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Food Chem Toxicol. 2019 Jan;123:385-398. doi: 10.1016/j.fct.2018.11.014. Epub 2018 Nov 10.

Neferine suppresses diethylnitrosamine-induced lung carcinogenesis in Wistar rats.

Author information

1
Translational Research Laboratory, Department of Biotechnology, School of Biotechnology and Genetic Engineering, Bharathiar University, Coimbatore, Tamil Nadu, India.
2
Department of Industrial Biotechnology, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India.
3
Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan; School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan.
4
Translational Research Laboratory, Department of Biotechnology, School of Biotechnology and Genetic Engineering, Bharathiar University, Coimbatore, Tamil Nadu, India; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan. Electronic address: vvijayapadma@rediffmail.com.

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-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-κB, 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-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.

KEYWORDS:

Apoptosis; Diethylnitrosamine; Inflammation; Lung cancer; Neferine

PMID:
30423403
DOI:
10.1016/j.fct.2018.11.014
[Indexed for MEDLINE]

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