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: Libo Zhao, Xiaomin Wang, Qing Chang, Junying Xu, Ying Huang, Qiuyun Guo, Shaohui Zhang, Wenquan Wang, Xiujuan Chen, Jialing Wang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 627 Issue 1-3 Pg. 304-12 (Feb 10 2010) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 19909737 (Publication Type: Journal Article)
• Copyright: Copyright (c) 2009 Elsevier B.V. All rights reserved.

Chemical References

• Benzylisoquinolines
• Cytokines
• Endothelin-1
• Interleukin-6
• NF-kappa B
• Transforming Growth Factor beta1
• Tumor Necrosis Factor-alpha
• Bleomycin
• neferine
• Hydroxyproline

Topics

• Animals
• Benzylisoquinolines (pharmacology, therapeutic use)
• Bleomycin (adverse effects)
• Cell Line
• Cell Proliferation (drug effects)
• Cytokines (metabolism)
• Endothelin-1 (metabolism)
• Gene Expression Regulation (drug effects)
• Hydroxyproline (metabolism)
• Inflammation (drug therapy, metabolism)
• Interleukin-6 (metabolism)
• Mice
• NF-kappa B (metabolism)
• Oxidative Stress (drug effects)
• Pulmonary Fibrosis (chemically induced, drug therapy, metabolism, pathology)
• Transforming Growth Factor beta1 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)