Gastroenterology Unit, Department of Clinical and Experimental Medicine, Federico II University of Naples, Italy.
Dig Liver Dis. 2012 Jul;44(7):555-62. doi: 10.1016/j.dld.2012.01.009. Epub 2012 Feb 28.
Searching for alternative therapies that are effective, safe and less expensive of those currently used for ulcerative colitis, we investigated the efficacy of a polyphenol extract from apple in rat colitis.
Rats with trinitrobenzensulphonic acid-induced colitis were treated daily with rectal administration of apple polyphenols 10(-4) M for 14 days. COX-2, TNF-α, tissue transglutaminase and calpain in colon mucosa samples were assessed by reverse transcription-polymerase chain reaction and western blot analyses. To ascertain the role of tissue transglutaminase in mucosal healing, wounded rat fibroblasts were incubated with cystamine (a tissue transglutaminase activity inhibitor).
Colitis was associated with increased COX-2, TNF-α, calpain, and tissue transglutaminase mRNA. The protein expression of COX-2, TNF-α and calpain was increased whilst tissue transglutaminase was decreased. Apple extract treatment reduced the severity of colitis (p<0.05) and restored all the considered biomarkers at the baseline level. Apple polyphenols reduced the degradation of tissue transglutaminase protein occurring through calpain action. Apple polyphenols-treated wounded fibroblast recovered within 24h showing intense immunoreactivity for tissue transglutaminase.
The efficacy of apple extract is mediated by its effects on COX-2 and TNF-α. The unbalance between calpain and tissue transglutaminase may play a role in colonic damage and future therapeutic interventions in ulcerative colitis can target this mechanisms.
为了寻找有效、安全且比目前用于溃疡性结肠炎的疗法更廉价的替代疗法,我们研究了苹果多酚提取物在大鼠结肠炎中的疗效。
采用三硝基苯磺酸诱导的大鼠结肠炎模型,每天经直肠给予苹果多酚 10(-4) M,共 14 天。采用逆转录-聚合酶链反应和 Western blot 分析检测结肠黏膜样本中的 COX-2、TNF-α、组织转谷氨酰胺酶和钙蛋白酶。为了确定组织转谷氨酰胺酶在黏膜愈合中的作用,用半胱胺(一种组织转谷氨酰胺酶活性抑制剂)孵育创伤大鼠成纤维细胞。
结肠炎与 COX-2、TNF-α、钙蛋白酶和组织转谷氨酰胺酶 mRNA 的增加有关。COX-2、TNF-α和钙蛋白酶的蛋白表达增加,而组织转谷氨酰胺酶的表达减少。苹果提取物治疗减轻了结肠炎的严重程度(p<0.05),并使所有考虑的生物标志物恢复到基线水平。苹果多酚通过钙蛋白酶作用减少了组织转谷氨酰胺酶蛋白的降解。经苹果多酚处理的创伤性成纤维细胞在 24 小时内恢复,组织转谷氨酰胺酶的免疫反应性强烈。
苹果提取物的疗效是通过其对 COX-2 和 TNF-α 的作用介导的。钙蛋白酶和组织转谷氨酰胺酶之间的失衡可能在结肠损伤中起作用,溃疡性结肠炎的未来治疗干预可以针对这些机制。