| Acute lung injury (ALI) is a complex syndrome of intense pulmonaryinflammatory response and could be associated with many factors. Despite recentadvances in medical condition, ALI is a primary cause of death of intensive carepatients and its mortality rate is about35%-40%. There is no effective treatment yet foracute lung injury. Lipopolysaccharide (LPS) is a prominent cell wall component ofgram-negative bacteria, and the intratracheal instillation of LPS has been extensivelyused to study the pathogenesis of ALI. LPS can cause microvascular injury and diffusedalveolar damage with pulmonary hemorrhage, edema and neutrophil infiltration withoutcausing systemic inflammation and multi organ failure, so it is appropriate forestablishing the model of ALI. At present, steroid anti-inflammatory drug is usuallyused to treat ALI, but it can cause serious side effects. Licorice has expectorant anddemulcent properties, has been used traditionally in the treatment of coughs withoutserious adverse reactions. Licorice Flavonoids is the main component of licorice, and itsanti-inflammatory effects have been confirmed and applied. Therefore, we investigatedwhether Licorice Flavonoids has any protective effects on ALI.To evaluate the LPS-induced inflammation, interstitial edema, hemorrhage, andthickening of the alveolar wall, we established the mouse model of acute lung injury bynasal instillation of LPS. Mice were treated with licorice flavonoids respectively beforeand after LPS nasal instillation, histological lung sections were subjected to H&Estaining. The results showed that licorice flavonoids could significantly decreaseinflammatory infiltration in lung, and treatment effect of licorice flavonoids is betterthan prophylaxis effect.In addition, we also investigated production of cytokines at different times in bothprevention group and treatment group, such as TNF-α, IL-1β and IL-6. The resultsshowed that Licorice flavonoids could suppress TNF-α, IL-1β and IL-6expression levels.NF-κB is a nuclear transcription factor and could be activated by LPS, it can inducethe expression of inflammatory factors, when activated it can increase the production ofpro-inflammatory factors. To investigate the effects of licorice flavonoids on NF-κBpathway, Western blot analysis were applied to examine the expression of NF-κB. Theresults showed that licorice flavonoids could inhibit the activation of NF-κB and had abetter treatment than prevention.Similarly, NF-κB pathway plays an important role in the pathogenesis of septicshock, while it can regulate the release of various pro-inflammatory cytokines. Tofurther study on the protective effect of licorice flavonoids on inflammation, we alsobuilt up the experimental model of LPS-induced septic shock. Septic shock is anextreme inflammatory reaction can cause organ failure. It can be induced by a variety ofpathogenic microorganisms, and the proportion of infections due to gram-negativebacteria can reach30%-80%. Therefore, we investigated whether licorice flavonoidshave protective effect on septic shock by detecting the expression of pro-inflammatorycytokines. Results confirmed that licorice flavonoids may reduce the production ofTNF-α, IL-1β and IL-6.In conclusion, our results suggested that licorice flavonoids could effectivelydecrease inflammation in lung, suppressed the expression of pro-inflammatory factorsby inhibiting the activation of the transcription factor NF-κB. In addition, licoriceflavonoids also possess inhibitory effect on TNF-a, IL-1β and IL-6production inseptic shock. These results indicate that licorice flavonoids could attenuateinfammatory injury induced by LPS, and provides a theoretical basis for clinical use oflicorice flavonoids. |
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