Mechanisms involved in the muscle relaxing effects of STW 5 in guinea pig stomach.

INTRODUCTION: The herbal preparation STW 5 ameliorates functional dyspepsia partly by relaxing smooth muscle of the proximal stomach, thus improving gastric accommodation. We explored the unknown pathways responsible for this effect by testing targets known to modulate gastric smooth muscle relaxation. METHODS: STW 5-induced relaxation of smooth muscle strips from guinea pig gastric corpus before and after pharmacological interventions were recorded with force transducers in an organ bath. ORAI1 mRNA expression was tested in the proximal stomach. KEY RESULTS: Blockade of Ca2+ -activated K+ and Cl- channels, voltage-gated L- or T-type Ca2+ channels, TRPA1-, TRPV1-, adenosine or 5-HT4 receptors, antagonizing ryanodine receptors, inhibiting cyclooxygenase or sarcoplasmic reticulum calcium ATPase did not affect STW 5-evoked relaxation. Likewise, protein-kinase A or G were not involved. However, the relaxation evoked by STW 5 was significantly reduced by phorbol-12-myristat-13-acetat, an activator of protein-kinase C, by 2- aminoethyldiphenylborinate, an inhibitor of the IP3 receptor-mediated Ca2+ release from the sarcoplasmic reticulum or by SKF-96365, a nonselective store-operated calcium entry (SOCE) blocker. Furthermore, the mixed TRPC3/SOCE inhibitor Pyr3, but not the selective TRPC3 blocker Pyr10, reduced the effect of STW 5. Finally, BTP2, a potent blocker of ORAI-coupled SOCE, almost abolished STW 5-evoked relaxation. Expression of ORAI1 could be demonstrated in the corpus/fundus. CONCLUSIONS & INFERENCES: STW 5 inhibited SOCE, most likely ORAI channels, which are modulated by IP3- and PKC-dependent mechanisms. Our findings impact on the design of drugs to induce muscle relaxation and help identify phytochemicals with similar modes of actions to treat gastrointestinal disturbances.

Functional gastrointestinal disorders in children: Effectivity, safety, and tolerability of the herbal preparation STW-5 (Iberogast®) in general practice.

BACKGROUND: Functional gastrointestinal disorders (FGIDs) of the upper and lower digestive system in children and adolescents present with heterogeneous gastrointestinal symptoms and are a common reason for specialist consultations. The herbal medicinal preparation STW-5 has already shown efficacy and safety in clinical studies with more than 7000 adult participants suffering from functional dyspepsia (FD) or irritable bowel syndrome (IBS). Here, we evaluate with a prospective observational study the effectivity and safety of STW-5 in children with FGID under real-life conditions and interpret these data versus the background of controlled clinical studies in a predominantly adult population. METHODS: This prospective observational study included 980 children (age 3-14 years) with FGID. For inclusion, Rome III criteria were recommended to apply. The inclusion of the patients for treatment with STW-5 followed routine clinical practice. Patients were treated for approximately 1 week. The presence and severity of symptoms was documented at the study start and at the end of treatment period utilizing the adapted gastrointestinal symptom score (GIS). Other target parameters included global effectivity and tolerability assessments as well as adverse events. RESULTS: The average patient age was 7.6 ± 2.9 years. Most of the patients were treated for IBS (n = 418; 43 %) or FD (n = 259; 26 %), with a mean baseline GIS of 16.1 ± 8.9. During the treatment period, the GIS decreased 76 % to 3.8 ± 4.2. The decrease in symptoms was similar for different age groups, gender, and indications. Patients with a shorter duration of complaints had a lower GIS at study end (p < 0.0001. The global treatment effect was assessed as good or very good by 87-89 % of patients/parents and physicians. Physicians rated the global tolerability as good or very good for 95 % of the patients. Seven patients (0.7 %) reported adverse events. CONCLUSIONS: The treatment effect of STW-5 in this study was in its range comparable to according data from controlled clinical trials with predominantly adult participants.Thus, supporting robustness of these data generated in an uncontrolled observational setting. The results of this observational study indicate that STW-5 may be an effective and well tolerated treatment option also for children with FGIDs.

Iberogast®-Induced Acute Liver Injury-A Case Report.

Alternative medicines such as phytotherapy and herbal preparations have been widely used over the past 5 decades. However, they are still poorly known in Western medicine, and because they are considered as natural products, they are often omitted in the review of medication. One of the most used herbal preparations in Europe is Iberogast®, a formulation of 9 medicinal plant extracts, including Greater Celandine that has proven effective in the treatment of functional dyspepsia and irritable bowel syndrome. Safety and tolerability of Iberogast® were extensively evaluated in double-blind and randomized studies vs placebo, but rare and usually mild adverse symptoms have been reported in the literature. We report a 32-year-old female with no previous medical history who presented to the emergency department with abdominal pain, jaundice, and pruritus. The blood tests revealed an acute severe hepatitis with marked increase of direct bilirubin. After exclusion of other possible acute liver injury etiologies, we retained the diagnosis of Iberogast®-associated drug-induced liver injury. Patient's symptoms resolved spontaneously 5 weeks after treatment interruption. Despite the general safety of Iberogast®, occasional cases of drug-induced liver injury have been documented. Based on these observations, we recommend that the use of herbal and phytotherapeutic products should be part of the standard investigation of the medical history, as they could be relevant information in the diagnosis process of acute liver injury.

Early onset of efficacy in patients with functional and motility-related gastrointestinal disorders : A noninterventional study with Iberogast®.

STW 5 (Iberogast®; Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany) contains nine plant extracts and possesses well-documented overall efficacy in functional gastrointestinal disorders (FGID). Little is known about the onset of symptom relief. Twenty-nine centers in Germany recruited 272 patients with established FGID. These patients were treated with STW 5 for approximately 3 weeks in this noninterventional study. Patients assessed the severity of their gastrointestinal complaints before and at defined times after the intake of STW 5 (10 cm visual analogue scale; VAS). Fifteen minutes after the first dose, the severity of gastrointestinal complaints had decreased by 1.4 cm (mean; initial mean: 5.2 of 10 cm). After 1 h, more than 90% of the maximum effect of 3.2 cm on the 10 cm VAS had been reached. Most patients with symptoms experienced a marked improvement within 5, 15 or 30 min of taking STW 5. Absolute improvements were larger in patients with more pronounced baseline complaints. Subgroups with upper (80% of the study population) and lower FGID (20%) did not present major differences. Neither did subgroups by age and duration of complaints. Treatment with STW 5 resulted in rapid improvement of symptoms.

The treatment of gastroparesis, constipation and small intestinal bacterial overgrowth syndrome in patients with Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) affects the nerves of the entire gastrointestinal (GI) tract and may result in profound gastrointestinal (GI) dysfunction leading to poor patient outcomes. Common GI disturbances in patients with PD include gastroparesis (GP), constipation and small intestinal bacterial overgrowth syndrome (SIBO). In particular, GP is difficult to treat due to the limited options available and precautions, contraindications and adverse effects associated with the approved treatments. Moreover, some commonly used medications can worsen pre-existing PD. AREAS COVERED: Our review will focus on treatment options for GP and SIBO with motilin agonists, dopamine receptor antagonists, Ghrelin agonists muscarinic agonists, 5-HT4 receptor agonists, antibiotics, probiotics and herbal formulation such as iberogast. Constipation occurs in the majority of patients with PD and fortunately many treatments are now available. Our review is based on original papers or reviews selected from PUBMED search and Cochrane reviews. EXPERT OPINION: Motility disorders of the GI tract are found frequently in patients with PD and treating the underlying GI disorders caused by PD with various prokinetics and laxatives is paramount in achieving improvements in patient's motor function. Various prokinetics and laxatives are now available to provide some relief of the GI morbidity caused by PD leading even to better absorption of even the PD treatments.

Clinical and structural effects of traditional Chinese medicine and the herbal preparation, Iberogast, in a rat model of ulcerative colitis.

Plant-sourced formulations such as Iberogast and the traditional Chinese medicine formulation, Cmed, purportedly possess anti-inflammatory and radical scavenging properties. We investigated Iberogast and Cmed, independently, for their potential to decrease the severity of the large bowel inflammatory disorder, ulcerative colitis. Sprague Dawley rats (n = 8/group) received daily 1 mL gavages (days 0-13) of water, Iberogast (100 µL/200 µL), or Cmed (10 mg/20 mg). Rats ingested 2% dextran sulfate sodium or water ad libitum for 7 days commencing on day 5. Dextran sulfate sodium administration increased disease activity index scores from days 6 to 12, compared with water controls (P < .05). On day 10, 200 µL Iberogast decreased disease activity index scores in colitic rats compared with colitic controls (P < .05). Neither Iberogast nor Cmed achieved statistical significance for daily metabolic parameters or colonic crypt depth. The therapeutic effects of Iberogast and Cmed were minimal in the colitis setting. Further studies of plant extracts are required investigating greater concentrations and alternative delivery systems.