Protective Effects Of Total Flavonoids From Abutilon Theophrasti Medic.leaves On Acute Lung Injury In Mice

Acute lung injury?ALI?accompanies with the damages of epithelial and capillary endothelial cells,and the typical pathological changes are diffuse pulmonary interstitial,alveolar edema and hypoxic respiratory insufficiency symptom in clinic.At present,the death rate is about 50%in some severe cases.There are same therapeutic method for inflammation,including restraining inflammatory factors,improving oxygenation and correcting hypoxia.In recent years,the relevant research indicated that traditional Chinese medicine?TCM?exhibited a better and significant effect on alleviating and treating of ALI.Flavonoids are a kind of active ingredients in many kinds of TCMs,and display some good activities,such as reducing pressure,improving the microenvironment of blood vessels,antioxidation,antibacterial,anti-inflammation and other effects.Abutilon theophrasti Medic.,as an annual herb,is rich in flavonoidsand especially leaves.In this study,the anti-inflammatory effect of total flavonoids extract of Abutilon theophrasti Medic.leaves?TFE?was evaluated with the model of acute lung injury induced by LPS in mice.The content of PGE₂,TNF-?,IL-6,IL-10 and IL-1?in lung tissues of mice was detected by enzyme-associated immunosorbent assay?ELISA?method.Griess method was used to measure the content of NO in the lung tissue homogenate.For further evaluation of the effect of TFE on the secretion of inflammatory factors and mediators,the mRNA and proteins levels of nitric oxide synthase?iNOS?,cyclooxygenase 2?COX-2?,ERK1/2,p38?,p65,JNK and I?B were determinated by fluorescence quantitative PCR and western methods,respectively.The experimental results revealed that TFE significantly decreased the content of NO,PGE₂,TNF-?,IL-6 and IL-1?in the ALI mice induced by LPS,and increased the content of IL-10.In addition,the mRNA expressions of iNOS,COX-2,ERK1/2,p38,p65 and JNK were significantly reduced by TFE,and the expression of I?B was increased.TFE can also significantly inhibit the phosphorylation of ERK1/2,p38,p65 and JNK proteins,and significantly reduce the protein expression of COX-2.This study indicated that the TFE directly inhibited the inflammatory by reducing the amount of TNF-??IL-6 and IL-1?,and played an anti-inflammatory effect by reducing the content,mRNA and protein levels of iNOS,COX-2.The activation of the LPS-induced NF-?B signal transduction pathway can be inhibited by TFE via reducing the mRNA levels and protein phosphorylation levels of I?B and p65.At the same time,TFE can inhibit the activation of MAPK signal transduction pathway in ALI mice by decreasing the mRNA levels and protein phosphorylation levels of ERK1/2,JNK and p38.In brief,this research systematically evaluated the anti-inflammatory effects of TFE,and further revealed the anti-inflammation mechanisms through regulating the two signal transduction pathways of NF-?B and MAPKs and inhibiting the expression of inflammatory cytokines in ALI mice,which was providing a reference for the effective prevention and treatment of inflammation in veterinary clinic,and new ideas for the development of green veterinary drugs.