Genipin alleviates LPS-induced acute lung injury by inhibiting NF-κB and NLRP3 signaling pathways.

Genipin has been reported to have anti-inflammatory effect. However, its role on lipopolysaccharide (LPS)-induced acute lung injury (ALI) has not been explored. This study aimed to evaluate the effect of genipin on murine model of acute lung injury induced by LPS. The mice were treated with genipin 1h before LPS administration. 12h later, the myeloperoxidase (MPO) in lung tissues and lung wet/dry ratio were detected. The levels of TNF-α, IL-1β and IL-6 in bronchoalveolar lavage fluid (BALF) were measured by ELISA. Apart from this, we use western blot to detect the protein expression in the NF-κB and NLRP3 signaling pathways. The results showed that the treatment of genipin markedly attenuated the lung wet/dry ratio and the MPO activity. Moreover, it also inhibited the levels of TNF-α, IL-1β, IL-6 in the BALF. In addition, genipin significantly inhibited LPS-induced NF-κB and NLRP3 activation. In conclusion, these results demonstrate that genipin protected against LPS-induced ALI through inhibiting NF-κB and NLRP3 signaling pathways.

Zhang A ，Wang S ，Zhang J ，Wu H ... -  《-》

Therapeutic effect of methyl salicylate 2-O-β-d-lactoside on LPS-induced acute lung injury by inhibiting TAK1/NF-kappaB phosphorylation and NLRP3 expression.

Acute lung injury (ALI), characterized by pulmonary edema and inflammatory cell infiltration, is a common syndrome of acute hypoxemic respiratory failure. Methyl salicylate 2-O-β-d-lactoside (MSL), a natural derivative of salicylate extracted from Gaultheria yunnanensis (Franch.) Rehder, was reported to have potent anti-inflammatory effects on the progression of collagen or adjuvant-induced arthritis in vivo and in vitro. The aim of this study is to investigate the therapeutic effect of MSL on lipopolysaccharide (LPS)-induced acute lung injury and reveal underlying molecular mechanisms. Our results showed that MSL significantly ameliorated pulmonary edema and histological severities, and inhibited IL-6 and IL-1β production in LPS-induced ALI mice. MSL also reduced MPO activity in lung tissues and the number of inflammatory cells in BALF. Moreover, we found that MSL significantly inhibited LPS-induced TAK1 and NF-κB p65 phosphorylation, as well as the expression of NLRP3 protein in lung tissues. Furthermore, MSL significantly inhibited LPS-induced TAK1 and NF-κB p65 phosphorylation in Raw264.7 cells. In addition, MSL significantly inhibited nuclear translocation of NF-κB p65 in cells treated with LPS in vitro. Taken together, our results suggested that MSL exhibited a therapeutic effect on LPS-induced ALI by inhibiting TAK1/NF-κB phosphorylation and NLRP3 expression.

Yang S ，Yu Z ，Yuan T ，Wang L ，Wang X ，Yang H ，Sun L ，Wang Y ，Du G ... -  《-》

Fraxin ameliorates lipopolysaccharide-induced acute lung injury in mice by inhibiting the NF-κB and NLRP3 signalling pathways.

Fraxin, the effective component of the Chinese traditional medicine Cortex Fraxini, is reported to have anti-inflammatory effects. This study assessed the anti-inflammatory effect of fraxin on the lipopolysaccharide (LPS)-induced inflammatory response in A549 cells and the protective efficacy on LPS-induced acute lung injury (ALI) in mice. Fraxin reduced LPS-induced TNF-α, IL-6 and IL-1β production in A549 cells and alleviated the LPS-induced wet/dry (W/D) weight ratio and the effects observed via histopathological examination of the lung in vivo. Furthermore, fraxin reduced the protein concentrations in the broncho-alveolar lavage (BAL) fluid and cytokine production in the sera. Fraxin also clearly attenuated the oxidation index, including the activity of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH). Immunohistochemistry analysis showed that fraxin suppressed LPS-induced inflammatory damage. The expression of proteins involved in the NF-κB and NLRP3 inflammatory corpuscle signalling pathways was consistent between the lung tissues and cell samples. Overall, fraxin played a protective role in LPS-induced lung injury by inhibiting the NF-κB and NLRP3 signalling pathways.

Li W ，Li W ，Zang L ，Liu F ，Yao Q ，Zhao J ，Zhi W ，Niu X ... -  《-》

CORM-2 inhibits TXNIP/NLRP3 inflammasome pathway in LPS-induced acute lung injury.

Jiang L ，Fei D ，Gong R ，Yang W ，Yu W ，Pan S ，Zhao M ，Zhao M ... -  《-》

Casticin inhibits lipopolysaccharide-induced acute lung injury in mice.

Casticin, an active compound isolated from Vitex Fructus, has been reported to have anti-inflammatory effects in previous studies. The present study was designed to evaluate the protective effects of casticin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and clarify the underlying mechanisms. ALI was induced by intratracheal instillation of LPS. Casticin was administrated 1h before or after LPS challenge. The results showed that casticin decreased LPS-induced lung histopathological changes, MPO activity, and lung wet/dry weight ratio. Casticin also inhibited the numbers of inflammatory cells and the levels of inflammatory cytokines TNF-α, IL-6, and IL-1β production. Furthermore, casticin suppressed LPS-induced NF-κB activation, and NLRP3, ASC, and caspase-1 expression. In conclusion, the results suggested that casticin had a protective effect against LPS-induced ALI. Casticin protected against LPS-induced ALI by inhibiting inflammatory cytokines production through the inhibition of NF-κB and NLRP3 signaling pathways.

Wang C ，Zeng L ，Zhang T ，Liu J ，Wang W ... -  《-》