title: Protective effects of neferine on amiodarone-induced pulmonary fibrosis in mice.
abstract: The effects of neferine, a bisbenzylisoquinline alkaloid extracted from the Chinese traditional medicine seed embryo of Nelumbo nucifera Gaertn, on amiodarone-induced pulmonary fibrosis in mice were evaluated. Adult Kunming mice were induced to develop pulmonary fibrosis through intratracheal instillation of amiodarone (6.25 mg/kg) on the 1st, 3rd and 5th day. Mice were treated orally with saline, neferine (20 mg/kg), prednisolone (15 mg/kg), pirfenidone (100 mg/kg) twice a day after the third amiodarone instillation. On Day 21, all the lung tissues were collected for hydroxyproline measurement and the histological examination by hematoxylin-eosin and Masson staining. All the blood sample were collected for surfactant protein-D (SP-D) levels assay, Th1/Th2 balance valuation, CD4+CD25+ regulatory T cells (Tregs) analysis by Enzyme-linked immunosorbent assay and flow cytometry. Our data showed that neferine significantly restored the significant reductions in body weights, the increased levels of lung index and hydroxyproline, the abnormal histological findings, the serum SP-D increase, the Th1/Th2 imbalance by decreasing IL-4 and increasing IFN-γ levels and the increases in the population of CD4+CD25+ Tregs associated with amiodarone instillation in mice. Similar changes were also observed in the prednisolone or pirfenidone treated mice. In conclusion, these results indicated that neferine possessed a significant inhibitory effect on amiodarone-induced pulmonary fibrosis, probably due to its properties of anti-inflammation, SP-D inhibition and restoring increased CD4+CD25+ Tregs which may modulate Th1/Th2 imbalance by suppressing Th2 response (from Th2 polarity toward a Th1 dominant response).
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
authors.forename: Chang-He
authors.initials: CH
authors.lastname: Niu
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Jing-Di
authors.initials: JD
authors.lastname: Liu
authors.forename: Jia-Ling
authors.initials: JL
authors.lastname: Wang
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Xiao
mesh_terms: D000638:Amiodarone / Q000009:adverse effects*; D000818:Animals; D044182:Benzylisoquinolines / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D006909:Hydroxyproline / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D044182:Benzylisoquinolines; D053645:Interleukin-2 Receptor alpha Subunit; D037663:Pulmonary Surfactant-Associated Protein D; C057222:neferine; D000638:Amiodarone; D006909:Hydroxyproline
keywords: Amiodarone; CD4+CD25+ regulatory T cells; Neferine; Pulmonary fibrosis; Surfactant protein-D; Th1/Th2 balance