Protective Efefcts Of Centella Asiatica Extract On Lipopolysacchairde-induced Acute Lung Injury In Mice

Acute lung injury (ALI) is a serious clinical illness, which is the reflect ofsystemic inflammatory response syndrome mainly on the lungs. Although manyresearches on the mechanism and therapy of ALI are in progress, there are still noeffective measures and specific medicines to treat it. The feature of ALI includesinflammatory cells infiltration, alveolar edema, diffuse alveolar damage andhyaline membranes etc. ALI and its severe form, acute respiratory distress syndrome(ARDS), can lead to severe hypoxemia, pulmonary edema, and neutrophilaccumulation in the lung that impairs gas exchange, causes arterial hypoxemia andrespiratory failure. Although various strategies for suppressing the inflammatoryresponse have been tested in clinical trials, the morbidity and mortality are still veryhigh. ALI remains a severe disease and still presents a high mortality rate ofapproximately40%~60%. Lipopolysaccharide (LPS), a main component of outermembrane of Gram-negative bacteria, has been referred to be an important risk factorof induced ALI which is associated with the activation of numerous inflammatorycells. LPS can bind to the cell membrane receptor of the monocytes/macrophages andendothelial cells, then activate the signal-transduction system, thus resulting in thesynthesis and release of cytokines and inflammatory mediators, and it could lead tosystemic inflammatory response ranging from shock, sepsis to multiple organdysfunction etc.Centella Asiatsca is a traditional Chinese herbal medicine, has been known toexhibit antibacterial, anti-inflammatory and other important therapeutic activities. Inthis study, we aimed to investigate the protective effects and potential mechanisms ofCentella Asiatica extract action on inflammatory responses in lipopolysaccharide(LPS)-stimulated Raw264.7cells and an LPS-induced lung injury model. Methods：We investigated the efficacy of Centella Asiatica extract on cytokinelevels induced by LPS in bronchoalveolar lavage fluid (BALF) and RAW264.7cells.The production of cytokine (TNF-α and IL-6) was measured by enzyme-linkedimunosorbent assay (ELISA). The lung wet-to-dry weight ratios and were measuredin LPS-challenged mice, and lung histopathologic changes observed via paraffinsection were assessed. To further study the mechanism of Centella Asiatica extractprotective effects on ALI, the activation of NF-κB p65subunit and the degradation ofIκBα were tested by western blot assay.Result: We found that Centella Asiatica extract treatment at20,40or80mg/kgdose-dependently attenuated LPS-induced pulmonary inflammation by reducinginflammatory infiltration, histopathological changes, descended cytokine production,and pulmonary edema initiated by LPS. Furthermore, our results suggested thatCentella Asiatica extract suppressed inflammatory responses in LPS-induced ALIthrough inhibition of the phosphorylation of NF-κB p65subunit and the degradationof its inhibitor IκBα.Conelusion: In summary, our study demonstrated that CentellaAsiatica extract exerted anti-inflammatory effects in viro and in vivo.Meantime, Centella Asiatica extract shows a protective effect against LPS-inducedALI and might be a new preventive agent of ALI in the clinical setting.