The Protective Effects Of Apigenin On LPS-induced Acute Lung Injury In Mice

Acute lung injury(ALI) is an usually caused by trauma, infection, shock, and many other non cardiac causes an acute, progressive respiratory dysfunction.The main features of the disease is a stubborn hypoxemia, the breath frequency increases, heavy breathing, dysonea, X-ray analysis showed a diffuse infiltration of alveolar.Applying Chinese herbal medicine in treatment of ALI is characterized by a variety of Chinese herbal medicine and low cost, obvious effects of anti-inflammatory, improving immunity, etc. Apigenin, a kind of natural flavonoid compounds that existed in the dry parsley leaf umbrella plant, has low toxicity, effect remarkable advantages. Studies have shown that apigenin also has resistance mutation, anti-inflammatory, anti-viral, inducing-apoptosis and inhibition of cell cycle, anti-oxidative stress. However, the effects of apigenin on LPS-induced acute lung injury has not been reported. In this paper, the acute lung injury was established based on LPS-induced mice and RAW264.7 cell model to detect the effects of apigenin on the in vivo and in vitro model of acute lung injury, and to explore its possible mechanism.Acute lung injury was administrated intranasally by LPS. The acute lung injury in mice was evatluated by H.E dyeing, lung tissue for wet dry weight ratio(W/D), MPO activity and inflammatory cytokines in BALF. The results showed that damaged lung organization structure, a large amount of inflammatory cells infiltration and accompanied by thickening of alveolar walls were significantly induced by LPS. These results suggest that acute lung injury in mice were successfully established by LPS. Pretreatment of apigenin significantly decreased LPS-induced wet dry weight ratio, MPO activity and inflammatory cells infiltration in HE section. In addition, apigenin markedly reduced the levels of TNF-α, IL-1? and IL-6 in BALF. Furthermore, results of western blotting showed that apigenin significantly inhibit the phosphorylation of p65, p38, JNK and ERK in lung tissue.In order to investigate the effects of apigenin on acute lung injury in mice, RAW264.7 cells was used to study the anti-inflammatory effects of apigenin on acute lung injury and to further explore its possible mechanism.The toxic effect of apigenin on RAW264.7 cells was detected by MTT method, TNF-α, IL-1? and IL-6 in BALFwas detected by q RT-PCR, the phosphorylation of p65, p38, JNK and ERK were evaluated by western blotting. The results showed that apigenin has no cytotoxicity to RAW264.7. And apigenin significantly decrease the m RNA expressions of TNF-α, IL-1? and IL-6 and the phosphorylation of p65, p38, JNK and ERK.In conlusion, we found that apigenin protects LPS-induced acute lung injury may be through its anti-inflammatory property, and its potential mechanism is associated with NF-κB and MAPKs signaling pathways.