RESUMEN
The normal inflammatory reaction protects the body from harmful external factors, whereas abnormal chronic inflammation can cause various diseases, including cancer. The purpose of the present study was to investigate the antiinflammatory activity of a mixture of Chrysanthemum zawadskii, peppermint and Glycyrrhiza glabra (CPG) by analyzing the expression levels of inflammatory mediators, cytokines and transcription factors in lipopolysaccharide (LPS)stimulated Raw264.7 cells. A nitric oxide assay, ELISA, western blotting and immunofluorescence staining were performed to investigate the antiinflammatory activity of the CPG mixture. Pretreatment of Raw264.7 cells with CPG inhibited the increase of inflammatory mediators (inducible nitric oxide synthase, cyclooxygenase2 and IFNß) induced by LPS. Additionally, it inhibited the production of proinflammatory cytokines (TNFα, IL6 and IL1ß). CPG suppressed LPSinduced phosphorylation of STAT1, AKT, Iκb and NFκB. Furthermore, CPG inhibited the translocation of NFκB into the nucleus. In summary, CPG could inhibit LPSinduced inflammation, which occurs primarily through the AKT/Iκb/NFκB signaling pathway in RAW264.7 cells.
Asunto(s)
Antiinflamatorios/farmacología , Chrysanthemum/química , Depuradores de Radicales Libres/farmacología , Glycyrrhiza/química , Macrófagos/efectos de los fármacos , Mentha piperita/química , Extractos Vegetales/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Hemo-Oxigenasa 1/metabolismo , Inflamación/inducido químicamente , Inflamación/metabolismo , Lipopolisacáridos/toxicidad , Macrófagos/citología , Macrófagos/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células RAW 264.7 , Factor de Transcripción STAT1/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Sophora flavescens, also known as Kushen, has traditionally been used as a herbal medicine. In the present study we evaluated the ameliorative effects of kushenol C (KC) from S. flavescens against tBHP (tert-Butyl hydroperoxide)-induced oxidative stress in hepatocellular carcinoma (HEPG2) cells and acetaminophen (APAP)-induced hepatotoxicity in mice. KC pretreatment protected the HEPG2 cells against oxidative stress by reducing cell death, apoptosis and reactive oxygen species (ROS) generation. KC pretreatment also upregulated pro-caspase 3 and GSH (glutathione) as well as expression of 8-Oxoguanine DNA Glycosylase (OGG1) in the HEPG2 cells. The mechanism of action was partly related by KC's activation of Akt (Protein kinase B (PKB)) and Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) in the HepG2 cells. In in vivo investigations, coadministration of mice with KC and APAP significantly attenuated APAP-induced hepatotoxicity and liver damage, as the serum enzymatic activity of aspartate aminotransferase and alanine aminotransferase, as well as liver lipid peroxidation and cleaved caspase 3 expression, were reduced in APAP-treated mice. Coadministration with KC also up-regulated antioxidant enzyme expression and prevented the production of proinflammatory mediators in APAP-treated mice. Taken together, these results showed that KC treatment has potential as a therapeutic agent against liver injury through the suppression of oxidative stress.