Samuels Tina L, Pearson Amy C S, Wells Clive W, Stoner Gary D, Johnston Nikki
Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Ann Otol Rhinol Laryngol. 2013 Oct;122(10):632-41.
Laryngopharyngeal reflux (LPR) is associated with inflammatory and neoplastic airway diseases. Gastric pepsin internalized by airway epithelial cells during reflux contributes to oxidative stress, inflammation, and carcinogenesis. Several plant extracts and compounds inhibit digestive enzymes and inflammatory or neoplastic changes to the esophagus in models of gastroesophageal reflux. This study examined the potential of chemoprotective phytochemicals to inhibit peptic activity and mitigate pepsin-mediated damage of airway epithelial cells.
Cultured human laryngeal and hypopharyngeal epithelial cells were pretreated with curcumin (10 micromol/L), ecabet sodium (125 microg/mL), and anthocyanin-enriched black-raspberry extract (100 microg/mL) 30 minutes before treatment with pepsin (0.1 mg/mL; 1 hour; pH 7). Controls were treated with media pH 7 or pepsin pH 7 without phytochemicals. Cell damage and proliferative changes were assessed by electron microscopy, cell count, thymidine analog incorporation, and real-time polymerase chain reaction array. Pepsin inhibition was determined by in vitro kinetic assay.
Micromolar concentrations of curcumin, ecabet sodium, and black-raspberry extract inhibited peptic activity and pepsin-induced mitochondrial damage and hyperproliferation. Curcumin abrogated pepsin-mediated depression of tumor suppressor gene expression and altered the subcellular localization of pepsin following endocytosis.
Several phytochemicals inhibit the pepsin-mediated cell damage underlying inflammatory or neoplastic manifestations of LPR. Dietary supplementation or adjunctive therapy with phytochemicals may represent novel preventive or therapeutic strategies for LPR-attributed disease.
喉咽反流（LPR）与气道炎症性疾病和肿瘤性疾病相关。反流期间气道上皮细胞内化的胃蛋白酶会导致氧化应激、炎症和致癌作用。在胃食管反流模型中，几种植物提取物和化合物可抑制消化酶以及食管的炎症或肿瘤性变化。本研究考察了具有化学保护作用的植物化学物质抑制胃蛋白酶活性并减轻其介导的气道上皮细胞损伤的潜力。
在用胃蛋白酶（0.1 mg/mL；1小时；pH 7）处理前30分钟，用姜黄素（10微摩尔/升）、依卡倍特钠（125微克/毫升）和富含花青素的黑树莓提取物（100微克/毫升）对培养的人喉和下咽上皮细胞进行预处理。对照组用pH 7的培养基或不含植物化学物质的pH 7胃蛋白酶处理。通过电子显微镜、细胞计数、胸腺嘧啶核苷类似物掺入和实时聚合酶链反应阵列评估细胞损伤和增殖变化。通过体外动力学测定确定胃蛋白酶抑制作用。
微摩尔浓度的姜黄素、依卡倍特钠和黑树莓提取物可抑制胃蛋白酶活性以及胃蛋白酶诱导的线粒体损伤和过度增殖。姜黄素消除了胃蛋白酶介导的肿瘤抑制基因表达的抑制，并改变了内吞后胃蛋白酶的亚细胞定位。
几种植物化学物质可抑制LPR炎症或肿瘤表现背后的胃蛋白酶介导的细胞损伤。用植物化学物质进行膳食补充或辅助治疗可能代表LPR相关疾病的新型预防或治疗策略。
