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

Muneeb U. RehmanMolecular Biology Laboratory, Division of Veterinary Biochemistry, Faculty of Veterinary Sciences and Animal Husbandry Sheri Kashmir University of Agricultural Science and Technology (SKUAST‐K), Alustang, Shuhama Srinagar J&K 190006 IndiaM. R. MirMolecular Biology Laboratory, Division of Veterinary Biochemistry, Faculty of Veterinary Sciences and Animal Husbandry Sheri Kashmir University of Agricultural Science and Technology (SKUAST‐K), Alustang, Shuhama Srinagar J&K 190006 IndiaAdil FarooqRAKCOPS, RAK Medical and Health Sciences University, Ras AL Khaimah 11172 United Arab EmiratesShahzada Mudasir RashidMolecular Biology Laboratory, Division of Veterinary Biochemistry, Faculty of Veterinary Sciences and Animal Husbandry Sheri Kashmir University of Agricultural Science and Technology (SKUAST‐K), Alustang, Shuhama Srinagar J&K 190006 IndiaSheikh Bilal AhmadMolecular Biology Laboratory, Division of Veterinary Biochemistry, Faculty of Veterinary Sciences and Animal Husbandry Sheri Kashmir University of Agricultural Science and Technology (SKUAST‐K), Alustang, Shuhama Srinagar J&K 190006 IndiaRayeesa AliDivision of Veterinary Pathology, Faculty of Veterinary Sciences and Animal Husbandry Sheri Kashmir University of Agricultural Science and Technology (SKUAST‐K), Alustang, Shuhama Srinagar J&K 190006 IndiaIshraq HussainMolecular Biology Laboratory, Division of Veterinary Biochemistry, Faculty of Veterinary Sciences and Animal Husbandry Sheri Kashmir University of Agricultural Science and Technology (SKUAST‐K), Alustang, Shuhama Srinagar J&K 190006 IndiaMubashir Hussain MasoodiDepartment of Pharmaceutical sciences Faculty of Applied Sciences, University of Kashmir, Hazratbal Srinagar J&K 190006 IndiaShowkeen Muzamil BashirMolecular Biology Laboratory, Division of Veterinary Biochemistry, Faculty of Veterinary Sciences and Animal Husbandry Sheri Kashmir University of Agricultural Science and Technology (SKUAST‐K), Alustang, Shuhama Srinagar J&K 190006 IndiaHassan MadkhaliDepartment of Pharmacology, College of Pharmacy Prince Sattam Bin Abdulaziz University Al‐Kharj 11942 Kingdom of Saudi ArabiaMajid Ahmad GanaieDepartment of Pharmacology, College of Pharmacy Prince Sattam Bin Abdulaziz University Al‐Kharj 11942 Kingdom of Saudi Arabia
2018en
ABI

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.

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