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).