Acute lung injury induced by lipopolysaccharide is inhibited by wogonin in mice via reduction of Akt phosphorylation and RhoA activation

作者:Yeh Yen Cheng; Yang Ching Ping; Lee Shiuan Shinn; Horng Chi Ting; Chen Hung Yi; Cho Ta Hsiung; Yang Ming Ling; Lee Chien Ying; Li Miao Cing; Kuan Yu Hsiang
来源:Journal of Pharmacy and Pharmacology, 2016, 68(2): 257-263.
DOI:10.1111/jphp.12500

摘要

ObjectivesNeutrophil infiltration into the lung is the critical characteristic of acute lung injury (ALI), which is a clinical state with acute inflammatory syndrome. Up to now, there is no effective medicine for ALI. Wogonin has been shown to posses serval biological activities including anti-inflammation, anti-oxidant and anti-carcinoma. MethodsAcute lung injury was induced by intratracheal injection of LPS, and wogonin at various concentrations was injected intraperitoneally 30 min prior to LPS. Contents of myeloperoxidase (MPO) and expression of chemokines and adhesion molecules were determined by commercially and ELISA assay kits, respectively. Akt phosphorylation and RhoA activation were measured by western blot and RhoA pull-down activation assay, respectively. Key findingNeutrophil infiltration was reduced by wogonin in a concentration-dependent manner in the LPS-induced ALI mice model. LPS-induced proinflammatory cytokines and adhesion molecules were inhibited by wogonin in bronchoalveolar lavage fluid (BALF) with LPS-induced ALI. Furthermore, wogonin suppressed Akt phosphorylation and RhoA activation in lungs in LPS-induced ALI. The similar parallel trend was observed as wogonin reduced LPS-induced neutrophils infiltration, proinflammatory cytokines generation, adhesion molecules expression, Akt phosphorylation, and RhoA activation. SummaryThese results suggested that the effects of wogonin in LPS-induced ALI were induced by inhibition of Akt phosphorylation and RhoA activation.