Environmental Toxicology / Volume 34, Issue 5 / p.

610-625

RESEARCH ARTICLE

Chemopreventive efficacy zingerone (4-[4-hydroxy-3-methylphenyl] butan-2-one)

in experimental colon carcinogenesis in Wistar rats

Majid Ahmad Ganaie Abdulaziz Al SaeedanHassan MadhkaliBasit Lateef JanTanvir Khatlani

Ishfaq Ahmad SheikhMuneeb U. RehmanKhalida Wani

First published: 05 February 2019

https://doi.org/10.1002/tox.22727
Citations: 14

Funding information: Deanship of Scientific Research at Prince Sattam Bin Abdulaziz University,
Grant/Award Number: 2016/03/6564

Abstract
Colorectal cancer is one of the most common cancers worldwide. Development of naturally
occurring inexpensive and safe alternatives can be effective in suppressing colon related
proliferations. Zingerone (4-[4-hydroxy-3-methylphenyl] butan-2-one), a polyphenolic
alkanone of ginger, has massive pharmacological properties and thus can be used as
promising candidate against various ailments. In the current study, we aimed at
demonstrating the protective effect of zingerone against experimental colon carcinogenesis
and elucidating its possible mechanism by studying inflammatory and Nrf-2 signaling
cascade. Four groups of animals (I-IV) were made with six animals each. Group I (control)
was given normal saline orally. Group II was given 1,2-dimethylhydrazine (DMH) at the dose
rate of 20 mg/kg body weight. Group III and IV were treated with DMH at the dose rate of 20 
mg/kg body weight and also received oral treatment of zingerone at a dose rate of 50 and
100 mg/kg body weight, respectively, for first 5 weeks and animals were euthanized after 16 
weeks. Our results reveal that DMH treated rats exhibited elevated ROS and MDA levels,
increased activity of cytochrome P450 2E1 and serum marker enzyme carcinoembreyonic
antigen (CEA), increased no of aberrant crypts of foci (ACF), and elevated expression of
inflammatory and proliferative proteins. Nrf-2 was downregulated by DMH treatment.
Treatment with zingerone to DMH treated rats, resulted in alterations in the activity of the
cytochrome P450 2E1 and CEA. In addition, immunostaining of NF-kB-p65, COX-2, iNOS, and
PCNA, Ki-67 was suppressed by zingerone. Furthermore, zingerone administration also
attenuated the level of IL-6 and TNF-α and it also helps in preserving mucous layer. Thus,
zingerone could be considered as a good chemopreventive agent in experimental model of
colon carcinogenesis. Further studies are required to study other pathways involved in
colon carcinogenesis and their modulation buy zingerone.

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