Steigerwald Arzneimittelwerk GmbH

Darmstadt, Germany

Steigerwald Arzneimittelwerk GmbH

Darmstadt, Germany

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Khayyal M.T.,Cairo University | Abdel-Naby D.H.,National Center for Radiation Research And Technology | Abdel-Aziz H.,Steigerwald Arzneimittelwerk GmbH | El-Ghazaly M.A.,National Center for Radiation Research And Technology
Phytomedicine | Year: 2014

Purpose Intestinal mucositis is a common adverse effect in patients undergoing radiotherapy and constitutes a treatment-limiting condition. Since no agents are yet known that can adequately guard against its development, the search continues to find safe and effective measures. The present study was intended to investigate whether the herbal preparation, STW 5, could offer a potentially effective agent in this respect. Methods Intestinal mucositis was induced in rats by exposing them to whole body gamma-irradiation (6 Gy). Rats were treated orally with STW 5 (5 or 10 ml/kg) for five days before and two days after irradiation. One day later, rats were sacrificed and segments of small intestine were examined histologically. Intestinal homogenates and serum samples were used to assess relevant parameters for apoptosis and different markers for inflammation and oxidative stress. Results Exposure to radiation produced dose-dependent extents of intestinal injury associated with apoptotic changes with high radiation levels. Apoptosis was associated with an increase in cytosolic calcium, depletion of mitochondrial cytochrome c, B-cell lymphoma-2 and complex I. Oxidative stress parameters (reduced glutathione, thiobarbituric acid reactive substance and total nitrate/nitrite) were deranged. Inflammation markers (tumor necrosis factor and myeloperoxidase) and indices of intestinal damage (serum diamine oxidase) were increased. STW 5 protected to a large extent against histological changes and counteracted the deranged parameters. Conclusion The findings provide experimental evidence for the potential beneficial use of STW5 in protecting against the development of radiation-induced intestinal mucositis and associated changes in tissue biomarkers. © 2014 The Authors.

Weidner C.,Max Planck Institute for Molecular Genetics | Rousseau M.,Max Planck Institute for Molecular Genetics | Plauth A.,Max Planck Institute for Molecular Genetics | Wowro S.J.,Max Planck Institute for Molecular Genetics | And 3 more authors.
Phytomedicine | Year: 2015

Purpose Efficient strategies for the prevention of colon cancer are extensively being explored, including dietary intervention and the development of novel phytopharmaceuticals. Safe extracts of edible plants contain structurally diverse molecules that can effectively interfere with multi-factorial diseases such as colon cancer. In this study, we describe the antiproliferative and proapoptotic effects of ethanolic lemon balm (Melissa officinalis) leaves extract in human colon carcinoma cells. We further investigated the role of extra- and intracellular reactive oxygen species (ROS). Methods Antitumor effects of lemon balm extract (LBE) were investigated in HT-29 and T84 human colon carcinoma cells. Inhibition of proliferation was analyzed by DNA quantification. The causal cell cycle arrest was determined by flow cytometry of propidium iodide-stained cells and by immunoblotting of cell cycle regulator proteins. To investigate apoptosis, cleavage of caspases 3 and 7 was detected by immunoblotting and fluorescence microscopy. Phosphatidylserine externalization was measured by Annexin V assays. Mechanistic insights were gained by measurement of ROS using the indicator dyes CM-H2DCFDA and Cell ROX Green. Results After 3 and 4 days of treatment, LBE inhibited the proliferation of HT-29 and T84 colon carcinoma cells with an inhibitory concentration (IC50) of 346 and 120 μg/ml, respectively. Antiproliferative effects were associated with a G2/M cell cycle arrest and reduced protein expression of cyclin dependent kinases (CDK) 2, 4, 6, cyclin D3, and induced expression of cyclin-dependent kinase inhibitor 2C (p18) and 1A (p21). LBE (600 μg/ml) induced cleavage of caspases 3 and 7 and phosphatidylserine externalization. LBE-induced apoptosis was further associated with formation of ROS, whereas quenching of ROS by antioxidants completely rescued the colon carcinoma cells from LBE-induced apoptosis. Conclusions Lemon balm (Melissa officinalis) extract inhibits the proliferation of colon carcinoma cells and induces apoptosis through formation of ROS. Taken together, LBE or subfractions thereof could be used for the prevention of colon cancer. © 2015 Elsevier GmbH. All rights reserved.

Kelber O.,Steigerwald Arzneimittelwerk GmbH | Abdel-Aziz H.,Steigerwald Arzneimittelwerk GmbH | Schrenk D.,University of Kaiserslautern
Synergy | Year: 2014

The pharmacology and toxicology of combination medicinal products are preferentially studied using the combination as the test substance, as testing of the isolated constituents does not allow to detect potential sub- or supra-additive effects. This applies as well to combinations of chemically defined pharmaceutically active ingredients as to herbal medicinal products, which typically contain a combination of hundreds or even thousands of constituents as the active substance. © 2014 Elsevier GmbH.

Vissiennon C.,University of Florida | Vissiennon C.,University of Leipzig | Nieber K.,University of Leipzig | Kelber O.,Steigerwald Arzneimittelwerk GmbH | Butterweck V.,University of Florida
Journal of Nutritional Biochemistry | Year: 2012

Several in vivo and in vitro studies have confirmed that flavonols are metabolized by the intestinal microflora to their corresponding hydroxyphenylacetic acids. In this article, a comparison of the anxiolytic activity of the flavonols kaempferol, quercetin and myricetin in the elevated plus maze after oral (po) and intraperitoneal (ip) administration to mice in a dose range of 0.1 to 2.0 mg/kg is presented. In addition, their corresponding metabolites p-hydroxyphenylacetic acid (p-HPAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were tested after intraperitoneal administration. Anxiolytic activity was detected for kaempferol and quercetin only after oral administration. No anxiolytic effects were observed when kaempferol and quercetin were given via the intraperitoneal administration route. The corresponding hydroxyphenylacetic metabolites p-HPAA and DOPAC showed anxiolytic effects after intraperitoneal application. In order to further test the hypothesis that flavonoids are possible prodrugs which require activation by intestinal bacteria, gut sterilization was performed using pretreatment with the antibiotic enrofloxacin (7.5 mg/day, po, for 4 days). After antibiotic treatment, the anxiolytic effect of kaempferol and quercetin disappeared, whereas it was still present for the positive control diazepam. Our results support the hypothesis that flavonoids act as prodrugs which are transformed into their active hydroxyphenylacetic acid metabolites by intestinal microflora. © 2012 Elsevier Inc..

Weidner C.,Max Planck Institute for Molecular Genetics | Weidner C.,Free University of Berlin | Wowro S.J.,Max Planck Institute for Molecular Genetics | Rousseau M.,Max Planck Institute for Molecular Genetics | And 5 more authors.
PLoS ONE | Year: 2013

Given the significant increases in the incidence of metabolic diseases, efficient strategies for preventing and treating of these common disorders are urgently needed. This includes the development of phytopharmaceutical products or functional foods to prevent or cure metabolic diseases. Plant extracts from edible biomaterial provide a potential resource of structurally diverse molecules that can synergistically interfere with complex disorders. In this study we describe the safe application of ethanolic chamomile (Matricaria recutita) flowers extract (CFE) for the treatment and prevention of type 2 diabetes and associated disorders. We show in vitro that this extract activates in particular nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) and its isotypes. In a cellular context, in human primary adipocytes CFE administration (300 μg/ml) led to specific expression of target genes of PPARγ, whereas in human hepatocytes CFE-induced we detected expression changes of genes that were regulated by PPARα. In vivo treatment of insulin-resistant high-fat diet (HFD)-fed C57BL/6 mice with CFE (200 mg/kg/d) for 6 weeks considerably reduced insulin resistance, glucose intolerance, plasma triacylglycerol, non-esterified fatty acids (NEFA) and LDL/VLDL cholesterol. Co-feeding of lean C57BL/6 mice a HFD with 200 mg/kg/d CFE for 20 weeks showed effective prevention of fatty liver formation and hepatic inflammation, indicating additionally hepatoprotective effects of the extract. Moreover, CFE treatment did not reveal side effects, which have otherwise been associated with strong synthetic PPAR-targeting molecules, such as weight gain, liver disorders, hemodilution or bone cell turnover. Taken together, modulation of PPARs and other factors by chamomile flowers extract has the potential to prevent or treat type 2 diabetes and related disorders. © 2013 Weidner et al.

Weidner C.,Max Planck Institute for Molecular Genetics | Weidner C.,Free University of Berlin | Wowro S.J.,Max Planck Institute for Molecular Genetics | Freiwald A.,Max Planck Institute for Molecular Genetics | And 4 more authors.
Molecular Nutrition and Food Research | Year: 2014

Over the last decades polyetiological metabolic diseases such as obesity and type 2 diabetes have emerged as a global epidemic. Efficient strategies for prevention and treatment include dietary intervention and the development of validated nutraceuticals. Safe extracts of edible plants provide a resource of structurally diverse molecules that can effectively interfere with multifactorial diseases. In this study, we describe the application of ethanolic lemon balm (Melissa officinalis) leaves extract for the treatment of insulin-resistance and dyslipidemia in mice. We show that lemon balm extract (LBE) activates the peroxisome proliferator-activated receptors (PPARs), which have key roles in the regulation of whole body glucose and lipid metabolism. Application of LBE (0.6 mg/mL) to human primary adipocytes resulted in specific peroxisome proliferator-activated receptor target gene expression. LBE treatment of insulin-resistant high-fat diet-fed C57BL/6 mice (200 mg/kg/day) for 6 weeks considerably reduced hyperglycemia and insulin resistance, plasma triacylglycerol, nonesterified fatty acids and LDL/VLDL cholesterol levels. Taken together, ethanolic lemon balm extract can potentially be used to prevent or concomitantly treat type 2 diabetes and associated disorders such as dyslipidemia and hypercholesterolemia. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Kelber O.,Safety and Interactions of Kooperation Phytopharmaka GbR | Kelber O.,Steigerwald Arzneimittelwerk GmbH | Nieber K.,Safety and Interactions of Kooperation Phytopharmaka GbR | Nieber K.,University of Leipzig | And 2 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2014

In recent popular publications as well as in widely used information websites directed to cancer patients, valerian is claimed to have a potential of adverse interactions with anticancer drugs. This questions its use as a safe replacement for, for example, benzodiazepines. A review on the interaction potential of preparations from valerian root (Valeriana officinalis L. root) was therefore conducted. A data base search and search in a clinical drug interaction data base were conducted. Thereafter, a systematic assessment of publications was performed. Seven in vitro studies on six CYP 450 isoenzymes, on p-glycoprotein, and on two UGT isoenzymes were identified. However, the methodological assessment of these studies did not support their suitability for the prediction of clinically relevant interactions. In addition, clinical studies on various valerian preparations did not reveal any relevant interaction potential concerning CYP 1A2, 2D6, 2E1, and 3A4. Available animal and human pharmacodynamic studies did not verify any interaction potential. The interaction potential of valerian preparations therefore seems to be low and thereby without clinical relevance. We conclude that there is no specific evidence questioning their safety, also in cancer patients. © 2014 Olaf Kelber et al.

Wadie W.,Cairo University | Abdel-Aziz H.,University of Munster | Zaki H.F.,Cairo University | Kelber O.,Steigerwald Arzneimittelwerk GmbH | And 2 more authors.
International Journal of Colorectal Disease | Year: 2012

Purpose An herbal preparation, STW 5, used clinically in functional dyspepsia and irritable bowel syndrome, has been shown to possess properties that may render it useful in inflammatory bowel disease (IBD). The present work was conducted to study its effectiveness in a rat model of IBD. Methods An experimental model reflecting ulcerative colitis in man was adopted, whereby colitis was induced in Wistar rats by feeding them 5 % dextran sulfate sodium (DSS) in drinking water for one week. STW 5 and sulfasalazine (as a reference standard) were administered orally daily for 1 week before colitis induction and continued during DSS feeding. The animals were then sacrificed, and the severity of colitis was evaluated macroscopically and microscopically. Colon samples were homogenized for determination of reduced glutathione, tumor necrosis factor-a, and cytokineinduced neutrophil chemoattractant-3 as well as myeloperoxidase, glutathione peroxidase, and superoxide dismutase. In addition, colon segments were suspended in an organ bath to test their reactivity towards carbachol, KCl, and trypsin. Results STW 5 and sulfasalazine were both effective in preventing the shortening of colon length and the increase in both colon mass index and total histology score as well as the changes in biochemical parameters measured except changes in dismutase activity. DSS-induced colitis led to marked depression in colonic responsiveness to the agents tested ex vivo, an effect which was normalized by both drugs. Conclusions The findings point to a potential usefulness of STW 5 in the clinical setting of ulcerative colitis. © The Author(s) 2012.

Although a lot of herbal medicinal products are successfully used in children since centuries, the existing documentation of their clinical application does not allways fulfill the increasing regulatory requirements. Non interventional studies may be helpful in such cases. Retrospective studies are an option making the knowledge accessible contained in the physicians patient files. Advantages are their short duration and the possibility to conduct them also in case, that regulatory limitations have already taken effect, because already existing data are used. Limitations are, however, that these studies may be conducted only in products used to a significant extent or that the quality of the available patient documentations may be limited. In these points observational studies have advantages, as the data quality can be influenced prospectively by appropriate case report forms and by monitoring. Limitations are the possibly longer duration of conduct, especially in products of seasonal use, e.g. products used in common cold. Altogether, both types of studies are an ethically valid and effective tool for the systematic collection of scientific knowledge of regulatory relevance. This is confirmed by examples from two important areas of paediatric use, i.e. gastrointestinal diseases and cough/common cold.

Bonaterra G.A.,University of Marburg | Kelber O.,Steigerwald Arzneimittelwerk GmbH | Weiser D.,Steigerwald Arzneimittelwerk GmbH | Kinscherf R.,University of Marburg
Phytomedicine | Year: 2013

Introduction: Several conventional pharmaceuticals like non-steroidal anti-inflammatory drugs (NSAIDS) or selective cyclooxygenase-2 (COX-2) inhibitors have been demonstrated to exert anti-proliferative effects and to induce apoptosis in a variety of cell lines, e.g. colon, stomach, or prostate cancer cells. STW 5 (Iberogast®), a combination of nine plant extracts, is widely used in the treatment of gastrointestinal disorders, including functional dyspepsia and irritable bowel syndrome for which the involvement of an inflammatory etiology is discussed. To investigate the possible anti-proliferative effects, STW 5 and its components have been tested by using the colon-carcinoma cell line HT-29. The analyses have been performed in comparison to acetylsalicylic acid (ASA) and diclofenac (Diclo), which are well-known to reduce colon carcinoma risk. Results: STW 5 showed significant anti-proliferative and pro-apoptotic effects on HT-29 cancer cells, similar to NSAIDs under test. However, using the LDH assay, STW 5 revealed significantly lower cytotoxicity than Diclo at same concentrations. In contrast to NSAIDs, STW 5 induced COX-1/COX-2, caspase-3 and Bax mRNA expressions in HT-29 and blocked LPS mediated translocation of the NF-κB p65 from the cytoplasm into the nucleus in PMA-differentiated THP-1 macrophages. These effects might be relevant, e.g. for prevention of undesirable side effects like gastric erosions. Conclusion: Our data suggest that the pro-apoptotic effect of STW 5 on HT-29 cells is involving multiple targets and is possibly due to an activation of the caspase cascade via mitochondrial destabilization. Active concentrations of STW 5 are, in relation to therapeutic doses, comparable to those of ASA and Diclo, suggesting a similar favorable effect on colon carcinoma risk. © 2013 Elsevier GmbH. All rights reserved.

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