Naringenin (4,5,7‐trihydroxyflavanone) suppresses the development of precancerous lesions via controlling hyperproliferation and inflammation in the colon of Wistar rats

Abstract

Colon cancer is a world-wide health problem and one of the most dangerous type of cancer, affecting both men and women. Naringenin (4, 5, 7-trihydroxyflavanone) is one of the major flavone glycoside present in citrus fruits. Naringenin has long been used in Chinese's traditional medicine because of its exceptional pharmacological properties and non-toxic nature. In the present study, we investigated the chemopreventive potential of Naringenin against 1,2-dimethyhydrazine (DMH)-induced precancerous lesions, that is, aberrant crypt foci (ACF) and mucin depleted foci (MDF), and its role in regulating the oxidative stress, inflammation and hyperproliferation, in the colon of Wistar rats. Animals were divided into five groups. In groups 3-5, Naringenin was administered at the dose of 50 mg/kg b. wt. orally while in groups 2-4, DMH was administered subcutaneously in the groin at the dose of 20 mg/kg b. wt. once a week for first 5 weeks and animals were euthanized after 10 weeks. Administration of Naringenin ameliorated the development of DMH-induced lipid peroxidation, ROS formation, precancerous lesions (ACF and MDF) and it also reduced the infiltration of mast cells, suppressed the immunostaining of NF-κB-p65, COX-2, i-NOS PCNA and Ki 67 Naringenin treatment significantly attenuated the level of TNF-α and it also prevented the depletion of the mucous layer. Our findings suggest that Naringenin has strong chemopreventive potential against DMH-induced colon carcinogenesis but further studies are warranted to elucidate the precise mechanism of action of Naringenin.

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

“…Methyl free radical generated by metabolism of DMH cause accumulation up of hydroxyl radical or hydrogen peroxide that may contribute to lipid peroxidation or MDA . Lipid peroxidation is a known marker of oxidative stress in colon toxicity and that remarkable elevation in the level of MDA, a lipid peroxidation product, was observed after DMH treatment . Our results corroborated with the previous studies which reveled marked decrease in MDA levels after zingerone treatment (Figure ).…”

“…Recent studies report the role of ROS production including singlet oxygen, hydroperoxides, H 2 O 2 , and O 2 − in origination of DMH toxicity . The present study demonstrated the oxidative damage in colon led by excessive ROS production on DMH exposure.…”

“…The slides were then washed in distilled water and the sections were then counterstained with neutral red (0.5% aqueous solution) for 20 seconds, dehydrated in alcohol and mounted by using mounting media. The slides were then evaluated under the light microscope …”

“…PCNA, a 36 kDa cofactor of DNA polymerase‐δ, is one of the downstream effectors of the activation of MAPK/ERK1/2 signaling and is a reliable molecular biomarker of hyperproliferation. PCNA and Ki67 are frequently studies as markers of cellular proliferation in chemopreventive studies . Expression of both these proliferative markers correlated with the progress of neoplastic disease and are used to assess the hyperproliferative events.…”

Mechanisms associated to apoptosis of cancer cells by phenolic extracts from two canned common beans varieties (Phaseolus vulgarisL.)

“…Quercetin glucosides are also present in Bayo Victoria beans and are related to cytotoxicity of HepG2, PC-3 and HT-29 cancer cell lines (Pan, Zheng, & Ho, 2018). In addition, Bayo Victoria beans have naringenin, which is related to antiproliferative effects in animal models, suppressing the development of cancerous lesions (Rehman et al, 2018).…”