Araki Yoshio, Mukaisho Ken-Ichi, Fujiyama Yoshihide, Hattori Takanori, Sugihara Hiroyuki
Departments of Pathology, and.
Exp Ther Med. 2012 Apr;3(4):645-649. doi: 10.3892/etm.2012.478. Epub 2012 Feb 9.
Anti-secretory drugs, particularly proton pump inhibitors (PPIs), are the preferred treatment agents for patients with gastroesophageal reflux disease (GERD). However, refractory GERD, which may manifest as an incomplete or lack of response to PPI therapy, is common. Despite the administration of PPIs for symptomatic control, duodenogastroesophageal reflux (DGER) containing bile is successfully controlled in only one-third of patients. It has previously been reported that the traditional Japanese herbal medicine rikkunshito, which has a prokinetic action on gastric emptying, exhibits clinically therapeutic effects against GERD and DGER that does not respond to PPIs. However, the precise mechanisms responsible for the effects of rikkunshito are still unknown. It has been suggested that the cytotoxicity of the bile salts in the gut lumen is important in GERD and DGER. The aim of the present study was to investigate whether rikkunshito is able to adsorb bile salts through the mechanism by which it ameliorates the symptoms of GERD and DGER. The binding capacities of rikkunshito for bile salts were measured using Langmuir's method. The morphology of rikkunshito was also observed by light microscopy. Rikkunshito strongly adsorbed bile salts. The binding capabilities of rikkunshito were far beyond those of a typical dietary fiber, α-cellulose, or an oral adsorbent. In addition, rikkunshito had higher binding capacities for hydrophobic bile salts as compared with hydrophilic bile salts. In conclusion, rikkunshito has a great capacity to adsorb bile salts. This may be part of the mechanism(s) responsible for the therapeutic effects of rikkunshito in patients with GERD and DGER.
抗分泌药物,尤其是质子泵抑制剂(PPIs),是胃食管反流病(GERD)患者的首选治疗药物。然而,难治性GERD很常见,其表现可能为对PPI治疗反应不完全或无反应。尽管使用PPIs进行症状控制,但仅有三分之一的患者能够成功控制含胆汁的十二指肠胃食管反流(DGER)。此前有报道称,传统的日本草药理气剂对胃排空有促动力作用,对GERD和对PPI无反应的DGER具有临床治疗效果。然而,理气剂产生这些作用的确切机制仍不清楚。有人提出,肠腔内胆盐的细胞毒性在GERD和DGER中很重要。本研究的目的是调查理气剂是否能够通过改善GERD和DGER症状的机制吸附胆盐。使用朗缪尔方法测量理气剂对胆盐的结合能力。还通过光学显微镜观察了理气剂的形态。理气剂能强烈吸附胆盐。理气剂的结合能力远远超过典型的膳食纤维、α-纤维素或口服吸附剂。此外,与亲水性胆盐相比,理气剂对疏水性胆盐具有更高的结合能力。总之,理气剂具有很强的吸附胆盐的能力。这可能是理气剂对GERD和DGER患者产生治疗作用的部分机制。