Department of Physiology, Graduate School of Medical Sciences, Fukuoka University, Fukuoka, 814-0180, Japan.
Japan Society for the Promotion of Science, Tokyo, 102-0083, Japan.
Sci Rep. 2019 Oct 29;9(1):15554. doi: 10.1038/s41598-019-52171-z.
Japanese Kampo medicines Junchoto and Mashiningan are mixtures of numerous herbal plant extracts and empirically known to exert laxative actions by stimulating fluid secretion in the colonic epithelium. However, it is unknown which and how the herbal components of these crude Kampo drugs are effective to stimulate ion effluxes causing fluid secretion. Here, we selected four herbal components of Junchoto and Mashiningan, Mashinin (MSN), Kyonin (KYN), Tonin (TON), and Daio (DIO), which are putatively laxatives, and examined their effects on the ion channel activity of human colonic epithelial Caco-2 cells. Patch clamp analyses revealed that MSN activated whole-cell current characteristics of the cystic fibrosis transmembrane conductance regulator (CFTR) channel, whereas KYN, TON, and DIO activated the large-conductance and voltage-activated K (BK) channel. Furthermore, electronic cell sizing showed that MSN induced secretory volume decrease (SVD) sensitivity to a CFTR blocker, whereas TON, KYN, and DIO induced SVD sensitivity to a K channel blocker. In conclusion, MSN and TON, KYN, and DIO promote fluid secretion from colonic epithelial cells by activating CFTR and BK channels. Thus, Japanese Kampo medicines, Junchoto and Mashiningan, exert anti-constipation actions by inducing KCl efflux through the combined actions of CFTR- and BK-stimulating herbal components.
日本汉方药“救急汤”和“麻杏甘石汤”是由多种草药提取物混合而成，经验证具有刺激结肠上皮液分泌的通便作用。然而，这些粗制汉方药中的草药成分通过何种方式刺激离子外流导致液体分泌，目前尚不清楚。在这里，我们选择了“救急汤”和“麻杏甘石汤”中的四种草药成分，即麻杏宁（MSN）、苦杏仁苷（KYN）、桃叶珊瑚苷（TON）和大黄酸（DIO），它们被认为是通便剂，并研究了它们对人结肠上皮 Caco-2 细胞离子通道活性的影响。膜片钳分析显示，MSN 激活了囊性纤维化跨膜电导调节剂（CFTR）通道的全细胞电流特性，而 KYN、TON 和 DIO 则激活了大电导和电压激活的钾（BK）通道。此外，电子细胞尺寸测定显示，MSN 诱导了对 CFTR 阻滞剂的分泌体积减少（SVD）敏感性，而 TON、KYN 和 DIO 诱导了对 K 通道阻滞剂的 SVD 敏感性。综上所述，MSN 和 TON、KYN 和 DIO 通过激活 CFTR 和 BK 通道促进结肠上皮细胞的液体分泌。因此，日本汉方药“救急汤”和“麻杏甘石汤”通过 CFTR 和 BK 刺激草药成分的联合作用，诱导 KCl 外流来发挥抗便秘作用。
