Therapeutic effects of rosmarinic acid on airway responses in a murine model of asthma.

Rosmarinic acid (RA) is an active component of a traditional Chinese herbal medicine. Previously, we reported that RA exerted a strong anti-inflammatory effect in a mouse acute lung injury model. Therefore, we hypothesized that RA might also have potential therapeutic effects in a murine model of asthma. In this study, we aimed to evaluate the anti-asthmatic activity of RA and explored its possible molecular mechanisms of action. Female BALB/c mice that had been sensitized to and challenged with ovalbumin (Ova) were treated with RA (20mg/kg) 1h after challenge. The results showed that RA greatly diminished the number of inflammatory cells and the production of Th2 cytokines in the bronchoalveolar lavage fluid (BALF); significantly reduced the secretion of total IgE, Ova-specific IgE, and eotaxin; and markedly ameliorated airway hyperresponsiveness (AHR) compared with Ova-induced mice. Histological studies further revealed that RA substantially decreased inflammatory cells infiltration and mucus hypersecretion compared with Ova-induced mice. Moreover, our results suggested that the protective effects of RA were mediated by the inhibition of JNK and p38 MAPK phosphorylation and nuclear factor-κB (NF-κB) activation. Furthermore, RA treatment resulted in a significant reduction in the mRNA expression of AMCase, CCL11, CCR3, Ym2 and E-selectin in lung tissue. These findings suggest that RA may effectively delay the development of airway inflammation and could thus be used as a therapy for allergic asthma.

Pretreatment with the compound asperuloside decreases acute lung injury via inhibiting MAPK and NF-κB signaling in a murine model.

Asperuloside, an iridoid glycoside found in Herba Paederiae, is a component from traditional Chinese herbal medicine. In this study, we aimed to investigate the protective effects and potential mechanisms of asperuloside action on inflammatory responses in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells and an LPS-induced lung injury model. The pro-inflammatory cytokines and signaling pathways were measured by enzyme-linked immunosorbent assays (ELISA) and Western blotting to determine the effects of asperuloside. We found that asperuloside can significantly downregulate tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, and IL-6 levels in vitro and in vivo, and treatment with asperuloside significantly reduced the lung wet-to-dry weight, histological alterations and myeloperoxidase activity in a murine model of LPS-induced acute lung injury (ALI). In addition, Western blot analysis that pretreatment with asperuloside remarkably blunted the phosphorylation of inhibitor of nuclear factor kappa-B (IκBα), extracellular signal-related kinases 1 and 2 (ERK1/2), c-Jun. N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) in LPS-stimulated inflammation. These results indicate that asperuloside exerts its anti-inflammatory effect in correlation with inhibition of a pro-inflammatory mediator through suppressing nuclear factor kappa-B (NF-κB) nuclear translocation and MAPK phosphorylation in a dose-dependent manner.

D(-)-Salicin inhibits the LPS-induced inflammation in RAW264.7 cells and mouse models.

D(-)-Salicin is a traditional medicine which has been known to exhibit anti-inflammation and other therapeutic activities. The present study aimed to investigate whether D(-)-Salicin inhibited the LPS-induced inflammation in vivo and in vitro. We evaluated the effect of D(-)-Salicin on cytokines (TNF-α, IL-1ß, IL-6 and IL-10) in vivo and in vitro by enzyme-linked immunosorbent assay and signaling pathways (MAPKs and NF-κB) in vivo by Western blot. The results showed that D(-)-Salicin markedly decreased TNF-α, IL-1ß and IL-6 concentrations and increased IL-10 concentration. In addition, western blot analysis indicated that D(-)-Salicin suppressed the activation of MAPKs and NF-κB signaling pathways stimulated by LPS. To examine whether D(-)-Salicin ameliorated LPS-induced lung inflammation, inhibitors of MAPKs and NF-κB signaling pathways were administrated intraperitoneally to mice. Interference with specific inhibitors revealed that D(-)-Salicin-mediated cytokine suppression was through MAPKs and NF-κB pathways. In the mouse model of acute lung injury, histopathologic examination indicted that D(-)-Salicin suppressed edema induced by LPS. So it is suggest that D(-)-Salicin might be a potential therapeutic agent against inflammatory diseases.

Asiaticoside attenuates lipopolysaccharide-induced acute lung injury via down-regulation of NF-κB signaling pathway.

Asiaticoside (AS), a triterpene glycoside isolated from Centella asiatica, has been shown to possess potent anti-inflammatory activity. However, the detailed molecular mechanisms of AS on lipopolysaccharide (LPS)-induced acute lung injury (ALI) model in mice are scanty. The purpose of this study was to evaluate the effect of AS on LPS-induced mouse ALI via down-regulation of NF-κB signaling pathway. We investigated the efficacy of AS on cytokine levels induced by LPS in bronchoalveolar lavage fluid (BALF) and RAW 264.7 cells. The production of cytokine (TNF-α and IL-6) was measured by enzyme-linked immunosorbent assay (ELISA). The lung wet-to-dry weight ratios were measured in LPS-challenged mice, and lung histopathologic changes observed via paraffin section were assessed. To further study the mechanism of AS protective effects on ALI, the activation of NF-κB p65 subunit and the degradation of IκBα were tested by western blot assay. We found that AS treatment at 15, 30 or 45mg/kg dose-dependently attenuated LPS-induced pulmonary inflammation by reducing inflammatory infiltration, histopathological changes, descended cytokine production, and pulmonary edema initiated by LPS. Furthermore, our results suggested that AS suppressed inflammatory responses in LPS-induced ALI through inhibition of the phosphorylation of NF-κB p65 subunit and the degradation of its inhibitor IκBα, and might be a new preventive agent of ALI in the clinical setting.