Neferine suppresses diethylnitrosamine-induced lung carcinogenesis in Wistar rats

Abstract Neferine is a bisbenzylisoquinoline alkaloid isolated from the embryos of lotus which has attracted attention for its anti-inflammatory and anti-cancer activities. The aim of this study was to evaluate the anti-cancer effect of neferine against diethylnitrosamine (DEN)-induced lung carcinogenesis in Wistar rats and to explore the underlying molecular mechanism. DEN-administration induced oxidative stress as indicated by alterations in the levels of pulmonary reactive-oxygen species, lipid peroxidation, protein carbonyl content and antioxidant status whereas treatment with neferine restored cellular normalcy, highlighting the antioxidant potential of neferine in mitigating the oxidative stress-mediated damage produced during DEN-induced lung carcinogenesis. Histopathological analysis showed disorganized alveolar structure, thickened alveolar wall, infiltration of inflammatory cells in DEN-induced rats, the damage was significantly reduced upon neferine treatment. DEN-induced rats exhibited increased expression of NF-κB, COX-2, CYP2E1, VEGF, Bcl-2, PI3K/AKT/mTOR genes and significantly decreased the expression of p53, Bax, caspase-9 and caspase-3 genes. Neferine treatment restored the DEN induced alteration in the expression of these genes. Further, blotting analysis revealed increased expression of NF-κB, COX-2, Bcl-2 and decreased expression of Bax, caspase-9 and caspase-3 proteins in DEN-induced rats. Neferine treatment restored the expression of these proteins in DEN induced lung carcinogenesis.