The herbal medicine rikkunshito exhibits strong and differential adsorption properties for bile salts

Abstract

Abstract. 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.

Higher Fecal Bile Acid Hydrophobicity Is Associated with Exacerbation of Dextran Sodium Sulfate Colitis in Mice

“…It seems, however, that high doses of fish oil may adversely affect experimental colitis. Fiber sources have been reported to bind bile acids differently (39), which may affect development of colitis during a fish oil diet. The only study reporting a preventive effect for fish oil (33) used a purified diet containing cellulose, similarly to the present study.…”

Randomized clinical trial: rikkunshito in the treatment of functional dyspepsia—a multicenter, double‐blind, randomized, placebo‐controlled study

“…25 Araki et al reported that rikkunshito strongly absorbed hydrophobic bile salts. 26 As hydrophobic bile salts are known to induce oxidative stress and inflammation in the upper gastrointestinal tract, decreased levels of these might improve visceral hypersensitivity in the stomach.…”

Clinical characteristics of elderly patients with proton pump inhibitor-refractory non-erosive reflux disease from the G-PRIDE study who responded to rikkunshito

“…Araki et al showed that RKT can potently absorb bile salts [23]. In addition, RKT improved acid regurgitation-associated signs through prevention of both decreases in the tight junction protein and increases in the intercellular space of the epithelial mucosa in a rat reflux esophagitis model [24].…”