Protective mechanism of flavonoids of Oxytropis falcata bunge against IPF

Abstract Aims: Total flavonoids of Oxytropis falcata bunge (FOFB) from plants medicine have anti-inflammatory and anti-fibrotic activities. The present study was to investigate the effect of FOFB on the expression of MCP-1/TNF-α/IL-1β and ICAM-1 proteins in rats with idiopathic pulmonary fibrosis(IPF). Methods: Fifty rats model with IPF was established by a single intratracheal instillation of bleomycin (BLM 5 mg/kg). And 10 rats were taken as the control group without any treatment. After 14 days, model rats were administered the same volume with low dose(100 mg/kg), middle dose (200 mg/kg) and high dose (400 mg/kg) of FOFB, with prednisone acetate tablet (20 mg/kg, PAT group) as the positive drug. The remaining two groups were given the same volume of normal saline once a day for 28 consecutive days. Subsequently, pathological analysis by HE and Masson staining and ultrastructure by transmission electron microscopy were performed. The expressions of cytokines including MCP-1, TNF-α, IL-1β and ICAM-1 were determined by real-time PCR and immunohistochemical staining. Results: Compared with the blank group, severe inflammation and fibrosis were found in the BLM group; The mRNA levels of MCP-1, TNF-α, IL-1β and ICAM-1 were significantly increased in the model group. However, middle or high dose of FOFB and PAT group could significantly decrease infiltration of inflammatory cells, degree of fibrosis, and expression of inflammatory cytokines levels. Conclusion: FOFB can attenuate BLM-induced IPF via inhibiting inflammatory response, reducing inflammatory infiltration, and improving the degree of fibrosis. The mechanism may be related to the inhibition the expression of MCP-1, TNF-α, IL-1β and ICAM-1 proteins.