Yu-Sheng Zhang1, Feng Wang2, Shu-Xiang Cui2, Xian-Jun Qu1. 1. a School of Pharmaceutical Sciences, Shandong University , Jinan , China. 2. b Beijing Key Laboratory of Environmental Toxicology , Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University , Beijing , China.
Abstract
Naringin, a natural occurring flavonoid compound, enriches in citrus fruits. We aimed to evaluate the inhibitory effect of naringin on colitis and chronic inflammation-driven carcinogenesis. Male C57BL/6 mice were exposed to AOM/DSS to induce colorectal inflammation and carcinogenesis. Naringin by oral administration prevented AOM/DSS-induced ulcerative colitis and carcinogenesis without significant side effects. Naringin attenuated the severity of colitis and colorectal adenomas through inhibiting myeloid-derived suppressor cells (MDSCs), pro-inflammatory mediators GM-CSF/M-CSF, IL-6 and TNF-α and the NF-κB/IL-6/STAT3 cascades in colorectal tissues. Naringin-treated mice exhibited normalized structures of colorectal tissues. Electron microscopy analysis showed the suppression of robust endoplasmic reticulum (ER) stress-induced autophagy. Naringin inhibited the secretion of the ER-spanning transmembrane proteins, such as GRP78 ATF6, IRE1α and activated PERK phosphorylated eIF-2α and complex of autophagosomes ATG3, ATG5, ATG7, ATG12, ATG16 and ATG16L1 in the colorectal mucosal cells. CONCLUSION: Naringin prevented colitis and colorectal carcinogenesis through suppressing robust ER stress-induced autophagy in colorectal mucosal cells. Naringin could develop a promising therapeutic agent for the prevention of ulcerative colitis and colorectal tumor.
Naringin, a natural occurring flavonoid compound, enriches in citrus fruits. We aimed to evaluate the inhibitory effect of naringin on colitis and chronic inflammation-driven carcinogenesis. Male C57BL/6 mice were exposed to AOM/DSS to induce colorectal inflammation and carcinogenesis. Naringin by oral administration prevented AOM/DSS-induced ulcerative colitis and carcinogenesis without significant side effects. Naringin attenuated the severity of colitis and colorectal adenomas through inhibiting myeloid-derived suppressor cells (MDSCs), pro-inflammatory mediators GM-CSF/M-CSF, IL-6 and TNF-α and the NF-κB/IL-6/STAT3 cascades in colorectal tissues. Naringin-treated mice exhibited normalized structures of colorectal tissues. Electron microscopy analysis showed the suppression of robust endoplasmic reticulum (ER) stress-induced autophagy. Naringin inhibited the secretion of the ER-spanning transmembrane proteins, such as GRP78 ATF6, IRE1α and activated PERK phosphorylated eIF-2α and complex of autophagosomes ATG3, ATG5, ATG7, ATG12, ATG16 and ATG16L1 in the colorectal mucosal cells. CONCLUSION:Naringin prevented colitis and colorectal carcinogenesis through suppressing robust ER stress-induced autophagy in colorectal mucosal cells. Naringin could develop a promising therapeutic agent for the prevention of ulcerative colitis and colorectal tumor.
Authors: Monica Benvenuto; Loredana Albonici; Chiara Focaccetti; Sara Ciuffa; Sara Fazi; Loredana Cifaldi; Martino Tony Miele; Fernando De Maio; Ilaria Tresoldi; Vittorio Manzari; Andrea Modesti; Laura Masuelli; Roberto Bei Journal: Int J Mol Sci Date: 2020-09-10 Impact factor: 5.923
Authors: Peter Kubatka; Alena Mazurakova; Marek Samec; Lenka Koklesova; Kevin Zhai; Raghad Al-Ishaq; Karol Kajo; Kamil Biringer; Desanka Vybohova; Aranka Brockmueller; Martin Pec; Mehdi Shakibaei; Frank A Giordano; Dietrich Büsselberg; Olga Golubnitschaja Journal: EPMA J Date: 2021-10-06 Impact factor: 6.543