RESUMEN
Isoalantolactone (ISO), a sesquiterpene lactone isolated from Inula helenium, is known to have anti-inflammatory activity. Here, using a mouse model of acute lung injury, we investigated the effects of ISO on lung inflammation in vivo. ISO (2.5, 5, 10â¯mg/kg) was administered 1â¯h before LPS treatment. Histopathological changes suggested that ISO attenuated the injury of lung tissues induced by LPS. ISO also inhibited LPS-induced MPO activity, MDA content, lung W/D ratio, and the production of inflammatory cytokines TNF-α and IL-1ß. LPS decreased the activities of the antioxidant enzymes SOD, GPX, and CAT and the decreases were inhibited by ISO. Further studies were performed to detect the Nrf2 and NF-κB signaling pathway. The results showed that ISO significantly suppressed LPS-induced NF-κB activation, as well as PI3K and AKT phosphorylation. Additionally, the expression of Nrf2 and HO-1 were dose-dependently up-regulated by the treatment of ISO. Taken together, the results indicate the protective action of ISO against LPS-induced ALI were through activation of the Nrf2 signaling pathway.
Asunto(s)
Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/prevención & control , Lipopolisacáridos/efectos adversos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Sesquiterpenos/farmacología , Lesión Pulmonar Aguda/patología , Animales , Antiinflamatorios/farmacología , Antioxidantes/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Interleucina-1beta/metabolismo , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Sustancias Protectoras , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Baicalin is a naturally occurring compound with anticancer, antioxidant, and anti-inflammatory properties. However, the mechanism underlying its anticancer activity on nonsmall cell lung cancer (NSCLC) remains unclear. METHODS: The effects of baicalin on the progression and metastasis of experimental NSCLC cell lines were studied in vitro and in vivo. Wound-healing and transwell assays were performed to evaluate the potency of baicalin and the motility and migration ability of NCI-H460 cells. Immunofluorescence assay, western blot assay, and immunohistochemistry test were conducted to investigate the inhibiting effect of baicalin on the epithelial-mesenchymal transition (EMT) of NSCLC. RESULTS: Baicalin inhibited the proliferation and migration of NCI-H446 human NSCLC cells in a dose-dependent manner, reduced the expression levels of phospho-3-phosphoinositide-dependent protein kinase 1 (p-PDK1) and phosphor-serine/threonine-protein kinase (p-AKT), reversed the levels of EMT markers, and inhibited the migration of NSCLC cells. CONCLUSIONS: Baicalin impedes EMT by inhibiting the PDK1/AKT pathway in human NSCLC and thus may be an effective alternative treatment for carcinoma and a new candidate antimetastasis drug.