Neferine,a bisbenzylisoquinline alkaloid attenuates bleomycininduced pulmonary fibrosis in vitro and

来源 :2008中国药学会学术年会暨第八届中国药师周 | 被引量 : 0次 | 上传用户:zhuzhutoutuo
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In this study,we evaluated the potential antifibrotic property of neferine,a bisbenzylisoquinline alkaloid extracted from the seed embryo of Nelumbo mucifera Gaertn. Intratracheal bleomycin administration resulted in pulmonary fibrosis 14 and 21 days posttreatment,as evidenced by increased hydroxyproline content in bleomycin group(255.77±97.17μg/lung and 269.74±40.92μg/lung)compared to sham group(170.78±76.46μg/lung and 191.24±60.45μg/lung),and the hydroxyproline was significantly suppressed(193.07±39.55μg/lung and 201.08±71.74μg/lung)by neferine administration(20 mg/kg,b.i.d). The attenuated-fibrosis condition was also validated by histological observations. Biochemical measurements revealed that bleomycin caused a significant decrease in lung superoxidae dismutase(SOD)activity,which was accompanied with significant increase in malondialdehyde(MDA)levels and myeloperoxiase(MPO)activity on the 7th and 14th day. However,neferine reversed the decrease in SOD activity as well as the increase of MDA and MPO activity. Enzyme-linked immunosorbent assay and radio-immunity assay showed that treatment with neferine alleviated bleomycin induced increase of proinflammatory cytokines such as tumor necrosis factor(TNF)-a,interleukin(IL)-6 and endothelin(ET)1 in plasma or in tissue. Additionally,neferine blocked bleomycin induced increases of NF-?B in nuclear extracts and TGF-? in total protein extracts of murine RAW264.7 macrophages. In conclusion,neferine attenuates bleomycininduced pulmonary fibrosis in vitro and in vivo. The beneficial effect of neferine might be associated with its activities of anti-inflammation,antioxidation,cytokine and NF-?B inhibition.
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