RESUMEN
Lindera obtusiloba is widespread in northeast Asia and used for treatment of improvement of blood circulation and anti-inflammation. In this study, we investigated anti-inflammatory and anti-oxidant effects of the methanolic extract of L. obtusiloba leaves (LOL) in an ovalbumin (OVA)-challenged allergic asthma model and tumor necrosis factor (TNF)-α-stimulated NCI-H292 cell. Female BALB/c mice were sensitized with OVA by intraperitoneal injection on days 0 and 14, and airway-challenged with OVA from days 21 to 23. Mice were administered 50 and 100 mg/kg of LOL by oral gavage 1 h before the challenge. LOL treatment effectively decreased airway hyper-responsiveness and inhibited inflammatory cell recruitment, Th2 cytokines, mucin 5AC (MUC5AC) in bronchoalveolar lavage fluid in OVA-challenged mice, which were accompanied by marked suppression of airway inflammation and mucus production in the lung tissue. LOL pretreatment inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) with suppression of activator protein (AP)-1 and MUC5AC in the lung tissue. LOL also down-regulated expression of inflammatory cytokines, and inhibited the activation of NF-κB in TNF-α-stimulated NCI-H292 cells. LOL elevated the translocation of nuclear factor-erythroid 2-related factor (Nrf-2) into nucleus concurrent with increase of heme oxyngenase-1 (HO-1) and NAD(P)H quinine oxidoreductase 1 (NQO1). Moreover, LOL treatment exhibited a marked increase in the anti-oxidant enzymes activities, whereas effectively suppressed the production of reactive oxygen species and nitric oxide, as well as lipid peroxidation in lung tissue of OVA-challenged mice and TNF-α-stimulated NCI-H292 cells. These findings suggest that LOL might serve as a therapeutic agent for the treatment of allergic asthma.
RESUMEN
Spiraea prunifolia var. simpliciflora (SP) is traditionally used as an herbal remedy to treat fever, malaria, and emesis. This study aimed to evaluate the anti-oxidative and anti-inflammatory properties of the methanol extract of SP leaves in tumor necrosis factor (TNF)-α-stimulated NCI-H292 cells and in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. SP decreased the number of inflammatory cells and the levels of TNF-α, interleukin (IL)-1ß, and IL-6 in the bronchoalveolar lavage fluid, and inflammatory cell infiltration in the lung tissues of SP-treated mice. In addition, SP significantly suppressed the mRNA and protein levels of TNF-α, IL-1ß, and IL-6 in TNF-α-stimulated NCI-H292 cells. SP significantly suppressed the phosphorylation of the mitogen-activated protein kinases (MAPKs) and p65-nuclear factor-kappa B (NF-κB) in LPS-induced ALI mice and TNF-α-stimulated NCI-H292 cells. SP treatment enhanced the nuclear translocation of nuclear factor erythroid 2-related factor (Nrf2) with upregulated antioxidant enzymes and suppressed reactive oxygen species (ROS)-mediated oxidative stress in the lung tissues of LPS-induced ALI model and TNF-α-stimulated NCI-H292 cells. Collectively, SP effectively inhibited airway inflammation and ROS-mediated oxidative stress, which was closely related to its ability to induce activation of Nrf2 and inhibit the phosphorylation of MAPKs and NF-κB. These findings suggest that SP has therapeutic potential for the treatment of ALI.