Neferine suppresses diethylnitrosamine-induced lung carcinogenesis in Wistar rats

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-induced oxidative stress is mediated by alterations in the levels of pulmonary reactive-oxygen species, lipid peroxidation, protein carbonyl content and antioxidant status. Thus, 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 gene expression of NF-kappa B, COX-2, CYP2E1, VEGF, Bcl-2, PI3K/AKT/mTOR and significantly decreased the gene expression of p53, Bax, caspase-9 and caspase-3. Neferine treatment restored the DEN- induced alteration of these gene expression levels. Further, blotting analysis also revealed increased expression of NF-kappa B, 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.