Inhibitory effects of citrus extracts on the experimental pulmonary fibrosis.

ABSTRACT

AIM OF THE STUDY A Chinese herbal formula, Hu-qi-yin possessed an anti-pulmonary fibrosis effect. Pericarp of Citrus reticulata, one of the herbal drugs contained in this formula showed the most potent inhibitory activity on the proliferation of human embryonic lung fibroblasts (HELF). The present study was designed to clarify the active principles responsible for the activity and further explore the anti-pulmonary fibrosis effect in vivo. MATERIALS AND METHODS: The water, 75% ethanol and flavonoids-enriched extracts of Citrus reticulata were prepared and screened for their anti-proliferation activity using HELF culture system. The ethanol extract was further administered orally at doses of 100 and 200 mg/(kg day) to bleomycin (BLM)-induced pulmonary fibrosis rats. The analyses of the rat body weight, hydroxyproline levels in serum and lung, scores of alveolitis and fibrosis, as well as the expression of transforming growth factor-beta(1) (TGF-beta(1)) at the protein and the messenger ribonucleic acid (mRNA) levels in lung were performed. RESULTS: The ethanol extract showed the strongest inhibitory activity on HELF proliferation. Further research using BLM-induced rat model revealed that the ethanol extract at the doses of 100 and 200 mg/(kg day) caused a marked increase of body weight at first 7 days, significantly lowered the hydroxyproline levels in lung, greatly improved the pathologic scores, as well as inhibited the overexpressions of TGF-beta(1) protein and mRNA. CONCLUSIONS: The results suggest that the ethanol extract of Citrus reticulata has anti-pulmonary fibrosis effects and might have a great potential for the treatment of fibrosis of lung.