title: Neferine, a bisbenzylisoquinline alkaloid attenuates bleomycin-induced pulmonary fibrosis.
abstract: In this study, we evaluated the potential anti-fibrotic 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+/-97.17 microg/lung and 269.74+/-40.92 microg/lung) compared to sham group (170.78+/-76.46 microg/lung and 191.24+/-60.45 microg/lung), and the hydroxyproline was significantly suppressed (193.07+/-39.55 microg/lung and 201.08+/-71.74 microg/lung) by neferine administration (20mg/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 a significant increase in malondialdehyde (MDA) levels and myeloperoxidase (MPO) activity on the 7th and 14th days. However, neferine reversed the decrease in SOD activity as well as the increase in MDA and MPO activity. Enzyme-linked immunosorbent assay and radio-immunity assay showed that treatment with neferine alleviated bleomycin-induced increase of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and endothelin-1 in plasma or in tissue. Additionally, neferine blocked bleomycin-induced increases of NF-kappaB in nuclear extracts and TGF-beta(1) in total protein extracts of murine RAW264.7 macrophages. In summary, neferine attenuates bleomycin-induced 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-kappaB inhibition.
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Libo
authors.initials: L
authors.lastname: Zhao
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Chang
authors.forename: Junying
authors.initials: J
authors.lastname: Xu
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Qiuyun
authors.initials: Q
authors.lastname: Guo
authors.forename: Shaohui
authors.initials: S
authors.lastname: Zhang
authors.forename: Wenquan
authors.initials: W
authors.lastname: Wang
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Chen
authors.forename: Jialing
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D044182:Benzylisoquinolines / Q000494:pharmacology* / Q000627:therapeutic use; D001761:Bleomycin / Q000009:adverse effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D044182:Benzylisoquinolines; D016207:Cytokines; D019332:Endothelin-1; D015850:Interleukin-6; D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; C057222:neferine; D006909:Hydroxyproline