Liu Chunfang, Zheng Yanfang, Xu Wen, Wang Hui, Lin Na
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China ; Fujian University of Traditional Chinese Medicine, No. 1, Huatuo Road, Minhoushangjie, Fuzhou 350122, China.
Biomed Res Int. 2014;2014:619465. doi: 10.1155/2014/619465. Epub 2014 Aug 18.
Tannins, a group of major active components of Chinese rhubarb and widely distributed in nature, have a significant antidiarrhoeal activity. Aquaporins (AQPs) 2 and 3 play important roles in regulating water transfer during diarrhoea. The present study aims to determine the effect of the total tannins extract of rhubarb on aquaporins (AQPs) 2 and 3 in diarrhoea mice and HT-29 cells both induced by magnesium sulphate (MgSO4). Our results showed that rhubarb tannins extract (RTE) significantly decreased the faecal water content in colon and evaluation index of defecation of diarrhoea mice. Interestingly, RTE could markedly reduce the mRNA and protein expression levels of AQPs 2 and 3 in apical and lateral mucosal epithelial cells in the colons of diarrhoea mice and HT-29 cells both induced by MgSO4 in a dose-dependent manner. Furthermore, RTE suppressed the production of cyclic monophosphate- (cAMP-) dependent protein kinase A catalytic subunits α (PKA C-α) and phosphorylated cAMP response element-binding protein (p-CREB, Ser133) in MgSO4-induced HT-29 cells. Our data showed for the first time that RTE inhibit AQPs 2 and 3 expression in vivo and in vitro via downregulating PKA/p-CREB signal pathway, which accounts for the antidiarrhoeal effect of RTE.
单宁是大黄的一组主要活性成分，广泛分布于自然界，具有显著的止泻活性。水通道蛋白（AQPs）2和3在腹泻期间调节水转运中起重要作用。本研究旨在确定大黄总单宁提取物对硫酸镁（MgSO4）诱导的腹泻小鼠和HT-29细胞中水通道蛋白（AQPs）2和3的影响。我们的结果表明，大黄单宁提取物（RTE）显著降低了腹泻小鼠结肠中的粪便含水量和排便评估指数。有趣的是，RTE可以剂量依赖性地显著降低MgSO4诱导的腹泻小鼠结肠和HT-29细胞顶端和侧方黏膜上皮细胞中AQPs 2和3的mRNA和蛋白表达水平。此外，RTE抑制了MgSO4诱导的HT-29细胞中环磷酸（cAMP）依赖性蛋白激酶A催化亚基α（PKA C-α）和磷酸化cAMP反应元件结合蛋白（p-CREB，Ser133）的产生。我们的数据首次表明，RTE通过下调PKA/p-CREB信号通路在体内和体外抑制AQPs 2和3的表达，这解释了RTE的止泻作用。
