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柚皮素(4,5,7-三羟基黄酮)通过控制Wistar大鼠结肠中的过度增殖和炎症来抑制癌前病变的发展。

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

作者信息

Rehman Muneeb U, Rahman Mir Manzoor Ur, Farooq Adil, Rashid Shahzada Mudasir, Ahmad Bilal, Bilal Ahmad Sheikh, Ali Rayeesa, Hussain Ishraq, Masoodi Mubashir, Muzamil Showkeen, Madkhali Hassan, Ahmad Ganaie Majid

机构信息

Molecular 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, India.

RAKCOPS, RAK Medical and Health Sciences University, Ras AL, Khaimah, 11172, United Arab Emirates.

出版信息

Environ Toxicol. 2018 Apr;33(4):422-435. doi: 10.1002/tox.22528. Epub 2018 Jan 18.

DOI:10.1002/tox.22528
PMID:29345053
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.

摘要

结肠癌是一个全球性的健康问题,也是最危险的癌症类型之一,对男性和女性都会造成影响。柚皮素(4,5,7-三羟基黄酮)是柑橘类水果中存在的主要黄酮糖苷之一。由于其卓越的药理特性和无毒性质,柚皮素长期以来一直被用于中国传统医学。在本研究中,我们调查了柚皮素对1,2-二甲基肼(DMH)诱导的癌前病变,即异常隐窝灶(ACF)和黏液缺失灶(MDF)的化学预防潜力,以及它在调节Wistar大鼠结肠中的氧化应激、炎症和过度增殖方面的作用。动物被分为五组。在第3 - 5组中,柚皮素以50毫克/千克体重的剂量口服给药,而在第2 - 4组中,DMH以20毫克/千克体重的剂量在腹股沟皮下注射,每周一次,持续5周,10周后对动物实施安乐死。柚皮素的给药改善了DMH诱导的脂质过氧化、活性氧形成、癌前病变(ACF和MDF)的发展,还减少了肥大细胞的浸润,抑制了NF-κB-p65、COX-2、诱导型一氧化氮合酶、增殖细胞核抗原和Ki 67的免疫染色。柚皮素治疗显著降低了肿瘤坏死因子-α的水平,还防止了黏液层的消耗。我们的研究结果表明,柚皮素对DMH诱导的结肠癌发生具有强大的化学预防潜力,但需要进一步研究以阐明柚皮素的确切作用机制。

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