas/química , Regulación de la Expresión Génica/efectos de los fármacos , Lipopolisacáridos/efectos adversos , Macrófagos/efectos de los fármacos , Ratones , Óxido Nítrico Sintasa de Tipo II/metabolismo , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Regulación hacia ArribaRESUMEN
This study was undertaken to investigate the anti-arthritic potential of a standardized ethyl acetate fraction from the roots of Brassica rapa (EABR) and to explore the molecular mechanisms in adjuvant-induced arthritic rats and macrophages. In AIA-induced arthritic rats, EABR significantly reduced paw swelling, an arthritic index, serum rheumatoid factor, and tissue expression ratio of RANKL/OPG versus vehicle-administered group. This was found to be well correlated with significant suppressions in productions of PGE2, NO, and pro-inflammatory cytokines and in activations of NF-κB in AIA-induced paw tissues and LPS-induced macrophages. EABR attenuated NF-κB activation by reducing the nuclear translocation and phosphorylation of the p65 NF-κB, which were accompanied by parallel reductions in the degradation and phosphorylation of IκBα after blocking the phosphorylation mediated IKK activation. The findings suggest EABR exerts its anti-arthritic and anti-inflammatory properties via NF-κB inactivation in vitro and in vivo, and that EABR is a potential therapeutic for the treatment of arthritis and inflammation-associated disorders.
Asunto(s)
Acetatos/química , Artritis Experimental/prevención & control , Brassica rapa/química , Inflamación/prevención & control , FN-kappa B/antagonistas & inhibidores , Extractos Vegetales/farmacología , Animales , Artritis Experimental/metabolismo , Secuencia de Bases , Línea Celular , Cromatografía Líquida de Alta Presión , Cartilla de ADN , Inflamación/genética , Inflamación/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , FN-kappa B/metabolismo , Raíces de Plantas/química , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
In this study, the authors investigated the molecular mechanism underlying the antiinflammatory effects of the chloroform fraction of the peel of 'Jayoung' (CFPJ), a color-fleshed potato, on lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and in mice with dextran sulfate sodium (DSS)-induced colitis. CFPJ inhibited the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the transcription level, and attenuated the transcriptional activity of nuclear factor-κB (NF-κB) by reducing the translocation of NF-κB depending on degradation of inhibitory κB-α (IκB-α). Furthermore, CFPJ attenuated the phosphorylations of mitogen-activated protein kinase kinases3/6 (MKK3/6) and of p38. In colitis model, CFPJ significantly reduced the severity of colitis and the productions and protein levels of pro-inflammatory mediators in colonic tissue. These results suggest that the anti-inflammatory effects of CFPJ are associated with the suppression of NF-κB and p38 activation in macrophages, and support its possible therapeutic role for the treatment of colitis.
Asunto(s)
Cloroformo/química , Colitis/prevención & control , Sulfato de Dextran/toxicidad , Epidermis/efectos de los fármacos , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Extractos Vegetales/farmacología , Solanum tuberosum/química , Animales , Línea Celular , Colitis/inducido químicamente , Colitis/metabolismo , Ciclooxigenasa 2/metabolismo , Mediadores de Inflamación/metabolismo , MAP Quinasa Quinasa 3/metabolismo , MAP Quinasa Quinasa 6/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
In this study, we aimed to identify the compounds in Eclipta prostrata responsible for its anti-inflammatory effects using an in vitro bioassay. Three triterpenoids, eclalbasaponin I, eclalbasaponin II, and echinocystic acid, were isolated from an EtOAc fraction of the 70 % EtOH extract of E. prostrata by activity-guided fractionation based on the inhibition of nitric oxide release from lipopolysaccharide-induced RAW 264.7 macrophages. Of these three triterpenoids, echinocystic acid inhibited lipopolysaccharide-induced production of nitric oxide and cytokines such as tumor necrosis factor-α and interleukin-6. Consistent with these observations, echinocystic acid concentration-dependently inhibited lipopolysaccharide-induced inducible nitric oxide synthase expression at the protein level and inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-6 expression at the mRNA level, and inhibited lipopolysaccharide-induced iNOS promoter binding activity. In addition, echinocystic acid suppressed the lipopolysaccharide-induced transcriptional activity of nuclear factor-κB by blocking the nuclear translocation of p65.
Asunto(s)
Antiinflamatorios/farmacología , Eclipta/química , FN-kappa B/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Triterpenos/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Línea Celular , Regulación hacia Abajo/efectos de los fármacos , Regulación de la Expresión Génica , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , Ácido Oleanólico/aislamiento & purificación , Ácido Oleanólico/farmacología , Plantas Medicinales , Saponinas/química , Saponinas/aislamiento & purificación , Saponinas/farmacología , Triterpenos/química , Triterpenos/aislamiento & purificación , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
In mammals, the increased secretion of arginine-vasopressin (AVP) (antidiuretic hormone) and oxytocin (natriuretic hormone) is a key physiological response to hyperosmotic stress. In this study, we examined whether chronic hyperosmotic stress weakens GABA(A) receptor-mediated synaptic inhibition in rat hypothalamic magnocellular neurosecretory cells (MNCs) secreting these hormones. Gramicidin-perforated recordings of MNCs in acute hypothalamic slices prepared from control rats and ones subjected to the chronic hyperosmotic stress revealed that this challenge not only attenuated the GABAergic inhibition but actually converted it into excitation. The hyperosmotic stress caused a profound depolarizing shift in the reversal potential of GABAergic response (E(GABA)) in MNCs. This E(GABA) shift was associated with increased expression of Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) in MNCs and was blocked by the NKCC inhibitor bumetanide as well as by decreasing NKCC activity through a reduction of extracellular sodium. Blocking central oxytocin receptors during the hyperosmotic stress prevented the switch to GABAergic excitation. Finally, intravenous injection of the GABA(A) receptor antagonist bicuculline lowered the plasma levels of AVP and oxytocin in rats under the chronic hyperosmotic stress. We conclude that the GABAergic responses of MNCs switch between inhibition and excitation in response to physiological needs through the regulation of transmembrane Cl(-) gradients.
Asunto(s)
Inhibición Neural/fisiología , Neuronas/fisiología , Presión Osmótica/fisiología , Estrés Fisiológico/fisiología , Vasopresinas/fisiología , Ácido gamma-Aminobutírico/fisiología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Bicuculina/farmacología , Bumetanida/farmacología , Estimulación Eléctrica/métodos , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Hipotálamo/fisiología , Masculino , Oxitocina/sangre , Oxitocina/fisiología , Técnicas de Placa-Clamp , Ratas , Ratas Sprague-Dawley , Sodio/metabolismo , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/farmacología , Simportadores de Cloruro de Sodio-Potasio/biosíntesis , Miembro 2 de la Familia de Transportadores de Soluto 12 , Estrés Fisiológico/efectos de los fármacos , Vasopresinas/sangreRESUMEN
Alzheimer's disease (AD) is a neurodegenerative disorder associated with progressive cognitive and memory loss and neuronal cell death. Current therapeutic strategies for AD are very limited; thus, traditional herbal medicines or their active constituents receive much attention. The aim of this study was to investigate the cognitive enhancing effects of salvianolic acid B (SalB) isolated from Salvia miltiorrhiza and its ameliorating effects on various drug-induced amnesic models using the passive avoidance, Y-maze, and Morris water maze tasks. Drug-induced amnesia was induced by administering scopolamine, diazepam, muscimol, or amyloid-ß (Aß)(25-35) peptide. SalB (10 mg/kg, p.o.) was found to significantly reverse the cognitive impairments induced by scopolamine (1 mg/kg, i.p.) or Aß(25-35) (10 nmol/5 µl, i.c.v.) injection. This ameliorating effect of SalB was antagonized by the GABA(A) receptor agonists, muscimol or diazepam, respectively. In addition, SalB alone was capable of improving cognitive performances. Furthermore, SalB (100 µM) was found to inhibit GABA-induced outward Cl(-) currents in single hippocampal CA1 neuron. These results suggest that the observed ameliorations of cholinergic dysfunction- or Aß(25-35)-induced memory impairment by SalB were mediated, in part, via the GABAergic neurotransmitter system after a single administration.
Asunto(s)
Péptidos beta-Amiloides/efectos adversos , Benzofuranos/uso terapéutico , Antagonistas Colinérgicos/efectos adversos , Trastornos del Conocimiento/inducido químicamente , Trastornos del Conocimiento/tratamiento farmacológico , Fragmentos de Péptidos/efectos adversos , Animales , Animales Recién Nacidos , Benzofuranos/química , Inhibidores de la Colinesterasa/efectos adversos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Hipocampo/citología , Técnicas In Vitro , Inyecciones Intraventriculares , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Potenciales de la Membrana/efectos de los fármacos , Ratones , Neuronas/efectos de los fármacos , Técnicas de Placa-Clamp , Embarazo , Ratas , Tacrina/efectos adversos , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
In an attempt to identify bioactive natural products with anti-inflammatory activity, we evaluated the anti-inflammatory potential of the indole-containing fraction from the roots of Brassica rapa (IBR) (Family Brassicaceae) and the underlying mechanisms. Initially, we examined the inhibitory effect of IBR on the production of pro-inflammatory mediators in vitro and then evaluated its in vivo anti-inflammatory effects. IBR was found to concentration-dependently reduce the productions of nitric oxide, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced macrophages. Consistent with these findings, IBR suppressed the LPS-induced expressions of inducible nitric oxide synthase (iNOS) at the protein level and of iNOS, TNF-α, and IL-6 at the mRNA level. Furthermore, IBR attenuated LPS-induced DNA-binding activities of nuclear factor-κB (NF-κB), and this was accompanied by a parallel reduction in the degradation and phosphorylation of inhibitory κBα and, consequently, by a reduction in the nuclear translocation of the p65 subunit of NF-κB. In addition, treatment with IBR inhibited carrageenan-induced paw edema in rats and acetic acid-induced writing response in mice. Taken together, our data suggest that the expressional inhibitions of iNOS, TNF-α, and IL-6 caused by an attenuation of NF-κB activation are responsible for the anti-inflammatory and antinociceptive activity of IBR.
Asunto(s)
Brassica rapa/química , Indoles/farmacología , FN-kappa B/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/farmacología , Línea Celular , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Dinoprostona/antagonistas & inhibidores , Dinoprostona/sangre , Regulación de la Expresión Génica , Humanos , Interleucina-6/antagonistas & inhibidores , Interleucina-6/sangre , Lipopolisacáridos/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , FN-kappa B/genética , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fosforilación/efectos de los fármacos , Raíces de Plantas/química , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/sangreRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Patrinia scabiosaefolia Fisch is used in folk medicines to treat intestinal abscesses, acute appendicitis, and dysentery in Asia. Although recent reports indicate that Patrinia scabiosaefolia has sedative and anti-tumor effects, its effects on ulcerative colitis have not been previously explored. AIM OF THE STUDY: To determine the effects and the mode of action of the methanol extract of the roots of Patrinia scabiosaefolia (PME) on a model of colitis in mice induced by dextran sulfate sodium (DSS). MATERIALS AND METHODS: We induced colitis using DSS in 5-week-ICR mice over 7 days and estimated disease activity index (DAI), which took into account body weight, stool consistency, gross bleeding, and tissue myeloperoxidase (MPO) accumulation. Colon lengths and spleen weights were measured. Histological changes were observed by H&E staining. Pro-inflammatory mediators, namely, nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), were determined using Griess assays, immunoassays, and by quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR), respectively. RESULTS: PME significantly attenuated DSS-induced DAI scores and tissue MPO accumulation, which implied that it suppressed weight loss, diarrhea, gross bleeding, and the infiltrations of immune cells. PME administration also effectively and dose-dependently prevented shortening of colon length and enlargement of spleen size. Histological examinations indicated that PME suppressed edema, mucosal damage, and the loss of crypts induced by DSS. Furthermore, PME inhibited the abnormal secretions and mRNA expressions of pro-inflammatory cytokines, such as, TNF-α, IL-1ß, and IL-6. CONCLUSION: These results suggest that PME has an anti-inflammatory effect at colorectal sites that is due to the down-regulations of the productions and expressions of inflammatory mediators, and that it may have therapeutic value in the setting of inflammatory bowel disease (IBD).
Asunto(s)
Antiinflamatorios/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Colon/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Patrinia , Fitoterapia , Extractos Vegetales/uso terapéutico , Animales , Antiinflamatorios/farmacología , Quimiotaxis de Leucocito/efectos de los fármacos , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/patología , Colon/metabolismo , Colon/patología , Citocinas/genética , Citocinas/metabolismo , Sulfato de Dextran , Diarrea/prevención & control , Relación Dosis-Respuesta a Droga , Edema/prevención & control , Hemorragia/prevención & control , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , Ratones , Ratones Endogámicos ICR , Tamaño de los Órganos/efectos de los fármacos , Peroxidasa/metabolismo , Extractos Vegetales/farmacología , Raíces de Plantas , ARN Mensajero/metabolismo , Bazo/efectos de los fármacos , Pérdida de PesoRESUMEN
Anemarrhena asphodeloides is widely used in traditional Chinese medicine, and is known to have anti-diabetic and diuretic effects. In this study, we evaluated the anti-inflammatory effects of anemarsaponin B (ASB), a steroidal saponin isolated from the rhizomes of A. asphodeloides (Liliaceae), in LPS-stimulated RAW 264.7 macrophage cell line. ASB significantly and dose-dependently decreased the protein and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). ASB also reduced the expressions and productions of pro-inflammatory cytokines, including those of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Electrophoretic mobility shift assay (EMSA) and reporter gene assays revealed that ASB attenuated the LPS-induced DNA binding and transcriptional activity of nuclear factor-kappa B (NF-kappaB). In addition, it was found that pretreatment with ASB significantly inhibited the nuclear translocation of the p65 subunit of NF-kappaB by blocking the phosphorylation of inhibitory kappa B-alpha (IkappaB-alpha). On the other hand, ASB inhibited the phosphorylation of MAP kinase kinases 3/6 (MKK3/6) and mixed lineage kinase 3 (MLK3), which are both involved in the p38 pathway. Taken together, these results suggest that anti-inflammatory effect of ASB in LPS-treated RAW 264.7 macrophages is associated with the inhibition of NF-kappaB transcriptional activity, possibly via the p38 MAP kinase pathway.
Asunto(s)
Anemarrhena/química , Antiinflamatorios no Esteroideos , Macrófagos/efectos de los fármacos , FN-kappa B/biosíntesis , Saponinas/farmacología , Triterpenos/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/biosíntesis , Western Blotting , Línea Celular , Ciclooxigenasa 2/metabolismo , Dinoprostona/metabolismo , Ensayo de Cambio de Movilidad Electroforética , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Raíces de Plantas/química , ARN/biosíntesis , ARN/aislamiento & purificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Sales de Tetrazolio , Tiazoles , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
In the present study, the antiproliferative effects of the ethanol extract of Artemisia princeps Pampanini (EAPP) and the mechanism involved were investigated. Of the various cancer cells examined, human neuroblastoma A172 cells were most sensitive to EAPP, and their proliferation was dose- and time-dependently inhibited by EAPP. DNA flow cytometry analysis indicated that EAPP notably induced the G(1) phase arrest in A172 cells. Of the G(1) phase cycle-related proteins examined, the expressions of cyclin-dependent kinase (CDK) 2, CDK4, and CDK6 and of cyclin D(1), D(2), and D(3) were found to be markedly reduced by EAPP, whereas cyclin E was unaffected. Moreover, the protein and mRNA levels of the CDK inhibitors p16(INK4a), p21(CIP1/WAF1), and p27(KIP1) were increased, and the activities of CDK2, CDK4, and CDK6 were reduced. Furthermore, the expressions of E2F-1 and of phosphorylated pRb were also decreased, and the protein levels of p53 and pp53 (Ser15) were increased. Up-regulation of p21(CIP1/WAF1) was found to be mediated by a p53-dependent pathway in EAPP-induced G(1)-arrested A172 cells. When these data are taken together, the EAPP was found to potently inhibit the proliferation of human neuroblastoma A172 cells via G(1) phase cell cycle arrest.
Asunto(s)
Artemisia/química , Fase G1/efectos de los fármacos , Neuroblastoma/patología , Extractos Vegetales/farmacología , Proteína p53 Supresora de Tumor/fisiología , División Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Quinasas Ciclina-Dependientes/genética , Quinasas Ciclina-Dependientes/fisiología , ADN/análisis , Etanol , Expresión Génica , HumanosRESUMEN
Oroxylin A is a flavonoid and was originally isolated from the root of Scutellaria baicalensis Georgi., one of the most important medicinal herbs in traditional Chinese medicine. The aim of this study was to investigate the ameliorating effects of oroxylin A on memory impairment using the passive avoidance test, the Y-maze test, and the Morris water maze test in mice. Drug-induced amnesia was induced by administering scopolamine (1 mg/kg, i.p.) or diazepam (1 mg/kg, i.p.). Oroxylin A (5 mg/kg) significantly reversed cognitive impairments in mice by passive avoidance and the Y-maze testing (P<.05). Oroxylin A also improved escape latencies in training trials and increased swimming times and distances within the target zone of the Morris water maze (P<.05). Moreover, the ameliorating effects of oroxylin A were antagonized by both muscimol and diazepam (0.25 mg/kg, i.p., respectively), which are GABA(A) receptor agonists. Furthermore, oroxylin A (100 microM) was found to inhibit GABA-induced inward Cl(-) current in a single cortical neuron. These results suggest that oroxylin A may be useful for the treatment of cognitive impairments induced by cholinergic dysfunction via the GABAergic nervous system.
Asunto(s)
Reacción de Prevención/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Flavonoides/farmacología , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Receptores de GABA-A/efectos de los fármacos , Amnesia/inducido químicamente , Amnesia/prevención & control , Análisis de Varianza , Animales , Reacción de Prevención/fisiología , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/fisiopatología , Femenino , Masculino , Aprendizaje por Laberinto/fisiología , Memoria/fisiología , Ratones , Ratones Endogámicos ICR , Antagonistas Muscarínicos , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiología , Receptores de GABA-A/fisiología , Escopolamina , Estadísticas no ParamétricasRESUMEN
Moxibustion is one of the major healing techniques in Oriental medicine. It has been widely used in many diseases such as rheumatoid arthritis, Hashimoto disease, breech presentation, etc. However, till now, effects of moxibustion on natural killer (NK) cell activity and relations between sympathetic nerve system (SNS) and the immune alteration induced by moxibustion were not well studied. This study was designed to evaluate effects of moxibustion on NK cell activity and the intervention of SNS in the alteration of NK cell activity induced by moxibustion. Splenic NK cell cytotoxicity was measured in a standard 4-hour 51Cr release assay. We measured the NK cell cytotoxicity after moxibustion stimulation for 1, 3, 5 and 7 days, and also measured the NK cell cytotoxicity after 3 and 7 days burn stimulation with similar temperature. Interleukin (IL)-2, -4 and interferon (INF)-gamma in serum were measured by rat IL-2, -4 and INF-gamma ELISA test kit. To evaluate the effects of sympathectomy on alteration of NK cell cytotoxicity, 6-hydroxydopamine (6-OHDA: 50 mg/kg) was used. We showed that NK cell activity of moxibustion stimulation group increased at the 3rd day, and declined at the 7th day in comparison with that of the control group. In the moxibustion stimulation group, NK cell activity was significantly higher than the sham group at the 3rd day. On the contrary, in the burn stimulation group, NK cell activity was significantly higher than that of the sham groups at 3rd and 7th days. INF-gamma level after 3 days in the moxibustion stimulation group was significantly higher than that of the sham group. IL-2 level among groups were not different. IL-4 was not detected in serum with this method. Sympathectomy abolished the NK cell activity alteration induced by moxibustion. The results suggest that moxibustion modulates NK cell activity, along with INF-gamma, and SNS is mediating these effects.
Asunto(s)
Células Asesinas Naturales/fisiología , Moxibustión , Sistema Nervioso Simpático/fisiología , Animales , Ensayo de Inmunoadsorción Enzimática , Interferón gamma/análisis , Interferón gamma/farmacología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND/OBJECTIVE: Neuroendocrine hormones are derived from the hypothalamus. The central nervous system, particularly the hypothalamus, is capable of modulating the cytolytic activity of adherent natural killer (NK) cells. In addition, electroacupuncture (EA) stimulation of the Zusanli (ST36) acupoint enhances splenic NK cell and cytokine activities in rats. However, it is still unclear whether the anterior hypothalamus affects this immunomodulation. Therefore, the aim of the present study was to examine the effect of EA stimulation at the Zusanli acupoint on the NK cell activity modulated by an anterior hypothalamic area lesion. METHODS: Male Sprague-Dawley rats were used. Lesions were placed by means of a direct current through a concentric electrode. The electric acupuncture stimulation was delivered for 30 min per each experiment at the right ST36 acupoint with an electrical stimulator. The NK cell activity of the spleen was measured by a fluorescence assay. RESULTS: The NK cell activity was significantly reduced on the 2nd day after the lesion, but was restored to that of the sham group by the 7th day. However, when EA was applied for 2 days after the operation, the NK cell activity of the lesion group was restored to that of the sham group. After 7 days of EA, the NK cell activity of the lesion group was slightly higher than that of the sham group. CONCLUSION: From these results, we can suggest that EA enhances or restores the NK cell activity suppressed by an anterior hypothalamic area lesion.
Asunto(s)
Núcleo Hipotalámico Anterior/inmunología , Núcleo Hipotalámico Anterior/patología , Electroacupuntura , Tolerancia Inmunológica/inmunología , Células Asesinas Naturales/fisiología , Neuroinmunomodulación/fisiología , Animales , Desnervación , Masculino , Ratas , Ratas Sprague-Dawley , Bazo/citología , Bazo/inmunologíaRESUMEN
The effects of chemical sympathectomy on moxibustion-induced changes in splenic natural killer (NK) cell cytotoxicity, T and B cell proliferation were studied. Direct moxibustion was applied to the unilateral Zusanli region. NK cell cytotoxicity was suppressed by moxibustion in both vehicle-treated rats and sympathectomized rats. T cell proliferation was not affected by moxibustion. B cell proliferation showed no significant change in vehicle-treated rats, but an increase was seen in sympathectomized rats treated with moxibustion. Sympathectomy alone induced an augmentation of NK cell cytotoxicity and a suppression of T cell proliferation. These results suggest that the sympathetic nervous system (SNS) has no significant role in the mechanism of moxibustion-induced immunomodulation.