ABSTRACT
Objective To investigate the potential therapeutic effect of luteolin on sepsis-induced ALI and the underlying mechanisms.Methods Total of 50 mice were randomly(random number) divided into five groups:a sham control group,a sepsis-induced ALI group,and three sepsis groups pre-treated with 20,40,and 80 mg/kg body weight luteolin.Mice in the treatment groups were pre-treated with luteolin at the respective oral dose two days before ALI induction.The lungs were isolated for histopathological examinations,and the bronchoalveolar lavage fluid (BALF) was collected for biochemical analyses.Results Luteolin significantly attenuated sepsis-induced ALI.Additionally,luteolin treatment decreased protein and inflammatory cytokine concentration and the number of infiltrated inflammatory cells in BALF compared with that in the non-treated sepsis mice.Pulmonary myeloperoxidase (MPO) activity was lower in the luteolin-pre-treated sepsis groups than in the sepsis group.The mechanism underlying the protective effect of luteolin on sepsis is related to the up-regulation of certain antioxidation genes,including inducible nitric oxide synthase (iNOS),cyclooxygenase-2 (COX-2),superoxide dismutases (SODs),and heme oxygenase 1 (HO-1),and the reduction of inflammatory responses through blockage of the activation of the nuclear factor (NF)-κB pathway.Conclusions Luteolin pre-treatment inhibits sepsis-induced ALI through its anti-inflammatory and antioxidative activity,suggesting that luteolin may be a potential therapeutic agent for sepsis-induced ALI.
ABSTRACT
Objective To study the effect of artesunate on inflammatory responses to severe pneumonia by regulating macrophage migration inhibitory factor (MIF) in rats.Methods Total of 100 SD by random (random number) assigned,20 rats were control group,80 SD rats with severe pneumonia were caused by Klebsiella pneumoniae,60 SD rats were treated with different concentrations (20,40,80 mk/kg) of artesunate after modeling.The pathological changes of lung tissue,the level of MIF myeloperoxidase activity and inflammatory cell infiltration in lung tissue of rats were evaluated.Results After treatment with artesunate,the severity of inflammation was significantly alleviated in rats with severe pneumonia evidenced by decrease in myeloperoxidase activity [severe pneumonia:(17.5 ± 1.5) vs.treatment group:(7.5 ±2.0)] and reduction in inflammatory cell infiltration (severe pneumonia:27 × 106 vs.treatment group:12.5 × 106).Similarly,the artesunate also reduced the production of inflammatory cytokines significantly in bronchoalveolar lavage fluid (IL-1 in severe pneumonia group:(1 100 ± 50) pg/ml vs.treatment group:(400 ± 60) pg/ml;IL-6 in severe pneumonia group:(700-± 30) pg/ml vs.treatment group:(200 ±40) pg/ml;IL-10 in severe pneumonia group:(500 ± 70) pg/ml vs.treatment group:(200 ± 40) pg/ml;TNF-αin severe pneumonia group:(500 ± 80) pg/ml vs.treatment group:(150 ± 50) pg/ml.In addition,artesunate inhibited the level and production of MIF,thus inhibiting the inflammatory responses mediated by MIF.Conclusions Artesunate had a protective effect on pneumonia caused by Klebsiella pneumoniae in rats via inhibiting the inflammation responses mediated by MIF.This study provided a molecular basis for newly developed drugs applied to the treatment of pneumonia caused by Klebsiella pneumoniae in rats.