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

Araki, Yoshio; Mukaisho, Ken‐ichi; Fujiyama, Yoshihide; Hattori, Takanori; Sugihara, Hiroyuki

doi:10.3892/etm.2012.478

Cited by 18 publications

(12 citation statements)

References 35 publications

(40 reference statements)

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Stenman

Holma

Forsgård

et al. 2013

The Journal of Nutrition

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Increased luminal bile acid hydrophobicity is associated with cytotoxicity and has been suggested to contribute to gut barrier dysfunction. The aim of this study was to compare 2 high-fat diets and a low-fat diet as to whether they modify fecal bile acid profile and hydrophobicity and/or susceptibility to dextran sodium sulfate (DSS) colitis in C57Bl/6J mice. Control and DSS-Control groups received a low-fat control diet [5.5% of total energy (E%) soy oil, 4.5 E% lard], and the DSS-Lard (5.5 E% soy oil, 54.5 E% lard) and DSS-Fish oil (5.5 E% soy oil, 27.2 E% lard and 27.2% menhaden oil) groups received high-fat diets. Feces for bile acid analysis were collected after 3-wk feeding, followed by induction of dextran DSS colitis (2 d 5% DSS in drinking water + 2 d tap water). Fecal bile acid hydrophobicity was elevated 76% in the lard group (P = 0.051) and 122% in the fish oil group (P = 0.001) compared with control, indicating potentially increased cytotoxicity. DSS caused severe colitis symptoms, evaluated as rectal bleeding, whereas all the controls were symptom free. The median symptom scores were: DSS-Control, 2.3 (IQR = 0.6, 3.0); DSS-Lard, 0.3 (IQR = 0, 2.3); and DSS-Fish oil, 2.4 (IQR = 1.9, 2.8). The only differences were DSS-Control vs. control (P < 0.001) and DSS-Fish oil vs. control (P < 0.001). Severity of symptoms in all colitic mice was positively correlated with fecal bile acid hydrophobicity (Spearman's ρ = 0.43; P = 0.028) and fecal deoxycholic acid concentration (Spearman's ρ = 0.39; P = 0.048). These results suggest that luminal bile acid modification, induced by altered dietary fat composition, may alter susceptibility to DSS colitis.

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Section: Discussionmentioning

confidence: 99%

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

Stenman

Holma

Forsgård

et al. 2013

The Journal of Nutrition

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Suzuki

Matsuzaki

Fukushima³

et al. 2014

Neurogastroenterology Motil

116

112

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Background Rikkunshito, a standardized Japanese herbal medicine, is thought to accelerate gastric emptying and relieve dyspepsia, although no large‐scale, randomized, placebo‐controlled trials of rikkunshito have been conducted. This study aimed to determine the efficacy and safety of rikkunshito for treating functional dyspepsia (FD). Methods FD patients received 2.5 g rikkunshito or placebo three times a day for 8 weeks in this multicenter, randomized, placebo‐controlled, parallel‐group trial. The primary end point was the proportion of responders at 8 weeks after starting test drug, determined by global patient assessment (GPA). The improvement in four major dyspepsia symptoms severity scale was also evaluated. In addition, plasma ghrelin levels were investigated before and after treatment. Key Results Two hundred forty‐seven patients were randomly assigned. In the eighth week, the rikkunshito group had more GPA responders (33.6%) than the placebo (23.8%), although this did not reach statistical significance (p = 0.09). Epigastric pain was significantly improved (p = 0.04) and postprandial fullness tended to improve (p = 0.06) in the rikkunshito group at week 8. Rikkunshito was relatively more effective among Helicobacter pylori‐infected participants (rikkunshito: 40.0% vs placebo: 20.5%, p = 0.07), and seemed less effective among H. pylori‐uninfected participants (rikkunshito: 29.3% vs placebo: 25.6%, p = 0.72). Among H. pylori‐positive individuals, acyl ghrelin levels were improved just in rikkunshito group. There were no severe adverse events in both groups. Conclusions & Inferences Administration of rikkunshito for 8 weeks reduced dyspepsia, particularly symptoms of epigastric pain and postprandial fullness. (UMIN Clinical Trials Registry, Number UMIN000003954).

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“…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].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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BackgroundThe incidence and severity of gastroesophageal reflux disease (GERD) in Japan tends to increase in elderly women. Rikkunshito (RKT), a traditional Japanese medicine, acts as a prokinetic agent and improves gastric emptying and gastric accommodation. Our previous prospective randomized placebo-controlled study showed that RKT combined with a standard-dose of rabeprazole (RPZ) significantly improved the acid-related dysmotility symptoms (ARD) in elderly patients with proton pump inhibitor (PPI)-refractory non-erosive reflux disease (NERD). This study aimed to evaluate clinical characteristics of elderly PPI-refractory NERD patients with ARD symptoms who responded to RKT.MethodsTwo hundred forty-two patients with PPI-refractory NERD were randomly assigned to 8 weeks of either RPZ (10 mg/q.d.) + RKT (7.5 g/t.i.d.) (RKT group) or RPZ + placebo (PL group). Among them, 95 were elderly (≥65 years) with ARD (RKT group: n = 52; PL group: n = 43). We analyzed the changes using the 12 subscale score of frequency scale for the symptoms of GERD (FSSG) and 15 items of the Gastrointestinal Symptom Rating Scale at 4 and 8 weeks and compared the therapeutic efficacy between the 2 groups.ResultsThere were no marked differences in baseline demographic or clinical characteristics in the 2 groups except for rate of current smoking. The FSSG score (mean ± SD at 0, 4, and 8 weeks) in both the RKT (16.0 ± 7.0; 9.9 ± 8.4; 7.0 ± 6.4) and PL (15.1 ± 6.4; 10.9 ± 6.7, 11.1 ± 8.5) groups significantly decreased after treatment. However, the degree of improvement of total and ARD scores of FSSG after the 8-week treatment was significantly greater in the RKT group than in the PL group. Combination therapy with RKT for 8 weeks showed significant improvement in 3 subscale scores (abdominal bloating, heavy feeling in stomach and sick feeling after meals) of the ARD domain and 1 subscale score (heartburn after meals) of the reflux symptom domain.ConclusionsRKT may be useful for improving GERD symptoms in elderly PPI-refractory NERD patients with ARD. Thus, RKT was particularly effective for resolving postprandial GERD symptoms (heavy feeling in stomach, sick feeling, and heartburn after meals).Trial registration(UMIN000005880)

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

Cited by 18 publications

References 35 publications

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

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

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

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

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