RESUMEN
Diosgenin is a sapogenin with antidiabetic, antioxidant, and anti-inflammatory properties. The current study investigated whether diosgenin could ameliorate carbon tetrachloride (CCL4)-induced liver injury. To cause liver injury, CCL4 was injected intraperitoneally twice a week for 8 weeks. Daily oral administration of diosgenin at doses of 20, 40, and 80 mg/kg was started one day before CCL4 injection and continued for 8 weeks. Finally, serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and also albumin were assessed. Catalase and superoxide dismutase (SOD) activities in addition to glutathione (GSH) and malondialdehyde (MDA) levels were also quantified in the liver homogenate and routine histological evaluation was also conducted. Elevated serum levels of liver enzymes and decreased serum level of albumin caused by CCL4 were significantly restored following diosgenin administration at doses of 40 and 80 mg/kg. Long-term administration of CCL4 increased inflammatory and apoptotic factors such as IL-1ß, caspase 3, TNF-α, and IL-6 and decreased SOD and catalase activities as well as GSH level in liver homogenates; while MDA level was increased. Treatment with diosgenin increased SOD and catalase activities and GSH levels in the liver of injured animals. In addition, liver MDA, IL-1ß, caspase 3, TNF-α, and IL-6 level or activity decreased by diosgenin treatment. Additionally, diosgenin aptly prevented aberrant liver histological changes. According to obtained results, diosgenin can dose-dependently diminish CCl4-induced liver functional deficits and histological changes in a dose-dependent manner, possibly due to its antioxidant and anti-inflammation properties, and its beneficial effect is comparable to known hepatoprotective agent silymarin.
Asunto(s)
Antioxidantes , Enfermedad Hepática Inducida por Sustancias y Drogas , Ratones , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Tetracloruro de Carbono/toxicidad , Catalasa , Caspasa 3 , Factor de Necrosis Tumoral alfa , Interleucina-6 , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Hígado , Glutatión , Antiinflamatorios/farmacología , Superóxido Dismutasa , Albúminas/farmacología , Alanina TransaminasaRESUMEN
BACKGROUND: Sepsis-associated acute kidney injury (AKI) is highlighted by high incidence of mortality and morbidity. Scutellarin is a flavone extracted from certain medicinal plants with anti-inflammatory and anti-oxidative properties. This research study was done to investigate the beneficial effect of scutellarin on lipopolysaccharide (LPS) murine model of AKI. MATERIALS AND METHODS: Five groups of mice were used including control (without LPS injection), LPS group (LPS injection, 10 mg/kg), and LPS + Scutellarin25, 50, and/or 100 groups (receiving scutellarin orally at different doses of 25, 50, or 100 mg/kg before LPS injection). RESULTS: Scutellarin pretreatment effectively lowered kidney function markers (BUN, creatinine, and cystatin C), improved superoxide dismutase (SOD) besides enhancement of level, and/or gene expression for nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) and also reduced oxidative stress factors including reactive oxygen species (ROS) and malondialdehyde (MDA). In addition, scutellarin reduced tissue level and/or gene expression of inflammatory markers comprising toll-like receptor 4 (TLR4), nuclear factor-kappaB (NF-κB), and tumor necrosis factor α (TNF-α) and properly raised anti-inflammatory factor IL-10. Moreover, scutellarin enhanced mitochondrial membrane potential (MMP) and attenuated histopathological changes in renal tissue subsequent to LPS challenge. Beneficial effects of scutellarin was associated with improvement of gene expression regarding peroxisome proliferator-activated receptor gamma (PPARγ) and its coactivator PGC-1α as specific markers of mitochondrial biogenesis. CONCLUSION: These results indicate that scutellarin could protect against LPS-provoked AKI through restraining inflammation and oxidative stress and maintenance of mitochondrial health and biogenesis which is partly mediated through its regulation of Nrf2/PPAR-γ/PGC-1α/NF-kB/TLR4.
Asunto(s)
Lesión Renal Aguda , Lipopolisacáridos , Ratones , Animales , Lipopolisacáridos/toxicidad , Receptor Toll-Like 4/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , FN-kappa B/metabolismo , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Mitocondrias/metabolismoRESUMEN
BACKGROUND: Sepsis-associated acute kidney injury (AKI) accompanies a higher mortality in intensive care patients. High-dose lipopolysaccharides (LPS) as an endotoxin is usually used to model AKI in rodents. Lycopene is a fat-soluble carotenoid with proved protective effects in different condition. Rationale and purpose of the study. This research work was designed to assess the effect of lycopene in LPS murine AKI. METHODS AND RESULTS: LPS was injected (intraperitoneally) at 10 mg/kg to induce AKI and lycopene was given (orally) at 5 or 20 mg/kg. Pretreatment of LPS group with lycopene (20 mg/kg) lowered serum BUN, creatinine, and cystatin C and alleviated renal indices of oxidative stress consisting of malondialdehyde and reactive oxygen species and elevated level of catalase activity, superoxide dismutase activity, and glutathione peroxidase activity. In addition, lycopene (20 mg/kg) attenuated renal neutrophil infiltration and reduced renal inflammation, improved mitochondrial membrane potential, and increased gene expression for PGC1-α as a key regulator of mitochondrial biogenesis. In addition, lycopene appropriately reduced level and gene expression of inflammation-related transcription factors including NF-kB and TLR4 and improved level and gene expression of Nrf2 as an important transcription factor related to antioxidant system. Besides, lycopene prevented histopathological changes following LPS in periodic acid-Schiff staining. CONCLUSIONS: Collectively, this study revealed that lycopene has favorable effects by means of amelioration of mitochondrial dysfunction, oxidative stress, and inflammation and accordingly could protect against LPS-induced AKI.
Asunto(s)
Lesión Renal Aguda , Lipopolisacáridos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Animales , Antioxidantes/metabolismo , Modelos Animales de Enfermedad , Inflamación/metabolismo , Lipopolisacáridos/metabolismo , Lipopolisacáridos/toxicidad , Licopeno/metabolismo , Licopeno/farmacología , Ratones , Mitocondrias/metabolismo , Estrés OxidativoRESUMEN
Sinomenine is the main bioactive ingredient of the medicinal plant Sinomenium acutum with neuroprotective potential. This study was designed to assess beneficial effect of sinomenine in alleviation of trimethyltin (TMT)-induced cognitive dysfunction. TMT was administered i.p. (8 mg/kg, once) and sinomenine was daily given p.o. 1 h after TMT for 3 weeks at doses of 25 or 100 mg/kg. Cognitive performance was assessed in various behavioral tests. In addition, oxidative stress- and inflammation-associated factors were measured and histochemical evaluation of the hippocampus was conducted. Sinomenine at a dose of 100 mg/kg significantly and partially increased discrimination index in novel object recognition (NOR), improved alternation in short-term Y maze, increased step-through latency in passive avoidance paradigm, and also reduced probe trial errors and latency in the Barnes maze task. Moreover, sinomenine somewhat prevented inappropriate hippocampal changes of malondialdehyde (MDA), reactive oxygen species (ROS), protein carbonyl, nitrite, superoxide dismutase (SOD), tumor necrosis factor α (TNFα), interleukin 6 (IL 6), acetylcholinesterase (AChE) activity, beta secretase 1 (BACE 1) activity, and mitochondrial membrane potential (MMP) with no significant effect on glutathione (GSH), catalase, glutathione reductase, glutathione peroxidase, and myeloperoxidase (MPO). In addition, lower reactivity (IRA) for glial fibrillary acidic protein (GFAP) as an index of astrocyte activity was observed and loss of CA1 pyramidal neurons was attenuated following sinomenine treatment. This study demonstrated that sinomenine could lessen TMT-induced cognitive dysfunction which is partly due to its attenuation of hippocampal oxidative stress and neuroinflammation.
Asunto(s)
Disfunción Cognitiva , Fármacos Neuroprotectores , Acetilcolinesterasa/metabolismo , Animales , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , Glutatión/metabolismo , Hipocampo/metabolismo , Aprendizaje por Laberinto , Morfinanos , Enfermedades Neuroinflamatorias , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo , Ratas , Ratas Wistar , Compuestos de TrimetilestañoRESUMEN
Acetaminophen (APAP)-induced acute liver injury (ALI) is the principal cause of acute liver failure (ALF) in some countries including the United States and with few available treatments. Isorhamnetin is a bioflavonoid that is found in medicinal plants like Hippophae rhamnoides L. and Ginkgo biloba L. with promising potential to regulate inflammatory responses. In this study, we evaluated the possible effect of isorhamnetin in prevention of APAP-induced ALI and analyzed further the involvement of oxidative stress and inflammation-associated factors. Male C57BL/6 mice were given isorhamnetin (25 or 100 mg/kg b.w., p.o.) three times at 48, 24, and 1 h before APAP administration (300 mg/kg b.w., i.p.). Functional indicators of liver injury were measured as well as analysis of oxidative stress- and inflammation-associated indices and liver histopathology was also conducted. Isorhamnetin at the higher dose of 100 mg/kg significantly lowered serum levels of ALT, ALP, and AST in addition to reduction of ROS, TBARS, IL-6, TNFα, NF-kB, NLRP3, caspase 1, and MPO and significantly prevented reduction of GSH, SOD activity, sirtuin 1, and Nrf2. Additionally, isorhamnetin alleviated pathological changes of the liver tissue and suitably reversed NF-kB and Nrf2 immunoreactivity. These findings show protective effect of isorhamnetin against acetaminophen-induced liver injury through reducing oxidative stress, inflammation, and pyroptosis which is attributed to its regulation of NF-kB, Nrf2, NLRP3, and sirtuin 1.
Asunto(s)
Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas , Acetaminofén/toxicidad , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Inflamación/tratamiento farmacológico , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estrés Oxidativo , Quercetina/análogos & derivados , Sirtuina 1/metabolismoRESUMEN
Multiple sclerosis (MS) is a chronic and inflammatory disorder of the central nervous system with autoimmune nature that is typified by varying degrees of demyelination and axonal damage. Paeonol is an active ingredient in some medicinal plants with anti-inflammatory and neuroprotective property. This study was conducted to reveal whether paeonol can alleviate hippocampal demyelination and cognitive deficits in cuprizone-induced murine model of demyelination as a model of MS. C57BL/6 mice received oral cuprizone (400 mg/kg) for 6 weeks, and paeonol was administered p.o. at two doses of 25 or 100 mg/kg, starting from the second week post-cuprizone for 5 weeks. After assessment of learning and memory in different tasks, oxidative stress and inflammation were evaluated besides immunohistochemical assessment of hippocampal myelin basic protein (MBP). Paeonol (100 mg/kg) properly ameliorated cognitive deficits in Y maze, novel object discrimination (NOD) test, and Barnes maze with no significant improvement of performance in passive avoidance task. In addition, paeonol treatment at the higher dose was also associated with partial restoration of hippocampal level of oxidative stress and inflammatory markers including MDA, ROS, GSH, SOD, catalase, NF-kB, and TNF. Besides, paeonol improved MMP as an index of mitochondrial integrity and health and reduced MPO as a factor of neutrophil infiltration. Furthermore, paeonol treatment prevented hippocampal MBP immunoreactivity, indicating its prevention of demyelination. In conclusion, the current study showed the preventive effect of paeonol against cuprizone-induced demyelination and cognitive deficits through reversing most oxidative stress- and inflammation-related parameters in addition to its improvement of mitochondrial health.
Asunto(s)
Cuprizona , Esclerosis Múltiple , Acetofenonas , Animales , Cognición , Cuprizona/toxicidad , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Ratones , Ratones Endogámicos C57BL , Esclerosis Múltiple/tratamiento farmacológico , Estrés OxidativoRESUMEN
Intracerebroventricular (ICV) microinjection of diabetogenic drug streptozotocin (STZ) in rodents consistently produces a model of sporadic Alzheimer's disease (sAD) which is characterized by tau pathology and concomitant cognitive decline, insulin resistance, neuroinflammation, oxidative stress, and mitochondrial malfunction. Paeonol is an active phenolic component in some medicinal plants like Cortex Moutan with neuroprotective efficacy via exerting anti-inflammatory and anti-oxidative effects. This study was conducted to assess beneficial effect of paeonol in amelioration of cognitive deficits in ICV STZ rat model of sAD. STZ (3 mg/kg) was microinjected into the lateral ventricles on days 0 and 2, and paeonol was given p.o. at two doses of 25 (low) or 100 (high) mg/kg from day 0 (post-surgery) till day 24 post-STZ. Cognitive performance was evaluated in different tasks, and oxidative stress- and inflammation-related parameters were measured in addition to immunohistochemical assessment of glial fibrillary acidic protein (GFAP) as a marker of astrocytes. Paeonol at the higher dose ameliorated cognitive deficits in Barnes maze, novel object recognition (NOR) task, Y maze, and passive avoidance test. In addition, paeonol partially reversed hippocampal malondialdehyde (MDA), reactive oxygen species (ROS), total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase, glutathione reductase, tumor necrosis factor α (TNFα), interleukin 6 (IL-6), mitochondrial membrane potential (MMP), myeloperoxidase (MPO), and acetylcholinesterase (AChE) activity. Paeonol treatment was also associated with lower hippocampal immunoreactivity for GFAP. This study showed that paeonol can alleviate cognitive disturbances in ICV STZ rat model of sAD via ameliorating neuroinflammation, oxidative stress, mitochondrial dysfunction, and also through its attenuation of astrogliosis.
Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Acetofenonas , Acetilcolinesterasa/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Animales , Cognición , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Aprendizaje por Laberinto , Ratones , Mitocondrias/metabolismo , Estrés Oxidativo , Ratas , Ratas Wistar , Estreptozocina/toxicidadRESUMEN
Depression is one of the most common mental health disorders and it is generally characterized by negative mood. Although electroconvulsive therapy (ECT) is an effective treatment for depression, however, it can cause cognitive deficit. Hesperetin, an active ingredient in citrus peels, has antioxidant and neuroprotective properties. In this study, we evaluated the effect of hesperetin on memory impairment induced by ECT in a reserpine-induced depression model in male rat. For this purpose, 105 male rats weighing 230-250 g were randomly divided into control and reserpine-treated groups. The reserpine-treated animals were subdivided into: Reserpine, Hesperetin (10 and 20 mg/kg), ECT and ECT+Hesperetin (10 and 20 mg/kg). After taking the drugs, the effect of hesperetin was evaluated through behavioral NORT, Y Maze, FST, SPT and also via assessment of hippocampal brain-derived neurotrophic factor (BDNF) and oxidative stress biomarkers i.e., MDA, SOD and GSH. As a result, our biochemical studies showed a significant decrease of MDA in groups treated with ECT+Hesperetin as compared to ECT and hesperetin groups (P < 0.001) and a marked increase in SOD, GSH and BDNF in ECT+Hesperetin 20 group as compared to other groups (p < 0.05). Also, the results of behavioral tests revealed that treatment with hesperetin can increase the novel object recognition index and alternation behaviors in Y maze test as compared to the groups treated with hesperetin or ECT (p < 0.05). These results suggest that co-administration of hesperetin with ECT is effective for improvement of cognitive function and can alleviate ECT-induced memory impairment in reserpine-treated rats.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Depresión/tratamiento farmacológico , Terapia Electroconvulsiva/efectos adversos , Hesperidina/uso terapéutico , Trastornos de la Memoria/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Inhibidores de Captación Adrenérgica/toxicidad , Animales , Depresión/metabolismo , Depresión/psicología , Modelos Animales de Enfermedad , Hesperidina/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Trastornos de la Memoria/etiología , Trastornos de la Memoria/metabolismo , Estrés Oxidativo/fisiología , Ratas , Ratas Wistar , Reserpina/toxicidadRESUMEN
BACKGROUND: The medicinal plant Myrtus communis L. (Myrtle) has properties, including anti-inflammatory and wound healing in Persian Medicine. OBJECTIVE: The objective of this study was to explore the wound healing potential of the local application of a gel containing aqueous extract of the plant berry in streptozotocin (STZ)-induced diabetic rats. METHODS: Seven days after diabetes establishment, full-thickness excision skin wounds were made in normal and diabetic rats where treated groups received topical application of a gel containing 6% aqueous extract of myrtle berries for 3 weeks. The rate of wound healing and the level of epidermal and dermal maturation in the wound tissue were determined. RESULTS: The results showed that after 3 and 7 days of wound injury, the gel significantly improved wound healing by accelerating epidermal and dermal maturation in diabetic rats with no significant effect in the control group. However, the wounds of all groups almost completely healed after 3 weeks. CONCLUSION: These results demonstrate that aqueous extract of myrtle possesses a definite wound healing potential in diabetic conditions. The present findings may suggest the use of topical myrtle berries aqueous extract gel 6% to treat and manage intractable diabetic wounds.
Asunto(s)
Diabetes Mellitus Experimental/complicaciones , Pie Diabético/tratamiento farmacológico , Myrtus/química , Extractos Vegetales/administración & dosificación , Cicatrización de Heridas/efectos de los fármacos , Administración Cutánea , Animales , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Pie Diabético/etiología , Pie Diabético/patología , Frutas/química , Geles , Humanos , Masculino , Extractos Vegetales/aislamiento & purificación , Ratas , Piel/efectos de los fármacos , Piel/patología , Estreptozocina/administración & dosificación , Estreptozocina/toxicidadRESUMEN
Multiple sclerosis (MS) is known as a chronic neuroinflammatory disorder typified by an immune-mediated demyelination process with ensuing axonal damage and loss. Sinomenine is a natural alkaloid with different therapeutic benefits, including anti-inflammatory and immunosuppressive activities. In this study, possible beneficial effects of sinomenine in an MOG-induced model of MS were determined. Sinomenine was given to MOG35-55-immunized C57BL/6 mice at doses of 25 or 100 mg/kg/day after onset of MS clinical signs till day 30 post-immunization. Analyzed data showed that sinomenine reduces severity of the clinical signs and to some extent decreases tissue level of pro-inflammatory cytokines IL-1ß, IL-6, IL-18, TNFα, IL-17A, and increases level of anti-inflammatory IL-10. In addition, sinomenine successfully attenuated tissue levels of inflammasome NLRP3, ASC, and caspase 1 besides its reduction of intensity of neuroinflammation, demyelination, and axonal damage and loss in lumbar spinal cord specimens. Furthermore, immunoreactivity for MBP decreased and increased for GFAP and Iba1 after MOG-immunization, which was in part reversed upon sinomenine administration. Overall, sinomenine decreases EAE severity, which is attributed to its alleviation of microglial and astrocytic mobilization, demyelination, and axonal damage along with its suppression of neuroinflammation, and its beneficial effect is also associated with its inhibitory effects on inflammasome and pyroptotic pathways; this may be of potential benefit for the primary progressive phenotype of MS.
Asunto(s)
Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Inflamasomas/antagonistas & inhibidores , Morfinanos/uso terapéutico , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Animales , Astrocitos/efectos de los fármacos , Peso Corporal , Citocinas/análisis , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Femenino , Ratones , Ratones Endogámicos C57BL , Microglía/efectos de los fármacos , Morfinanos/administración & dosificación , Morfinanos/farmacología , Glicoproteína Mielina-Oligodendrócito/inmunología , Glicoproteína Mielina-Oligodendrócito/toxicidad , Fragmentos de Péptidos/inmunología , Fragmentos de Péptidos/toxicidad , Piroptosis/efectos de los fármacos , Distribución Aleatoria , Organismos Libres de Patógenos Específicos , Médula Espinal/químicaRESUMEN
Alzheimer's disease (AD) is the most prevalent neurodegenerative amyloid disorder with progressive deterioration of cognitive and memory skills. Despite many efforts, no decisive therapy yet exists for AD. Safranal is the active constituent of saffron essential oil with antioxidant, anti-inflammatory, and anti-apoptotic properties. In this study, the possible beneficial effect of safranal on cognitive deficits was evaluated in a rat model of AD induced by intrahippocampal amyloid beta (Aß1-40). Safranal was daily given p.o. (0.025, 0.1, and 0.2 ml/kg) post-surgery for 1 week and finally learning and memory were evaluated in addition to assessment of the involvement of oxidative stress, inflammation, and apoptosis. Findings showed that safranal treatment of amyloid ß-microinjected rats dose-dependently improved cognition in Y-maze, novel-object discrimination, passive avoidance, and 8-arm radial arm maze tasks. Besides, safranal attenuated hippocampal level of malondialdehyde (MDA), reactive oxygen species (ROS), protein carbonyl, interleukin 1ß (IL-1ß), interleukin 6 (IL-6), tumor necrosis factor α (TNFα), nuclear factor-kappa B (NF-kB), apoptotic biomarkers including caspase 3 and DNA fragmentation, glial fibrillary acidic protein (GFAP), myeloperoxidase (MPO), and acetylcholinesterase (AChE) activity and improved superoxide dismutase (SOD) activity and mitochondrial membrane potential (MMP) with no significant effect on nitrite, catalase activity, and glutathione (GSH). Furthermore, safranal prevented CA1 neuronal loss due to amyloid ß1-40. In summary, safranal treatment of intrahippocampal amyloid beta1-40-microinjected rats could prevent learning and memory decline via neuronal protection and at a molecular level through amelioration of apoptosis, oxidative stress, inflammation, cholinesterase activity, neutrophil infiltration, and also by preservation of mitochondrial integrity.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Trastornos del Conocimiento/tratamiento farmacológico , Ciclohexenos/uso terapéutico , Hipocampo/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Terpenos/uso terapéutico , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides , Animales , Apoptosis/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/metabolismo , Ciclohexenos/farmacología , Fragmentación del ADN/efectos de los fármacos , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Inflamación/metabolismo , Masculino , Malondialdehído/metabolismo , Fragmentos de Péptidos , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Terpenos/farmacologíaRESUMEN
Sepsis is a serious and life-threatening medical condition with a higher rate of patients' morbidity and mortality and with complications such as acute kidney injury (AKI). S-allyl cysteine (SAC) is the active constituent of the medicinal plant garlic (Allium sativum) with multiple beneficial effects including anti-inflammatory and antioxidant properties. In this research, we tried to determine the protective effect of SAC pretreatment in a mouse model of AKI. To induce AKI, lipopolysaccharide (LPS) was injected once (10â¯mg/kg, i.p.) and SAC was administered at doses of 25, 50, or 100â¯mg/kg (p.o.) 1â¯h before LPS. Treatment of LPS-challenged C56BL/6 animals with SAC lowered serum level of creatinine and blood urea nitrogen (BUN), partially restored renal oxidative stress-related biomarkers including malondialdehyde (MDA), glutathione (GSH), and activity of superoxide dismutase (SOD) and catalase in addition to improvement of mitochondrial membrane potential (MMP). Furthermore, SAC was capable to bring renal nuclear factor-kappaB (NF-κB), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX2), tumor necrosis factor α (TNFα), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), Annexin V, and DNA fragmentation partially back to their control levels. Additionally, SAC pretreatment was capable to exert a protective effect, as shown histologically by lower tubular injury and pathologic changes in the kidney. In summary, SAC is capable to alleviate LPS-induced AKI through mitigation of renal oxidative stress, inflammation, and apoptosis in addition to preservation of mitochondrial integrity and its favorable effect exhibits a dose-dependent pattern.
Asunto(s)
Lesión Renal Aguda/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Cisteína/análogos & derivados , Riñón/efectos de los fármacos , Sepsis/tratamiento farmacológico , Animales , Apoptosis , Creatinina/sangre , Cisteína/uso terapéutico , Modelos Animales de Enfermedad , Ajo/inmunología , Humanos , Inflamación , Riñón/patología , Lipopolisacáridos/inmunología , Masculino , Malondialdehído/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo , Transducción de SeñalRESUMEN
Systemic lipopolysaccharide (LPS) triggers neuroinflammation with consequent development of behavioral and cognitive deficits. Neuroinflammation plays a crucial role in the pathogenesis of neurodegenerative disorders including Alzheimer's disease (AD). Berberine is an isoquinoline alkaloid in Berberis genus with antioxidant and anti-inflammatory property and protective effects in neurodegenerative disorders. In this research, beneficial effect of this alkaloid against LPS-induced cognitive decline was assessed in the adult male rats. LPS was intraperitoneally administered at a dose of 1 mg/kg to induce neuroinflammation and berberine was given via gavage at doses of 10 or 50 mg/kg, one h after LPS, for 7 days. Treatment of LPS group with berberine at a dose of 50 mg/kg (but not at a dose of 10 mg/kg) improved spatial recognition memory in Y maze, performance in novel object recognition task (NORT), and prevented learning and memory dysfunction in passive avoidance tasks. Furthermore, berberine lowered hippocampal activity of acetylcholinesterase (AChE), malondialdehyde (MDA), protein carbonyl, activity of caspase 3, and DNA fragmentation and improved antioxidant capacity through enhancing glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase, and glutathione (GSH). Besides, berberine attenuated inflammation-related indices, as was evident by lower levels of nuclear factor-kappa B (NF-κB), toll-like receptor 4 (TLR4), tumor necrosis factor α (TNFα), and interleukin 6 (IL-6). Berberine also appropriately restored hippocampal 3-nitrotyrosine (3-NT), cyclooxygenase 2 (Cox 2), glial fibrillary acidic protein (GFAP), sirtuin 1, and mitogen-activated protein kinase (p38 MAPK) with no significant alteration of brain-derived neurotrophic factor (BDNF). In summary, berberine could partially ameliorate LPS-induced cognitive deficits via partial suppression of apoptotic cascade, neuroinflammation, oxido-nitrosative stress, AChE, MAPK, and restoration of sirtuin 1.
Asunto(s)
Antioxidantes/uso terapéutico , Berberina/uso terapéutico , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Memoria Espacial/efectos de los fármacos , Acetilcolinesterasa/metabolismo , Animales , Antioxidantes/farmacología , Berberina/farmacología , Fragmentación del ADN/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Inflamación/metabolismo , Lipopolisacáridos , Masculino , Malondialdehído/metabolismo , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/metabolismo , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most common phenotype of dementia. Trigonelline is an alkaloid found in medicinal plants such as fenugreek seeds and coffee beans with neuroprotective potential and according to existing evidences, a favorable agent for treatment of neurodegenerative disorders. In this study, the possible protective effect of trigonelline against intracerebral Aß(1-40) as a model of AD in the rat was investigated. For induction of AD, aggregated A(1-40) (10 µg/2 íl for each side) was bilaterally microinjected into the hippocampal CA1 area. Trigonelline was administered p.o. at a dose of 100 mg/kg. The results showed that trigonelline pretreatment of Aß-microinjected rats significantly improves spatial recognition memory in Y maze and performance in novel object recognition (NOR) task, mitigates hippocampal malondialdehyde (MDA), protein carbonyl, lactate dehydrogenase (LDH), and improves mitochondrial membrane potential (MMP), glutathione (GSH), and superoxide dismutase (SOD) with no significant change of catalase activity, nitrite level, caspase 3 activity, and DNA fragmentation. Additionally, trigonelline ameliorated hippocampal levels of glial fibrillary acidic protein (GFAP), S100b, cyclooxygenase 2 (Cox2), tumor necrosis factor α (TNFα), and interleukin 6 (IL-6) with no significant alteration of inducible nitric oxide synthase (iNOS). In addition, trigonelline pretreatment prevented loss of hippocampal CA1 neurons in Aß-microinjected group. Therefore, our results suggest that trigonelline pretreatment in Aß model of AD could improve cognition and is capable to alleviate neuronal loss through suppressing oxidative stress, astrocyte activity, and inflammation and also through preservation of mitochondrial integrity.
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Alcaloides/farmacología , Enfermedad de Alzheimer/prevención & control , Péptidos beta-Amiloides/farmacología , Antioxidantes/farmacología , Hipocampo/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Alcaloides/uso terapéutico , Enfermedad de Alzheimer/metabolismo , Animales , Antioxidantes/uso terapéutico , Citocinas/metabolismo , Modelos Animales de Enfermedad , Glutatión/metabolismo , Hipocampo/metabolismo , Masculino , Malondialdehído/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Ratas , Ratas Wistar , Memoria Espacial/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
Brain inflammation is associated with cognitive dysfunction, especially in elderly. Trigonelline is a plant alkaloid and a major component of coffee and fenugreek with anti-diabetic, antioxidant, anti-inflammatory, and neuroprotective effects. In this study, the beneficial effect of trigonelline against lipopolysaccharide (LPS)-induced cognitive decline was assessed in the rat. LPS was injected i.p. at a dose of 500⯵g/kg to induce neuroinflammation and trigonelline was administered p.o. at doses of 20, 40, or 80â¯mg/kg/day 1â¯h after LPS that continued for one week. Trigonelline-treated LPS-challenged rats showed improved spatial recognition memory in Y maze, discrimination ratio in novel object discrimination test, and retention and recall in passive avoidance paradigm. Additionally, trigonelline lowered hippocampal malondialdehyde (MDA) and acetylcholinesterase (AChE) activity and improved superoxide dismutase (SOD), catalase, and glutathione (GSH). Furthermore, trigonelline depressed hippocampal nuclear factor-kappaB (NF-κB), toll-like receptor 4 (TLR4), and tumor necrosis factor α (TNF α) in LPS-challenged rats. All of the effects of trigonelline followed a dose-dependent pattern and in some aspects, it acted even better than the routinely-used anti-inflammatory drug dexamethasone. Collectively, trigonelline is capable to diminish LPS-induced cognitive decline via suppression of hippocampal oxidative stress and inflammation and appropriate modulation of NF-κB/TLR4 and AChE activity.
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Alcaloides/uso terapéutico , Antioxidantes/uso terapéutico , Encéfalo/efectos de los fármacos , Discapacidades para el Aprendizaje/tratamiento farmacológico , Trastornos de la Memoria/tratamiento farmacológico , Inflamación Neurogénica/tratamiento farmacológico , Acetilcolinesterasa/metabolismo , Anciano , Animales , Encéfalo/inmunología , Encéfalo/patología , Humanos , Discapacidades para el Aprendizaje/inducido químicamente , Lipopolisacáridos/inmunología , Masculino , Malondialdehído/metabolismo , Trastornos de la Memoria/inducido químicamente , FN-kappa B/metabolismo , Inflamación Neurogénica/inducido químicamente , Estrés Oxidativo/efectos de los fármacos , Reconocimiento Visual de Modelos/efectos de los fármacos , Ratas , Ratas Wistar , Transducción de Señal , Receptor Toll-Like 4/metabolismoRESUMEN
Multiple sclerosis (MS) is a deleterious autoimmune and demyelinating disorder of the central nervous system with debilitating sensory and motor complications. There is still no definite cure for it and the main focus for its treatment mostly pivots around subsiding its severity and recurrence. Experimental autoimmune encephalomyelitis (EAE) is an established animal model of MS. S-allyl cysteine (SAC) is the active and main constituent of aged garlic extract with anti-inflammatory and neuroprotective property. This study was conducted to evaluate its possible protective effect in EAE model of MS. SAC was administered p.o. at a dose of 50 mg/kg/day to female C57BL/6 mice immunized with myelin oligodendrocytic glycoprotein (MOG35-55). Results showed that SAC is capable to alleviate clinical signs and severity of the disease and improved lumbar spinal cord tissue level of tumor necrosis factor α (TNFa), interleukin 17 (IL-17), activity-dependent neuroprotector homeobox (ADNP), microtubule-associated proteins 1A/1 B light chain 3A (MAP1LC3A), and matrix metalloproteinase 9 (MMP-9). In addition, SAC attenuated inflammatory cell infiltration, axonal demyelination, and axonal loss in lumbar spinal cord in EAE group, as demonstrated by H & E, Luxol fast blue (LFB), and Bielschowsky silver staining, respectively. Taken together, SAC could mitigate severity of MOG35-55-induced EAE as a valid model of MS via amelioration of pathogenic molecular mechanisms responsible for neuroinflammation and axonal damage.
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Antiinflamatorios/uso terapéutico , Cisteína/análogos & derivados , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/patología , Animales , Antiinflamatorios/farmacología , Cisteína/farmacología , Cisteína/uso terapéutico , Encefalomielitis Autoinmune Experimental/metabolismo , Femenino , Mediadores de Inflamación/antagonistas & inhibidores , Ratones , Ratones Endogámicos C57BL , Glicoproteína Mielina-Oligodendrócito/toxicidadRESUMEN
CONTEXT: Anxiety and depression are common in Alzheimer's disease (AD). Despite some evidence, it is difficult to confirm Lavandula officinalis Chaix ex Vill (Lamiaceae) as an anxiolytic and antidepressant drug. OBJECTIVE: The effects of L. officinalis extract were studied in scopolamine-induced memory impairment, anxiety and depression-like behaviour. MATERIALS AND METHODS: Male NMRI rats were divided into control, scopolamine alone-treated group received scopolamine (0.1 mg/kg) intraperitoneally (i.p.), daily and 30 min prior to performing behavioural testing on test day, for 12 continuous days and extract pretreated groups received aerial parts hydro alcoholic extract (i.p.) (100, 200 and 400 mg/kg), 30 min before each scopolamine injection. Memory impairment was assessed by Y-maze task, while, elevated plus maze and forced swimming test were used to measure anxiolytic and antidepressive-like activity. RESULTS: Spontaneous alternation percentage in Y maze is reduced by scopolamine (36.42 ± 2.60) (p ≤ 0.001), whereas lavender (200 and 400 mg/kg) enhanced it (83.12 ± 5.20 and 95 ± 11.08, respectively) (p ≤ 0.05). Also, lavender pretreatment in 200 and 400 mg/kg enhanced time spent on the open arms (15.4 ± 3.37 and 32.1 ± 3.46, respectively) (p ≤ 0.001). On the contrary, while immobility time was enhanced by scopolamine (296 ± 4.70), 100, 200 and 400 mg/kg lavender reduced it (193.88 ± 22.42, 73.3 ± 8.25 and 35.2 ± 4.22, respectively) in a dose-dependent manner (p ≤ 0.001). DISCUSSION AND CONCLUSION: Lavender extracts improved scopolamine-induced memory impairment and also reduced anxiety and depression-like behaviour in a dose-dependent manner.
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Ansiolíticos/farmacología , Antidepresivos/farmacología , Ansiedad/prevención & control , Conducta Animal/efectos de los fármacos , Depresión/prevención & control , Lavandula/química , Trastornos de la Memoria/prevención & control , Componentes Aéreos de las Plantas/química , Extractos Vegetales/farmacología , Escopolamina , Animales , Ansiolíticos/aislamiento & purificación , Antidepresivos/aislamiento & purificación , Ansiedad/inducido químicamente , Ansiedad/psicología , Cromatografía Líquida de Alta Presión , Depresión/inducido químicamente , Depresión/psicología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Etanol/química , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/psicología , Actividad Motora/efectos de los fármacos , Fenoles/aislamiento & purificación , Fenoles/farmacología , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Ratas , Solventes/química , Natación , Factores de TiempoRESUMEN
Status epilepticus (SE) is a life-threatening neurologic condition, instigating epileptogenesis to transform normal brain to an epileptic condition. SE is followed by spontaneous recurrent seizures (SRS) and final development of temporal lobe epilepsy (TLE) that is resistant to treatment. Neuroprotective strategies are increasingly put forward as a promising therapy to prevent and/or manage epileptic conditions. In this study, we investigated whether berberis alkaloid, i.e. berberine (BBR), could ameliorate intrahippocampal kainate-induced SE and its consequent epileptogenic process and to explore some underlying mechanisms. BBR was daily administered at doses of 25 or 50mg/kg. Results showed that BBR treatment of kainate-microinjected rats at a dose of 50mg/kg lowered the incidence of SE and SRS. It also significantly restored hippocampal level of reactive oxygen species (ROS), glutathione (GSH), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), activity of catalase and caspase 3, nuclear factor-
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Berberina/uso terapéutico , Hipocampo/metabolismo , Ácido Kaínico/toxicidad , Fármacos Neuroprotectores/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Estado Epiléptico/metabolismo , Animales , Berberina/farmacología , Relación Dosis-Respuesta a Droga , Hipocampo/efectos de los fármacos , Masculino , Fármacos Neuroprotectores/farmacología , Distribución Aleatoria , Ratas , Ratas Wistar , Estado Epiléptico/inducido químicamente , Estado Epiléptico/tratamiento farmacológicoRESUMEN
Neuroinflammation is known as a risk factor for cognitive deficit and dementia and its incidence increases with aging. S-allyl cysteine (SAC) is the active and main component of aged garlic extract with anti-inflammatory, neuroprotective, and nootropic potential. In this study, the protective effect of SAC against lipopolysaccharide (LPS)-induced cognitive deficit in the rat was investigated. For induction of learning and memory impairment and neuroinflammation, LPS was intraperitoneally injected at a dose of 167µg/kg for 7 days and SAC was administered p.o. at doses of 25, 50, or 100mg/kg/day, 30min after LPS, for seven days. Treatment of LPS-injected rats with SAC at a dose of 100mg/kg improved spatial recognition memory in Y maze, discrimination ratio in novel object discrimination task, and retention and recall in passive avoidance test. In addition, SAC at the latter dose mitigated lipid peroxidation marker malondialdehyde (MDA) and augmented key antioxidant defensive elements including superoxide dismutase (SOD), catalase and glutathione (GSH) in hippocampal homogenate and lowered acetylcholinesterase activity. Meanwhile, SAC down-regulated hippocampal nuclear factor-
Asunto(s)
Trastornos del Conocimiento/inducido químicamente , Trastornos del Conocimiento/prevención & control , Cisteína/análogos & derivados , Ajo/química , Lipopolisacáridos/farmacología , Acetilcolinesterasa/metabolismo , Animales , Reacción de Prevención/efectos de los fármacos , Biomarcadores/metabolismo , Proteínas de Unión al Calcio/metabolismo , Trastornos del Conocimiento/metabolismo , Trastornos del Conocimiento/fisiopatología , Cisteína/farmacología , Cisteína/uso terapéutico , Discriminación en Psicología/efectos de los fármacos , Proteína Ácida Fibrilar de la Glía/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatología , Interleucina-1beta/metabolismo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Proteínas de Microfilamentos/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Conducta Espacial/efectos de los fármacos , Conducta Espacial/fisiología , Receptor Toll-Like 4/metabolismoRESUMEN
Diabetic patients are at increased risk to develop cognitive deficit and senile dementia. This study was planned to assess the benefits of chronic carnosine administration on prevention of learning and memory deterioration in streptozotocin (STZ)-diabetic rats and to explore some of the involved mechanisms. Rats were divided into 5 groups: i.e., control, carnosine100-treated control, diabetic, and carnosine-treated diabetics (50 and 100mg/kg). Carnosine was injected i.p. at doses of 50 or 100mg/kg for 7 weeks, started 1 week after induction of diabetes using streptozotocin. Treatment of diabetic rats with carnosine at a dose of 100mg/kg at the end of the study lowered serum glucose, improved spatial recognition memory in Y maze, improved retention and recall in elevated plus maze, and prevented reduction of step-through latency in passive avoidance task. Furthermore, carnosine at a dose of 100mg/kg reduced hippocampal acetylcholinesterase (AChE) activity, lowered lipid peroxidation, and improved superoxide dismutase (SOD) activity and non-enzymatic antioxidant defense element glutathione (GSH), but not activity of catalase. Meanwhile, hippocampal level of nuclear factor-kappaB (NF-κB), tumor necrosis factor α (TNF-α), and glial fibrillary acidic protein (GFAP) decreased and level of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) increased upon treatment of diabetic group with carnosine at a dose of 100mg/kg. Taken together, chronic carnosine treatment could ameliorate learning and memory disturbances in STZ-diabetic rats through intonation of NF-κB/Nrf2/HO-1 signaling cascade, attenuation of astrogliosis, possible improvement of cholinergic function, and amelioration of oxidative stress and neuroinflammation.