Double-blind, randomized, 8-week multicenter study of the efficacy and safety of STW 5-IIversus placebo in functional dyspepsia.

Background and Aim: Herbal products are widely used to treat patients with disorders of gut brain interaction but clinical efficacy and safety data for treatments lasting >4 weeks are widely lacking. We evaluated the efficacy and safety of 8 weeks of treatment with the herbal combination product STW 5-II for patients with functional dyspepsia (FD) meeting Rome II criteria. We also conducted a post hoc analysis including patients meeting Rome IV criteria for FD and evaluated the effect of the G-protein beta 3 (GNB3) subunit polymorphism (C825T) on therapeutic response. Methods: This multicenter, placebo-controlled, double-blind study included 272 FD patients meeting Rome II criteria in the intention-to-treat cohort and 266 meeting Rome IV criteria. We used the validated Gastrointestinal Symptom Score (GIS) to assess GI symptoms, defining response rate as the proportion of patients with ≥50% GIS improvement in at least three of four assessments. Results: After 8 weeks, the response rate was significantly higher in the STW 5-II group versus placebo (61.2% vs 45.1%, P = 0.008). Mean GIS non-significantly improved with STW 5-II treatment (7.9 ± 4.41 vs 6.7 ± 4.91 with placebo; P = 0.07). In the Rome IV subgroup analysis, STW 5-II yielded a better response rate (P = 0.01) versus placebo and greater postprandial distress symptom improvement (P = 0.04) versus placebo. Safety parameters did not differ between groups, and GNB3 status was not linked with therapeutic response. Conclusion: STW 5-II is efficacious, with no observed safety signals at up to 8 weeks of treatment in patients with FD meeting Rome II or IV criteria.

Efficacy and Safety of STW 5-II for Functional Dyspepsia Treatment: A Patient Data-Based Meta-Analysis.

INTRODUCTION: Functional dyspepsia (FD) is a chronic relapsing gastroduodenal disorder with limited treatment options. Herbal products, like the six-herb combination STW 5-II, can target multiple FD gastrointestinal symptoms. In this meta-analysis, we evaluated the efficacy and safety of STW 5-II for overall FD, and key symptoms, based on Rome IV criteria. METHODS: We systematically screened the literature for randomized controlled clinical studies testing STW 5-II in FD. Meta-analysis was performed using data from individual patients with at least one key FD symptom (fullness, early satiety, or epigastric pain) of at least moderate severity at baseline. ANCOVA-based meta-analyses were performed on improvements in the total symptom sum score, and single symptoms, after 4 and 8 weeks. Safety data were analyzed by calculating odds ratios for all adverse events. RESULTS: Four randomized controlled trials, including 613 patients, were identified, and two were eligible for efficacy analysis. STW 5-II significantly improved the FD symptom sum score (mean difference of 1.74 after 4 weeks and 2.07 after 8 weeks) and key FD symptoms of fullness (0.28 and 0.29), early satiety (0.25 and 0.26), and epigastric/upper abdominal pain (0.26 and 0.3). Treatment-related or severe adverse events did not differ between STW 5-II and placebo. CONCLUSION: The results support that STW 5-II significantly improves FD symptoms after 4 and 8 weeks of treatment with no difference in relation to safety signals compared to placebo. Thus, STW 5-II can be considered an effective and safe treatment option for FD.

Anti-inflammatory and Anti-oxidative Effects of Phytohustil® and Root Extract of Althaea officinalis L. on Macrophages in vitro.

INTRODUCTION: The medicinal plant marshmallow Althaea officinalis L. (A. officinalis), is used for the treatment of cough since centuries. Application of medicinal extracts of marshmallow roots shows immediate effects like a protective film on the inflamed mucosa. Because the soothing layer reduce irritation of the mucous system, a faster regeneration is supported by defense mechanisms required to protect the respiratory tract from environmental injury. Macrophages (MΦ), which belong to a group of multipurpose defensive cells, provide the first line of defense against mucosal invasive pathogens. The present study was performed to investigate, whether the herbal medicinal product has anti-inflammatory or anti-oxidative effects on pro-inflammatorily activated MΦ or after oxidative stress induction. Special attention should be payed to elucidate the effects of A. officinalis on the mechanism of intracellular defense as well as on migratory capacity of the MΦ. RESULTS: Treatment of PMA-differentiated human THP-1 MΦ with Phytohustil® increased their viability without affecting the cell number. Phytohustil® or root extracts of A. officinalis (REAo) - an active component of Phytohustil® - were able to protect human MΦ against H2O2-induced cytotoxicity and H2O2-induced ROS production. Phytohustil®, REAo or diclofenac used as anti-inflammatory reference substance, inhibited the LPS-induced release of tumor necrosis factor-alpha (TNF-α) as well as of IL6 in MΦ. Treatment with Phytohustil®, its excipients or REAo did not impair the mitochondrial membrane potential (MMP). Finally, Phytohustil® and REAo activated the migratory capacity of MΦ. CONCLUSION: The present in vitro investigations indicate protective, i.e., anti-oxidative and anti-inflammatory effects of REAo and Phytohustil®, additionally improving the migratory capacity of MΦ. These antiinflammatory effects were similar or even better than diclofenac. Thus, our data support and may explain the positive effect of Phytohustil® observed in patients during the therapy of inflamed buccal mucosal membranes or treatment of cough.

[Marshmallow Root Extract for the Treatment of Irritative Cough: Two Surveys on Users' View on Effectiveness and Tolerability].

BACKGROUND: Cough preparations containing aqueous marshmallow root extracts (Althaea officinalis) have a long history as medicinal products in Germany. The aim of the 2 prospective, non-interventional surveys reported here was to create a better documentation of the users' impression of the effectiveness and tolerability, and user satisfaction. METHODS: Consumers (n = 822) buying either lozenges or syrup of the aqueous marshmallow root extract STW42 to treat their dry cough were recruited in pharmacies in 2 independently performed surveys. They were asked to fill in a questionnaire covering a treatment duration of 7 days so that the course of symptoms could be documented, and the overall effectiveness, tolerability and satisfaction assessed. RESULTS: This consumer-reported outcome shows that both preparations showed a good effect with respect to the symptomatic treatment of oral or pharyngeal irritation and associated dry cough with a very rapid onset of effects, in the majority of cases within 10 min. The tolerability was very good (with only 3 minor adverse events for the syrup). CONCLUSION: The results of the surveys justify the long-established use of both marshmallow preparations for symptomatic treatment of dry cough.

Phytochemical Characterization of Low Molecular Weight Constituents from Marshmallow Roots (Althaea officinalis) and Inhibiting Effects of the Aqueous Extract on Human Hyaluronidase-1.

Extract RE was obtained from the roots of Althaea officinalis in a yield of 8.1%, related to the dried plant material, by extraction with MeOH-H2O (1:1), followed by precipitation with EtOH to remove high molecular weight constituents. Phytochemical investigation of RE revealed the presence of N-phenylpropenoyl-l-amino acid amides 1-5, 8% glycine betaine 6, about 9% total amino acids with proline as the main compound, and about 61% mono- and oligomeric carbohydrates with sucrose as the main compound. Further fractionation revealed the presence of a hypolaetin diglycoside (12) and four hypolaetin glycosides (7-9 and 11) with O-sulfocarbohydrate moieties; additionally, 4'-O-methylisoscutellarein-8-O-ß-d-(3″-O-sulfo)glucuronopyranoside (10) and the diglycosylated coumarin haploperoside D (13) were identified. The hypolaetin-O-sulfoglycosides 7-10 are new natural products. RE inhibited the enzymatic activity of surface-displayed human hyaluronidase-1 on Escherichia coli F470 cells with an IC50 of 7.7 mg/mL. RE downregulated mRNA expression of hyal-1 in HaCaT keratinocytes at 125 and 250 µg/mL, respectively. These data contribute to a deeper phytochemical understanding of marshmallow root extracts and to the positive influence of extracts used for therapy of irritated and inflamed buccal tissue and cough.