Kai Zhou1, Rui Cheng1, Bei Liu1, Lei Wang1, Haifeng Xie2, Chaofeng Zhang3. 1. State Key Laboratory of Natural Medicines, Department of Traditional Chinese Medicines, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China. 2. Chengdu Biopurity Phytochemicals Ltd., Chengdu, 611131, PR China. 3. State Key Laboratory of Natural Medicines, Department of Traditional Chinese Medicines, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China. Electronic address: zhangchaofeng@cpu.edu.cn.
Abstract
BACKGROUND: Despite the higher morbidity of ulcerative colitis (UC), available treatments remain unsatisfactory in recent years. A natural flavone eupatilin (Eup) is known to inhibit the intestinal contraction. PURPOSE: The protective role of Eup in intestinal inflammation remains unclear. This study attempted to determine the bioactivity of Eup against colitis and clarify the mechanism of action. STUDY DESIGN: The in vitro effects of Eup on lipopolysaccharide-induced human THP-M macrophage activation and tumour necrosis factor-α (TNF-α)-damaged intestinal epithelial (NCM460) cells were explored to clarify its potential protective effects. Then, the alleviative efficacy of Eup was established in dextran sodium sulphate (DSS)-induced mice colitis. METHODS: Pathological diagnosis, immunohistochemical staining, and reverse transcriptase PCR analysis as well as western blot analysis were employed in the current study. RESULTS: Eup clearly inhibited inflammatory responses in LPS-stimulated macrophages. Eup also clearly stabilized colonic epithelia by down-regulating overexpression of tight junction proteins and NADPH oxidases 4 (NOX4), and by promoting AMP-activated protein kinase (AMPK) activation in TNF-α-stimulated NCM460 cells. In addition, in vivo study demonstrated that Eup treatment clearly ameliorated the symptoms and pathologic changes of colitis mice. The therapeutic effect of Eup was found to be reduced when compound C (an AMPK pharmacological inhibitor) was given to mice. CONCLUSION: The study successfully demonstrated that Eup ameliorated DSS-induced mice colitis by suppressing inflammation and maintaining the integrity of the intestinal epithelial barrier via AMPK activation. The results provide valuable guidance for using Eup in UC treatment.
BACKGROUND: Despite the higher morbidity of ulcerative colitis (UC), available treatments remain unsatisfactory in recent years. A natural flavone eupatilin (Eup) is known to inhibit the intestinal contraction. PURPOSE: The protective role of Eup in intestinal inflammation remains unclear. This study attempted to determine the bioactivity of Eup against colitis and clarify the mechanism of action. STUDY DESIGN: The in vitro effects of Eup on lipopolysaccharide-induced human THP-M macrophage activation and tumour necrosis factor-α (TNF-α)-damaged intestinal epithelial (NCM460) cells were explored to clarify its potential protective effects. Then, the alleviative efficacy of Eup was established in dextran sodium sulphate (DSS)-induced micecolitis. METHODS: Pathological diagnosis, immunohistochemical staining, and reverse transcriptase PCR analysis as well as western blot analysis were employed in the current study. RESULTS: Eup clearly inhibited inflammatory responses in LPS-stimulated macrophages. Eup also clearly stabilized colonic epithelia by down-regulating overexpression of tight junction proteins and NADPH oxidases 4 (NOX4), and by promoting AMP-activated protein kinase (AMPK) activation in TNF-α-stimulated NCM460 cells. In addition, in vivo study demonstrated that Eup treatment clearly ameliorated the symptoms and pathologic changes of colitismice. The therapeutic effect of Eup was found to be reduced when compound C (an AMPK pharmacological inhibitor) was given to mice. CONCLUSION: The study successfully demonstrated that Eup ameliorated DSS-induced micecolitis by suppressing inflammation and maintaining the integrity of the intestinal epithelial barrier via AMPK activation. The results provide valuable guidance for using Eup in UC treatment.
Authors: Hilda Vargas-Robles; Karla Fabiola Castro-Ochoa; Alí Francisco Citalán-Madrid; Michael Schnoor Journal: World J Gastroenterol Date: 2019-08-14 Impact factor: 5.742