Chemopreventive efficacy zingerone (4‐[4‐hydroxy‐3‐methylphenyl] butan‐2‐one) in experimental colon carcinogenesis in Wistar rats
2019
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-? 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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