RESUMEN
Neuropathic pain is a refractory disease that occurs across the world and pharmacotherapy has limited efficacy and/or safety. This disease imposes a significant burden on both the somatic and mental health of patients; indeed, some patients have referred to neuropathic pain as being 'worse than death'. The pharmacological agents that are used to treat neuropathic pain at present can produce mild effects in certain patients, and induce many adverse reactions, such as sedation, dizziness, vomiting, and peripheral oedema. Therefore, there is an urgent need to discover novel drugs that are safer and more effective. Natural compounds from medical plants have become potential sources of analgesics, and evidence has shown that glycosides alleviated neuropathic pain via regulating oxidative stress, transcriptional regulation, ion channels, membrane receptors and so on. In this review, we summarize the epidemiology of neuropathic pain and the existing therapeutic drugs used for disease prevention and treatment. We also demonstrate how glycosides exhibit an antinociceptive effect on neuropathic pain in laboratory research and describe the antinociceptive mechanisms involved to facilitate the discovery of new drugs to improve the quality of life of patients experiencing neuropathic pain.
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Glicósidos/farmacología , Glicósidos/uso terapéutico , Neuralgia/tratamiento farmacológico , Analgésicos/farmacología , Analgésicos/uso terapéutico , Animales , Biomarcadores , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Regulación de la Expresión Génica/efectos de los fármacos , Glicósidos/química , Humanos , Activación del Canal Iónico/efectos de los fármacos , Ratones , Neuralgia/diagnóstico , Neuralgia/epidemiología , Neuralgia/etiología , Estrés Oxidativo/efectos de los fármacos , Manejo del Dolor , Relación Estructura-Actividad , Resultado del TratamientoRESUMEN
AIM: This study aims to evaluate the safety and analgesic efficacy of pre-mixed nitrous oxide/oxygen mixture treatment of pain induced by dressing change for perianal abscess. DESIGN: This protocol is a randomized, double-blind, placebo-controlled trial. METHODS: This study will be implemented in the Hospital of Traditional Chinese Medicine. Subjects enrolled in this study are hospitalized patients who suffered from moderate to severe pain due to dressing change after incision and drainage. Two hundred patients will be selected and randomly assigned to either an intervention or a control group. The intervention group will get routine pain treatment plus pre-mixed nitrous oxide/oxygen mixture treatment and the control group will be treated with routine pain management plus medical air treatment. All these patients, medical staff and investigators are blind to the nature of the gas in each cylinder, which is randomized. Data will be collected at baseline (T0), 5 min (T1) after the starting of intervention and 5 min post intervention (T2) for each group. The primary outcome is the level of pain relief at T1 and T2. The secondary outcomes cover physiological parameters, adverse events, satisfaction of patients and health professionals and the acceptance from patients. DISCUSSION: Results of this study will be discussed and the safety and effect of nitrous oxide/oxygen treatment of pain induced by dressing change will be proven. IMPACT: When the finding of this study has an active effect on the treatment of pain caused by dressing change, it may provide more options for nursing staff to choose nurse-led analgesia techniques and then improving the level and quality of pain care as well as patients' overall satisfaction with the Anorectal Department in China.
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Absceso , Óxido Nitroso , Absceso/terapia , Vendajes , China , Método Doble Ciego , Humanos , Oxígeno , Dolor/tratamiento farmacológico , Dolor/etiología , Dimensión del Dolor , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
To systematically review the effectiveness and safety of Pudilan Xiaoyan Oral Liquid on child upper respiratory infection and conduct Meta-analysis. We electronically retrieved databases, including PubMed, Web of Science, VIP, WanFang and CNKI, for published articles of randomized controlled trials(RCTs) of Pudilan Xiaoyan Oral Liquid on child upper respiratory infection from inception to April 2019. According to the inclusion and exclusion criteria, two reviewers independently screened out literatures, extracted data and assessed the risk of bias in included studies. Then, Meta-analysis were conducted by Stata 15.0 software. A total of 16 RCTs involving 1 924 patients with upper respiratory infection were included. The results of Meta-analysis showed that the improvement of clinical symptoms, such as fever subsided time(WMD=-3.66, 95%CI[-4.61,-2.72], P<0.001), cough time(WMD=-1.89, 95%CI[-2.51,-1.27], P<0.001), time of runny noses(WMD=-4.60, 95%CI[-5.85,-3.34], P<0.001) and time of sore throat(WMD=-2.62, 95%CI[-3.54,-1.70], P<0.001). Meanwhile, the results of Meta-analysis showed the improvement of laboratory indications, including TNF-α(WMD=-2.68, 95%CI[-2.98,-1.58], P<0.001) and IL-6(WMD=-2.26, 95%CI[-3.36,-2.36], P<0.01). The current evidence shows that Pudilan Xiaoyan Oral Liquid may significantly improve the effectiveness and safety. According to the limited quality of included studies, the above conclusion needs be to verified with more high-quality studies.
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Medicamentos Herbarios Chinos , Faringitis , Niño , Humanos , Factor de Necrosis Tumoral alfaRESUMEN
Endothelial cell death is linked to vascular diseases such as atherosclerosis and tissue ischemia. miRNA-17-92 (miR-17-92) is a multiple functional oncogenic miRNA cluster which plays vital roles in tumor angiogenesis and tissue development. However, its role in regulation of endothelial cell ferroptosis remains unclear. In this study, we revealed that miR-17-92 protects endothelial HUVEC cells from erastin-induced ferroptosis. miR-17-92 overexpression significantly reduced erastin-induced growth inhibition and ROS generation of HUVEC cells. Furthermore, Zinc lipoprotein A20, a validated target of miR-17-92, was identified as a novel regulator of endothelial cell ferroptosis. Lentivirus mediated A20 overexpression increased ROS generation and enhanced erastin-induced ferroptosis, whereas A20 knockdown inhibited erastin-induced ferroptosis. Mechanistic studies revealed that erastin-induced ferroptosis is associated with GPX4 downregulation and ACSL4 upregulation. miR-17-92 overexpression or A20 inhibition increased the ACSL4 expression in HUVEC cells. A20 was identified to directly with and regulate ACSL4 expression by immunoprecipitation. It suggests that the A20-ACSL4 axis plays important roles in erastin-induced endothelial ferroptosis. In conclusion, this study revealed a novel mechanism through which miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis.
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Coenzima A Ligasas/metabolismo , Citoprotección , Ferroptosis/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , MicroARNs/metabolismo , Piperazinas/farmacología , Transducción de Señal , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/metabolismo , Proliferación Celular/efectos de los fármacos , Citoprotección/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , MicroARNs/genética , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Acute pain is the most common complaint in Emergency Department (ED) admissions, and options for analgesia are limited. Nitrous oxide/oxygen possesses many properties showing it may be an ideal analgesic in the ED. OBJECTIVES: The aim of this study is to evaluate the safety and analgesic effect of the fixed nitrous oxide/oxygen mixture for trauma patients in the ED. METHODS: We enrolled 60 patients in this double-blind, randomized study. The treatment group received conventional pain treatment plus a mixture of 65% nitrous oxide/oxygen. The control group received the conventional pain treatment plus oxygen. Primary outcome was the reduction in pain intensity at 5 and 15 min after the start of intervention. Secondary outcomes include adverse events, physiological parameters, and satisfaction from both patients and health care professionals. RESULTS: Initial pain scores for the nitrous oxide/oxygen group (6.0 [5.0-8.0]) and the oxygen group (6.75 [5.0-9.0]) were comparable (p = 0.57). The mean numerical rating scale scores at 5 min were 3.4 ± 1.8 and 7.0 ± 1.8 for nitrous oxide/oxygen and oxygen, respectively (p < 0.01). The mean pain intensity at 15 min in the treatment group was 3.0 ± 1.9, compared with 6.3 ± 2.2 in the control group (p < 0.01). Both patients' (8.0 [7.0-9.0] vs. 4.0 [2.0-6.0], p < 0.01) and physicians' (8.5 [8.0-9.0] vs. 4.0 [3.0-6.0], p < 0.01) satisfaction scores in the treatment group were significantly higher than the oxygen group. No serious adverse events were observed. CONCLUSIONS: This study gives supporting evidence for the safety and effectiveness of using self-administered nitrous oxide/oxygen mixture in the ED for moderate-to-severe traumatic pain.
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Analgésicos/normas , Óxido Nitroso/farmacología , Oxígeno/farmacología , Manejo del Dolor/normas , Heridas y Lesiones/tratamiento farmacológico , Dolor Agudo/tratamiento farmacológico , Adulto , Analgésicos/uso terapéutico , Método Doble Ciego , Combinación de Medicamentos , Servicio de Urgencia en Hospital/organización & administración , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Óxido Nitroso/uso terapéutico , Oxígeno/uso terapéutico , Manejo del Dolor/métodos , Manejo del Dolor/estadística & datos numéricos , Dimensión del Dolor/métodos , Satisfacción del Paciente , Resultado del Tratamiento , Heridas y Lesiones/complicacionesRESUMEN
OBJECTIVE: This study aims to investigate the biological significance of heat shock protein (HSP70) in adaptation to high altitude hypoxia. METHODS: Ninety male SD rats were randomly divided into 10 groups: Acute plateau hypoxia group (group 5) and chronic high altitude hypoxia group (group 3), and control group (group 2).Changes in HSP gene and HSP protein expression in brain tissues of SD rats at different altitudes were determined by Western blot and conventional RT-PCR, while an optical and transmission electron microscope was used to observe the cell structure changes of animal brain tissues. RESULTS: HSP70 expression rapidly increased at high altitudes in SD rats under high-altitude hypoxia environments, and HSP70 increased with altitude. Morphological and structural damage in SD rats in each group increased with altitude. CONCLUSION: The rapid synthesis of HSP70 in heat shock response is beneficial for maintaining the normal physiological function of cells during hypoxia stress, and the amount of HSP70 production is positively correlated with hypoxia tolerance ability.
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Mal de Altura/patología , Encéfalo/ultraestructura , Proteínas HSP70 de Choque Térmico/metabolismo , Hipoxia/patología , Altitud , Animales , Western Blotting , Hipoxia/metabolismo , Masculino , Microscopía Electrónica de Transmisión , Distribución Aleatoria , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Testicular dysfunction is one of the serious secondary complications in diabetes. Lycium barbarum polysaccharide (LBP) has long been considered to possess a wide range of beneficial properties including antiaging, anticancer and reproductive-enhancing. Abnormal autophagy was reported to play a significant role in accelerating diabetic reproductive injury. However, the autophagy regulation mechanism of LBP on diabetic testicular dysfunction is incompletely understood. We investigate the protective effects of LBP on diabetic testicular dysfunction and its underlying mechanism with different approaches. Protective effects of LBP (40 mg/kg) on testicular functions were assessed through the use of sperm parameters, testosterone levels and hematoxylin and eosin staining. Antioxidant capacity and serum malondialdehyde levels were determined using assay kits. Immune intensity of Beclin-1 and LC3I in testes was detected by immunofluorescence staining. Western blot analysis was used to detect expressions of p-PI3K, Akt, p-Akt, Beclin-1, LC3I and LC3II proteins. Q-PCR was used to evaluate Beclin-1 and LC3I mRNA expressions in testis. Administration of LBP (40 mg/kg) considerably recovered testicular function, obviously improved testicular histopathologic structure and significantly increased antioxidant enzyme activities. Immunofluorescence staining showed that immune intensity of Beclin-1 and LC3I significantly decreased in the LBP 40 mg/kg group. The results of Q-PCR and western blot analysis showed that LBP 40 mg/kg significantly downregulated Beclin-1 and LC3I protein expressions upregulated p-PI3K and p-Akt protein expressions and decreased Beclin-1 and LC3I mRNA expressions compared with diabetic mice. In conclusion, inhibition of PI3K/Akt pathway-mediated testicular excessive autophagy may be a target for protective effects of LBP on diabetic testicular dysfunction.
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Autofagia , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/fisiopatología , Medicamentos Herbarios Chinos/uso terapéutico , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Testículo/patología , Testículo/fisiopatología , Animales , Autofagosomas/efectos de los fármacos , Autofagosomas/metabolismo , Autofagosomas/ultraestructura , Autofagia/efectos de los fármacos , Autofagia/genética , Proteínas Relacionadas con la Autofagia/genética , Proteínas Relacionadas con la Autofagia/metabolismo , Beclina-1/metabolismo , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/genética , Medicamentos Herbarios Chinos/farmacología , Masculino , Ratones Endogámicos ICR , Proteínas Asociadas a Microtúbulos/metabolismo , Estrés Oxidativo/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Espermatozoides/metabolismo , Testículo/efectos de los fármacos , Testosterona/sangreRESUMEN
Oxysophocarpine (OSC), an alkaloid isolated from Sophora flavescens Ait, has been traditionally used as a medicinal agent based on the observed pharmacological effects. In this study, the direct effect of OSC against neuronal injuries induced by oxygen and glucose deprivation (OGD) in neonatal rat primary-cultured hippocampal neurons and its mechanisms were investigated. Cultured hippocampal neurons, which were exposed to OGD for 2 h followed by a 24 h reoxygenation, were used as an in vitro model of ischemia and reperfusion. 2-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) assay were used to confirm neural damage and to further evaluate the protective effects of OSC. The concentration of intracellular-free calcium [Ca2+]i and mitochondrial membrane potential (MMP) were measured to determine the intracellular mechanisms and to further estimate the degree of neuronal damage. Changes in expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, p-ERK1/2, p-JNK1/2, and p-p38 MAPK were also observed in the in vitro model. It was shown that OSC (0.8, 2, or 5 µmol/L) significantly attenuated the increased absorbance of MTT, and the release of LDH manifests the neuronal damage by the OGD/R. Meanwhile, the pretreatment of the neurons during the reoxygenation period with OSC significantly increased MMP; it also inhibited [Ca2+]i the elevation in a dose-dependent manner. Furthermore, the pretreatment with OSC (0.8, 2, or 5 µmol/L) significantly down-regulated expressions of IL-1ß, TNF-α, p-ERK1/2, p-JNK1/2, and p-p38 MAPK in neonatal rat primary-cultured hippocampal neurons induced by OGD/R injury. In conclusion, OSC displays a protective effect on OGD-injured hippocampal neurons by attenuating expression of inflammatory factors via down-regulated the MAPK signaling pathway.
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Alcaloides/farmacología , Glucosa/deficiencia , Hipocampo/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Animales , Animales Recién Nacidos , Hipoxia de la Célula/efectos de los fármacos , Hipoxia de la Célula/fisiología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Femenino , Hipocampo/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Neuronas/metabolismo , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & controlRESUMEN
Neuropathic pain is an intractable disease with few definitive therapeutic options. Anethole (AN) has been confirmed to possess potent anti-inflammatory and neuroprotective properties, but its effect on neuropathic pain has not been reported. The present study was designed to investigate the antinociceptive effect of AN on chronic constriction injury (CCI)-induced neuropathic pain in mice. AN (125, 250, and 500 mg/kg) and pregabalin (40 mg/kg) were intragastric administered for 8 consecutive days from the 7th day post-surgery. Behavioral parameters were measured on different days, namely, 0, 7, 8, 10, 12, and 14, from CCI operation. Additionally, electrophysiological and histopathological changes were analyzed on the 14th day. Afterward, immunofluorescence and Western blot were utilized to examine the activation of glial cells and the expression of inflammatory cytokines, respectively. AN treatment of CCI mice considerably alleviated hyperalgesia and allodynia, ameliorated abnormal sciatic nerve conduction, and restored injured sciatic nerves in a dose-dependent manner. Furthermore, AN suppressed the activation of glial cells, down-regulated pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL-6, and IL-1ß), and up-regulated the anti-inflammatory cytokine (IL-10). These assays first indicated that AN exerted an antinociceptive effect on CCI-induced neuropathic pain, and might be attributed to the anti-inflammatory and neuroprotective activities of AN.
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Anisoles/uso terapéutico , Neuralgia/patología , Neuralgia/prevención & control , Fármacos Neuroprotectores/uso terapéutico , Neuropatía Ciática/tratamiento farmacológico , Neuropatía Ciática/patología , Derivados de Alilbenceno , Animales , Constricción , Masculino , Ratones , Ratones Endogámicos ICR , Neuralgia/etiología , Neuropatía Ciática/complicacionesRESUMEN
The aim of the study was to elucidate the therapeutic effects of Cytisine (CYT) on cerebral ischemia-reperfusion injury in mice. Male ICR mice were pretreated with reagents (drug), and then subjected to 2 h focal cerebral ischemia and 24 h reperfusion. Morphologically, the histopathological impairment were estimated by the TTC, HE and TUNEL staining. The expression of GluN2B-containing NMDA receptor, phosphorylation of extracellular regulated protein kinases, total ERK, phosphorylation of cAMP-response element binding protein and total CREB were determined by immunofluorescence and Western blot assay, respectively. The mRNA expression of NR2B, ERK and CREB were quantified by the real-time RT-PCR. CYT significantly diminished the infarct size and neuronal apoptosis. Additionally, it ameliorated histopathological lesion dramatically. CYT promoted the phosphorylation of ERK, CREB and their mRNA expression. In contrast, the expression of NR2B was suppressed in concomitant with the down-regulation of genes. The overall results thus far suggest that CYT confers the neuroprotection against cerebral I/R injury by regulating the NR2B-ERK/CREB signal pathway.
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Alcaloides/uso terapéutico , Isquemia Encefálica/prevención & control , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/fisiología , Sistema de Señalización de MAP Quinasas/fisiología , Receptores de N-Metil-D-Aspartato/fisiología , Daño por Reperfusión/prevención & control , Alcaloides/química , Alcaloides/farmacología , Animales , Azocinas/química , Azocinas/farmacología , Azocinas/uso terapéutico , Isquemia Encefálica/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos ICR , Neuroprotección/efectos de los fármacos , Neuroprotección/fisiología , Quinolizinas/química , Quinolizinas/farmacología , Quinolizinas/uso terapéutico , Daño por Reperfusión/patología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Breakthrough pain is an extremely painful symptom that impairs quality of life in cancer patients. It negatively impacts their emotional wellbeing, physical function, and mental health. The aim of this study is to use a qualitative methodology to examine the perception of cancer patients with breakthrough pain in the Northwest of China. METHODS: A semi-structured, face-to-face interview was conducted with nine cancer patients who experienced breakthrough pain; and a qualitative content analysis was performed. RESULTS: Five themes were generated: (1) sufferings from breakthrough cancer pain, (2) hopelessness and helplessness, (3) perception of breakthrough cancer pain and analgesia, (4) strong as a Chinese, and (5) support needed from health care system. CONCLUSION: Although certain traditional cultural worldviews increase patients' acceptance of pain, healthcare providers need proper treatment guidelines to improve the quality of cancer patient care in Northwest China. We recommend that healthcare workers and hospital managers place cancer pain management in higher priority. Relevant pain management education programs should be provided to both healthcare providers and patients to improve their knowledge in these area. Healthcare professionals need to establish a mutual communication channel between patients and healthcare workers to meet patients' needs during breakthrough pain episodes in order to improve pain management. Nevertheless, the government and the healthcare system need to recognize the importance and urgency of palliative care services.
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Dolor Irruptivo/complicaciones , Neoplasias/complicaciones , Adulto , Anciano , Dolor Irruptivo/etiología , Dolor Irruptivo/psicología , China , Femenino , Humanos , Entrevistas como Asunto/métodos , Masculino , Persona de Mediana Edad , Neoplasias/psicología , Manejo del Dolor/métodos , Manejo del Dolor/normas , Cuidados Paliativos/psicología , Investigación Cualitativa , Calidad de Vida/psicologíaRESUMEN
Lycium barbarum polysaccharides (LBP) have been reported to have a wide range of beneficial effects including neuroprotection, anti-aging and anticancer. However, the anti-inflammation mechanism of LBP on primary cultured rat hippocampal neurons injured by oxygen-glucose deprivation/reperfusion (OGD/RP) is incompletely understood. We investigate the neuroprotective effects of LBP on neonatal rat primary cultured hippocampal neurons injured by OGD/RP with different approaches: MTT assay was used to detect cell viability, lactate dehydrogenase leakage was used to detect neuronal damage, formation of reactive oxygen species was determined by using fluorescent probe DCFH-DA. Hoechst 33,342 staining and TUNEL staining were used to determine the cell apoptosis. JC-1 was used to evaluate loss of mitochondrial membrane potential (MMP). The fluorescence intensity of [Ca2+]i in hippocampal neurons was determined by laser scanning confocal microscopy. The expression of various apoptotic markers such as TLR4, IκB, IL-6 and NF-κB were investigated by RT-PCR and western blot analysis. Results from each approach demonstrated that LBP increased the cell abilities and decreased the cell morphologic impairment. Furthermore, LBP increased MMP but inhibited [Ca2+]i elevation and significantly suppressed overexpression of NF-κB, IL-6 TLR4 and increased IκB expression.
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Medicamentos Herbarios Chinos/farmacología , Hipocampo/citología , Neuronas/metabolismo , Animales , Apoptosis/efectos de los fármacos , Calcio/metabolismo , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Femenino , Glucosa/deficiencia , Interleucina-6/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , FN-kappa B/metabolismo , Neuronas/efectos de los fármacos , Oxígeno , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Reperfusión , Receptor Toll-Like 4/metabolismoRESUMEN
Epilepsy is one of the prevalent and major neurological disorders, and approximately one-third of the individuals with epilepsy experience seizures that do not respond well to available medications. We investigated whether oxysophocarpine (OSC) had anticonvulsant and neuroprotective property in the pilocarpine (PILO)-treated mice. Thirty minutes prior to the PILO injection, the mice were administrated with OSC (20, 40, and 80 mg/kg) once. Seizures and electroencephalography (EEG) were observed, and then the mice were killed for Nissl and Fluoro-jade B (FJB) staining. The oxidative stress was measured at 24 h after convulsion. Western blot analysis was used to examine the expressions of the Bax, Bcl-2, and Caspase-3. In this study, we found that pretreatment with OSC (40, 80 mg/kg) significantly delayed the onset of the first convulsion and status epilepticus (SE) and reduced the incidence of SE and mortality. Analysis of EEG recordings revealed that OSC (40, 80 mg/kg) significantly reduced epileptiform discharges. Furthermore, Nissl and FJB staining showed that OSC (40, 80 mg/kg) attenuated the neuronal cell loss and degeneration in hippocampus. In addition, OSC (40, 80 mg/kg) attenuated the changes in the levels of Malondialdehyde (MDA) and strengthened glutathione peroxidase and catalase activity in the hippocampus. Western blot analysis showed that OSC (40, 80 mg/kg) significantly decreased the expressions of Bax, Caspase-3 and increased the expression of Bcl-2. Collectively, the findings of this study indicated that OSC exerted anticonvulsant and neuroprotective effects on PILO-treated mice. The beneficial effects should encourage further studies to investigate OSC as an adjuvant in epilepsy, both to prevent seizures and to protect neurons in brain.
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Alcaloides/uso terapéutico , Anticonvulsivantes/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Pilocarpina/toxicidad , Convulsiones/metabolismo , Convulsiones/prevención & control , Factores de Edad , Alcaloides/farmacología , Animales , Anticonvulsivantes/farmacología , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Ratones Endogámicos ICR , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Convulsiones/inducido químicamente , Resultado del TratamientoRESUMEN
Increasing evidence demonstrates inflammation contributes to neuronal death following cerebral ischemia. Lycium barbarum polysaccharide (LBP) has been reported to prevent scopolamine-induced cognitive and memory deficits. We recently indicated that LBP exerts neuroprotective effect against focal cerebral ischemic injury in mice via attenuating the mitochondrial apoptosis pathway. The aim of this study was to investigate the neuroprotective effects of LBP against the behavioral dysfunction induced by focal cerebral ischemia injury in mice. Following 7 successive days of pretreatment with LBP (10, 20 and 40 mg/kg) and nimodipine (4 mg/kg) by intragastric gavage, mice were subjected to middle cerebral artery occlusion (MCAO). Following reperfusion, cerebral blood flows, the total power of the spontaneous EEG, and morphological changes were estimated. Learning and memory ability, and motor coordination were determined by Morris water maze task, rotarod and grip test. Western blot analysis, Real-Time fluorogenic PCR assays, and immunofluorescence staining were used to examine the expression of proinflammatory mediators and activation of microglia. The present study showed that LBP pretreatment significantly enhanced regional cortical blood flow and the total power of the spontaneous EEG, improved memory and motor coordination impairments, and inhibited over-activation of microglia and astrocytes after MCAO. Further study demonstrated LBP suppressed MCAO-induced activations of P65 NF-κB and P38 MAPK, and prevented up-regulations of proinflammatory mediators in hippocampus. Our data suggest that LBP can exert functional recovery of memory and motor coordination deficits and neuroprotective effect against cerebral ischemic injury in mice.
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Isquemia Encefálica/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Memoria/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Animales , Apoptosis/efectos de los fármacos , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/metabolismo , Isquemia Encefálica/metabolismo , Muerte Celular/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Infarto de la Arteria Cerebral Media/metabolismo , Masculino , Ratones , Microglía/efectos de los fármacos , Microglía/metabolismo , Neuronas/metabolismoRESUMEN
Diabetes-associated male sexual dysfunction and fertility impairments are both common clinical complications with limited therapeutic options; hence it seriously affects the quality of life of the patients, in particular, the patients of reproductive age. Lycium barbarum polysaccharide (LBP) has long being believed to maintain and to promote reproductive functions in the traditional medical practice in China. The current study was to investigate if LBP may contribute to recovery of male sexual dysfunction and fertility impairments in diabetic individuals. The effects of LBP on sexual behaviors and histological changes of testis were studied in the type-1 diabetes male mice induced by intra-peritoneal (i.p.) injection of streptozotocin (STZ). After oral administration of LBP (10, 20 or 40 mg/kg), sildenafil citrate (SC, 5 mg/kg) or saline for 62 consecutive days, the typical abnormal changes in the sperm parameters, in relative weight of reproductive organs and in morphology of testis were observed in diabetic mice. LBP treatment of the diabetic mice considerably reversed those changes and Johnsen's testicular score, serum testosterone (T), follicular stimulating hormone (FSH) and luteinizing hormone (LH) level were also increased to different degrees. Moreover, our data have also shown that a marked improvement in sexual behavior and fertility level after administration of LBP (40 mg/kg) compared to the diabetic group. These results suggested that LBP can exert functional recovery of male sexual dysfunction and fertility damages induced by diabetes in male mice, which is likely to be mediated through regulating the hypothalamus- pituitary-gonadal axis endocrine activity.
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Diabetes Mellitus Experimental/complicaciones , Medicamentos Herbarios Chinos/uso terapéutico , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Infertilidad Masculina/tratamiento farmacológico , Sustancias Protectoras/uso terapéutico , Conducta Sexual Animal/efectos de los fármacos , Disfunciones Sexuales Fisiológicas/tratamiento farmacológico , Animales , Diabetes Mellitus Experimental/sangre , Medicamentos Herbarios Chinos/farmacología , Hormona Folículo Estimulante/sangre , Infertilidad Masculina/sangre , Infertilidad Masculina/etiología , Hormona Luteinizante/sangre , Masculino , Ratones , Inhibidores de Fosfodiesterasa 5/farmacología , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Sustancias Protectoras/farmacología , Disfunciones Sexuales Fisiológicas/sangre , Disfunciones Sexuales Fisiológicas/etiología , Citrato de Sildenafil/farmacología , Citrato de Sildenafil/uso terapéutico , Testículo/efectos de los fármacos , Testosterona/sangreRESUMEN
Hypoxia provokes metabolism misbalance, mitochondrial dysfunction and oxidative stress in both human and animal cells. However, the mechanisms which hypoxia causes mitochondrial dysfunction and energy metabolism misbalance still remain unclear. In this study, we presented evidence that mitochondrial phosphatase Ptpmt1 is a hypoxia response molecule that regulates cell proliferation, survival and glucose metabolism in human erythroleukemia TF-1 cells. Exposure to hypoxia or DFO treatment results in upregulation of HIF1-α, HIF-2α and Ptpmt1. Only inhibition of HIF-2α by shRNA transduction reduces Ptpmt1 expression in TF-1 cells under hypoxia. Ptpmt1 inhibitor suppresses the growth and induces apoptosis of TF-1 cells. Furthermore, we demonstrated that Ptpmt1 inhibition reduces the Glut1 and Glut3 expression and decreases the glucose consumption in TF-1 cells. In additional, Ptpmt1 knockdown also results in the mitochondrial dysfunction determined by JC1 staining. These results delineate a key role for HIF-2α-induced Ptpmt1 upregulation in proliferation, survival and glucose metabolism of erythroleukemia cells. It is indicated that Ptpmt1 plays important roles in hypoxia-induced cell metabolism and mitochondrial dysfunction.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Glucosa/metabolismo , Leucemia Eritroblástica Aguda/metabolismo , Fosfohidrolasa PTEN/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Hipoxia de la Célula , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo/genética , Transportador de Glucosa de Tipo 1/genética , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 3/genética , Transportador de Glucosa de Tipo 3/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Leucemia Eritroblástica Aguda/patología , Fosfohidrolasa PTEN/genéticaRESUMEN
Chemotherapy drugs such as vincristine (VCR) can cause neuropathic pain, and there is still lack of ideal strategy to treat it. The current study was designed to investigate effect of matrine (MT) on VCR-induced neuropathic pain in animal model. VCR (75 µg/kg, i.p. for 10 consecutive days) was administered to induce painful neuropathy model in mice. MT (15, 30 and 60 mg/kg, i.p.) and pregabalin (10 mg/kg, i.p.) were administered for 11 consecutive days. Various tests were performed to assess the degree of pain at different days (1, 6, 11, 16, and 21). Von Frey hair, hot plate, cold-plate and paw pressure tests were conducted to assess the degree of mechanical allodynia, thermal hyperalgesia, cold allodynia and mechanical hyperalgesia in the hind paw respectively. The electrophysiological and histopathological changes were also analyzed. Furthermore, tissue malondialdehyde (MDA), total antioxidant capacity (T-AOC),superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total calcium (TCA), myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10) were measured to investigate possible involvement of MT in inflammation and oxidative stress. Administration of MT attenuated the VCR-induced behavioral alterations as well as electrophysiological and histopathological changes in a dose dependent manner. Further, MT also attenuated the VCR-induced oxidative stress (MDA, T-AOC, GSH-Px, SOD and TCA) and inflammation (MPO, TNF-α, IL-6 and IL-10). Taken together, MT ameliorated VCR-induced painful neuropathy, which might be attributed to neuroprotective effects by subsequent reduction in oxidative stress and anti-inflammatory actions.
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Alcaloides/farmacología , Neuralgia/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Quinolizinas/farmacología , Vincristina/farmacología , Animales , Antioxidantes/farmacología , Modelos Animales de Enfermedad , Ratones , Neuralgia/inducido químicamente , Estrés Oxidativo/efectos de los fármacos , Nervio Ciático/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , MatrinasRESUMEN
Ischemia stroke is the major cause of mortality and permanent neurological disability with little definitive therapeutic options. This cerebral ischemic injury leads to the oxidative stress and eventually cell death. We hypothesized that treatment of this condition with the trans-cinnamaldehyde(TC) could protect cells from ischemic and reperfusion injury. Oxygen and glucose deprivation/reperfusion (OGD/R) was used as an in vitro model of hypoxic ischemic injury in present study. MTT was used to evaluate the protective effects of TC. Next, we tested whether TC reduced the production of reactive oxygen species (ROS). Besides, experiments were performed to determine whether or not the mitochondrial membrane potential was affected. Furthermore, the inhibiters of NO and PI3 K were used to determine the initial mechanisms. TC treatment improved cell viability, reduced intracellular ROS, and increased MMP. Further, the inhibition of NO or PI3 K significantly reduced TC's protective effects. These findings suggest that TC might be a promising agent for ischemic stroke.
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Acroleína/análogos & derivados , Apoptosis/efectos de los fármacos , Glucosa/metabolismo , Estrés Oxidativo/efectos de los fármacos , Oxígeno/metabolismo , Daño por Reperfusión/metabolismo , Acroleína/farmacología , Animales , Células PC12 , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Gentiopicroside (Gent) is promising as an important protective secoiridoid compound against pain. The present study was designed to investigate whether administration of Gent would alleviate the expression of nociceptive behaviors and whether it would cause the relevant electrophysiological changes in a chronic constriction injury (CCI) model of neuropathic pain in mice. Gent was administered from the seventh day after surgery for 8 consecutive days. Behavioral parameters and sciatic functional index were assessed immediately before surgery and on days 7, 8, 10, 12, and 14 post-CCI, and electrophysiological activities of sciatic nerve were recorded immediately after the behavioral test on the last day. The present study has shown that administration of Gent (at a dose of 50 and 100 mg/kg) increased behavioral parameters from day 8 compared with the CCI-NS group. Electrophysiological data indicated that CCI caused a significant reduction in nerve conduction velocities in the sciatic nerves and the amplitudes of compound action potential, while Gent at a dose of 50 or 100 mg/kg caused a significant recovery of electrophysiological changes induced by CCI. Our data indicated that Gent has antinociceptive effects on neuropathic pain induced by CCI.
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Analgésicos/uso terapéutico , Fenómenos Electrofisiológicos/efectos de los fármacos , Glucósidos Iridoides/uso terapéutico , Locomoción/efectos de los fármacos , Neuralgia/tratamiento farmacológico , Neuropatía Ciática/tratamiento farmacológico , Analgésicos/farmacología , Animales , Constricción , Relación Dosis-Respuesta a Droga , Fenómenos Electrofisiológicos/fisiología , Glucósidos Iridoides/farmacología , Locomoción/fisiología , Masculino , Ratones , Ratones Endogámicos ICR , Neuralgia/fisiopatología , Neuropatía Ciática/fisiopatologíaRESUMEN
Oxysophocarpine is an alkaloid extracted from Sophora alopecuroides. We investigated the analgesic effect of oxysophocarpine on carrageenan-induced inflammatory pain in mice, in order to explore its possible mechanisms. Mouse ear swelling tests and carrageenan-induced paw edema tests were used to investigate the effects of oxysophocarpine on inflammatory pain in mice. Morphological changes on inflamed paw sections were measured by hematoxylin-eosin staining. The mRNA and protein expression of extracellular signal-regulated kinase, phosphorylation of extracellular signal-regulated kinase 1/2, cyclooxygenase-2, tumor necrosis factor α, interleukin-1 beta, interleukin-6 and prostaglandin E2 were investigated by real-time quantitative polymerase chain reaction, immunohistochemistry, western-blot and enzyme-linked immunosorbent assay. In our results, oxysophocarpine shows a significant anti-inflammatory effect in the mouse ear swelling test. Oxysophocarpine also significantly reduced the paw edema volume and improved mechanical allodynia threshold value on carrageenan-induced inflammatory pain, as well as relieved paw tissues inflammatory damage and reduced the numbers of neutrophils in mice. Oxysophocarpine significantly suppressed over-expression of cyclooxygenase-2, tumor necrosis factor α, interleukin-1 beta, interleukin-6 and prostaglandin E2, and inhibited the over-phosphorylation of extracellular signal-regulated kinase 1/2. Based on these findings we propose that oxysophocarpine attenuates inflammatory pain by suppressing the levels of phosphorylation of extracellular signal-regulated kinase 1/2, cyclooxygenase-2, prostaglandin E2, tumor necrosis factor α, interleukin-1 beta and interleukin-6.