RESUMO
Acute kidney injury (AKI) is a major clinical problem associated with high morbidity and mortality. Esculentoside A (EsA), a kind of saponin isolated from the root of the Chinese herb Phytolaca esculenta, has been reported to have anti-inflammatory effect. In this study, we aimed to investigate the protective effects of EsA on LPS-induced AKI in mice. The protective effects of EsA was evaluated by detecting kidney histological change, blood urea nitrogen (BUN) and creatinine levels, and inflammatory cytokines production. The results showed that EsA significantly attenuated LPS-induced kidney histological change, as well as BUN and creatinine levels. EsA also inhibited LPS-induced TNF-α, IL-1ß, and IL-6 production. LPS-induced NF-κB activation was significantly suppressed by treatment of EsA. In addition, EsA up-regulated the expression of PPAR-γ in a dose-dependent manner. In conclusion, EsA protected mice effectively from LPS-induced AKI by PPAR-γ, which subsequently inhibited LPS-induced inflammatory response.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Lipopolissacarídeos/efeitos adversos , Ácido Oleanólico/análogos & derivados , PPAR gama/metabolismo , Saponinas/antagonistas & inibidores , Injúria Renal Aguda/patologia , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Ácido Oleanólico/administração & dosagem , Ácido Oleanólico/antagonistas & inibidores , Saponinas/administração & dosagem , Fator de Necrose Tumoral alfa/metabolismoRESUMO
In the paper, we observed the effect of ellagic acid (EA) on myocardial morphology and cardiac function and explored the mechanism of miR-140-3p-mediated EA in ventricular remodeling. The experimental animals were divided into 3 groups: control group, AMI group, AMI+EA group. Intragastric administration for 4 weeks was initiated on the first day after surgery in rats. Rodent echocardiography was used to measure heart size and cardiac function. The level of fibrosis was observed by Masson staining. The number of cell apoptosis was detected by TUNEL method. The expression of miR-140-3p and MKK6 was measured by qRT-PCR and Western blot, respectively. The results showed that EA could effectively improve the left ventricular function of AMI rats, reduce fibrosis area and infarct area. Moreover, EA significantly increased the expression of miR-140-3p and inhibited the expression of MKK6. However, miR-140-3p inhibitor up-regulated MKK6 expression, and miR-140-3p overexpression reversed the expression. In addition, EA could inhibit cell apoptosis, while miR-140-3p inhibitor increased cell apoptosis. After transfection with si-MKK6, the level of cell apoptosis was significantly decreased. These results indicated that EA improved ventricular remodeling after myocardial infarction by up-regulating miR-140-3p expression and inhibiting MKK6 expression.
Assuntos
Ácido Elágico/uso terapêutico , MicroRNAs/genética , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/fisiopatologia , Regulação para Cima , Remodelação Ventricular , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Sequência de Bases , Ácido Elágico/farmacologia , MAP Quinase Quinase 6/metabolismo , Masculino , MicroRNAs/metabolismo , Infarto do Miocárdio/genética , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Remodelação Ventricular/efeitos dos fármacosRESUMO
Angelicin, a furocoumarin found in Psoralea corylifolia L. fruit, has been reported to have anti-inflammatory activity. The purpose of this study was to determine the protective effects of angelicin on allergic asthma induced by ovalbumin (OVA) in mice. Mice were sensitized to OVA (on days 0 and 14) and challenged with OVA three times (on days 21 to 23). Angelicin (2.5, 5, 10 mg/kg) was given intraperitoneally 1 h before OVA treatment after the initial OVA sensitization. The production of IL-4, IL-5, and IL-13 in BALF and IgE in the serum were measured by ELISA. Lung histological changes were detected by using hematoxylin and eosin (H&E) stain. The results showed that angelicin significantly inhibited inflammatory cells infiltration into the lungs. Histological studies showed that angelicin significantly attenuated OVA-induced lung injury. Meanwhile, treatment of angelicin dose-dependently inhibited OVA-induced the production of IL-4, IL-5, and IL-13 in BALF and IgE in the serum. Furthermore, angelicin was found to inhibit airway hyperresponsiveness and NF-kB activation. In conclusion, our results suggested that angelicin inhibited allergic airway inflammation and hyperresponsiveness by inhibiting NF-kB activation.