Institute of Pharmacy and Molecular Biotechnology

Heidelberg, Germany

Institute of Pharmacy and Molecular Biotechnology

Heidelberg, Germany
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Riyahi S.,Ferdowsi University of Mashhad | Riyahi S.,Evolutionary Ecology Associate Research Unit CSIC | Hammer O.,University of Oslo | Arbabi T.,Institute of Pharmacy and Molecular Biotechnology | And 4 more authors.
BMC Evolutionary Biology | Year: 2013

Background: The granivorous house sparrow Passer domesticus is thought to have developed its commensal relationship with humans with the rise of agriculture in the Middle East some 10,000 years ago, and to have expanded with the spread of agriculture in Eurasia during the last few thousand years. One subspecies, P. d. bactrianus, residing in Central Asia, has apparently maintained the ancestral ecology, however. This subspecies is not associated with human settlements; it is migratory and lives in natural grass- and wetland habitats feeding on wild grass seeds. It is well documented that the agricultural revolution was associated with an increase in grain size and changes in seed structure in cultivated cereals, the preferred food source of commensal house sparrow. Accordingly, we hypothesize that correlated changes may have occurred in beak and skull morphology as adaptive responses to the change in diet. Here, we test this hypothesis by comparing the skull shapes of 101 house sparrows from Iran, belonging to five different subspecies, including the non-commensal P. d. bactrianus, using geometric morphometrics. Results: The various commensal house sparrow subspecies share subtle but consistent skeletal features that differ significantly from those of the non-commensal P. d. bactrianus. Although there is a marked overall size allometry in the data set, the shape difference between the ecologically differentiated sparrows cannot be explained by differences in size alone. Relative to the size allometry commensal house sparrows exhibit a skull shape consistent with accelerated development (heterochrony), resulting in a more robust facial cranium and a larger, more pointed beak. Conclusion: The difference in skull shape and robustness of the beak between commensal and non-commensal house sparrows is consistent with adaptations to process the larger and rachis encapsulated seeds of domesticated cereals among human associated populations. © 2013 Riyahi et al.; licensee BioMed Central Ltd.


Husch J.,Central Laboratory of German Pharmacists | Gerbeth K.,Central Laboratory of German Pharmacists | Fricker G.,Institute of Pharmacy and Molecular Biotechnology | Setzer C.,Phospholipid Research Center | And 5 more authors.
Journal of Natural Products | Year: 2012

Boswellia serrata gum resin extracts are used widely for the treatment of inflammatory diseases. However, very low concentrations in the plasma and brain were observed for the boswellic acids (1-6, the active constituents of B. serrata). The present study investigated the effect of phospholipids alone and in combination with common co-surfactants (e.g., Tween 80, vitamin E-TPGS, pluronic f127) on the solubility of 1-6 in physiologically relevant media and on the permeability in the Caco-2 cell model. Because of the high lipophilicity of 1-6, the permeability experiments were adapted to physiological conditions using modified fasted state simulated intestinal fluid as apical (donor) medium and 4% bovine serum albumin in the basolateral (receiver) compartment. A formulation composed of extract/phospholipid/pluronic f127 (1:1:1 w/w/w) increased the solubility of 1-6 up to 54 times compared with the nonformulated extract and exhibited the highest mass net flux in the permeability tests. The oral administration of this formulation to rats (240 mg/kg) resulted in 26 and 14 times higher plasma levels for 11-keto-μ-boswellic acid (1) and acetyl-11-keto-μ-boswellic acid (2), respectively. In the brain, five times higher levels for 2 compared to the nonformulated extract were determined 8 h after oral administration. © 2012 The American Chemical Society and American Society of Pharmacognosy.


Fricker G.,Phospholipid Research Center | Fricker G.,University of Heidelberg | Fricker G.,Institute of Pharmacy and Molecular Biotechnology | Kromp T.,Phospholipid GmbH | And 16 more authors.
Pharmaceutical Research | Year: 2010

Phospholipids become increasingly important as formulation excipients and as active ingredients per se. The present article summarizes particular features of commonly used phospholipids and their application spectrum within oral drug formulation and elucidates current strategies to improve bioavailability and disposition of orally administered drugs. Advantages of phospholipids formulations not only comprise enhanced bioavailability of drugs with low aqueous solubility or low membrane penetration potential, but also improvement or alteration of uptake and release of drugs, protection of sensitive active agents from degradation in the gastrointestinal tract, reduction of gastrointestinal side effects of non-steroidal anti-inflammatory drugs and even masking of bitter taste of orally applied drugs. Technological strategies to achieve these effects are highly diverse and offer various possibilities of liquid, semi-liquid and solid lipid-based formulations for drug delivery optimization. © 2010 Springer Science+Business Media, LLC.


Walstab J.,University of Heidelberg | Wohlfarth C.,University of Heidelberg | Hovius R.,Ecole Polytechnique Federale de Lausanne | Schmitteckert S.,University of Heidelberg | And 5 more authors.
Neurogastroenterology and Motility | Year: 2014

Background: Impaired 5-HT3 receptor function is likely involved in the pathogenesis of functional gastrointestinal disorders (FGID) and 5-HT3 receptor antagonists are effective treatments for chemotherapy-induced nausea and vomiting (CINV) and irritable bowel syndrome (IBS). The monoterpene alcohol menthol and the aporphine alkaloid boldine combat symptoms of gastrointestinal diseases; both interact with other members of the Cys-loop ligand-gated ion channel family and may therefore also act on 5-HT3 receptors. Methods: The impact of boldine and menthol on human recombinant homomeric 5-HT3A- and heteromeric 5-HT3AB receptors in HEK293 cells was determined by radioligand binding, a luminescence-based Ca2+ assay, and a membrane potential assay. 5-HT3 protein and mRNA expression was assessed in human colon tissue. Key Results: Boldine and menthol inhibited the 5-HT-induced activation of 5-HT3 receptors in the low and middle micromolar range, respectively. Boldine was a competitive antagonist of both receptors being 6.5- to 10-fold more potent at 5-HT3A- vs 5-HT3AB receptors. Menthol non-competitively and stereoselectively inhibited both receptors: In contrast to (+)-menthol, (-)-menthol was significantly more potent toward 5-HT3A- vs 5-HT3AB receptors. We show co-expression of 5-HT3A and 5-HT3B subunits in the human gut epithelium, the lamina propria, the myenteric plexus, and the muscular cell layer. Conclusions & Inferences: The demonstrated 5-HT3 inhibitory effects may be relevant for boldine's and menthol's alleviating properties on FGID and may encourage clinical studies with the compounds or the plant extracts for CINV and IBS treatment. The found receptor-discriminative properties make boldine and (-)-menthol to potentially useful tools for analyzing structural differences between these receptor subtypes. © 2014 John Wiley & Sons Ltd.


Zu Y.,Northeast Forestry University | Fu Y.,Northeast Forestry University | Wang W.,Northeast Forestry University | Wu N.,Northeast Forestry University | And 6 more authors.
Forschende Komplementarmedizin | Year: 2010

Introduction: Aqueous and ethanolic extracts of Cajanus cajan (Fabaceae) were examined in vitro for their antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). Materials and Methods: The antiviral activity was determined using a plaque reduction assay. The cytotoxic concentration (CC50) as well as the inhibitory concentration (IC50) of the extracts was determined from dose-response curves. Results: All extracts tested revealed a high antiviral activity against cell-free HSV-1 and HSV-2. The most active one was the Cajanus ethanol extract with IC50 values of 0.022 μg/ml for HSV-1 and 0.1 μg/ml for HSV-2. In order to identify the mode of antiviral action, the extracts were added to the host cells or viruses at different stages of infection. HSV-1 and HSV-2 were considerably inactivated when the viruses were pretreated with the extracts for 1 h prior to cell infection. At maximum non-cytotoxic concentrations of the extracts, plaque formation was significantly reduced by 95-99% for HSV-1 and HSV-2. In a time-dependent assay with cell-free HSV-1 over a period of 2 h, a clearly time-dependent effect was demonstrated whereby the Cajanus ethanol extract revealed a much higher activity than the Cajanus aqueous one. Conclusion: The results obtained indicate that the extracts affect HSV before cell adsorption, but have no effect on the intracellular virus replication. According to our findings, a thera-peutic application of Cajanus ethanolic extracts containing crème or ointment as antiviral agent in recurrent HSV in-fection appears to be promising. © 2010 S. Karger GmbH, Freiburg.


Fischer M.,University of Cologne | Bauer T.,Institute of Pharmacy and Molecular Biotechnology | Bauer T.,German Cancer Research Center | Oberthur A.,University of Cologne | And 11 more authors.
Oncogene | Year: 2010

Imbalances in chromosome 11q occur in approximately 30% of primary neuroblastoma and are associated with poor outcome. It has been suggested that 11q loss constitutes a distinct clinico-genetic neuroblastoma subgroup by affecting expression levels of corresponding genes. This study analysed the relationship of 11q loss, clinical phenotype and global transcriptomic profiles in four clinico-genetic subgroups (11q alteration/favourable outcome, n7; 11q alteration/unfavourable outcome, n14; no 11q alteration/favourable outcome, n81; no 11q alteration/unfavourable outcome, n8; tumours with MYCN amplification and/or 1p loss were excluded). Unsupervised and supervised comparisons of gene expression profiles consistently showed significantly different mRNA patterns between favourable and unfavourable neuroblastomas, both in the subgroups with and without 11q loss. In contrast, favourable tumours with and without 11q loss showed highly similar transcriptomic profiles. Disproportionate downregulation of 11q genes was observed only in unfavourable tumours with 11q loss. The diverging molecular profiles were neither caused by considerable differences in the size of the deleted regions nor by differential methylation patterns of 11q genes. Together, this study shows that neuroblastoma with 11q loss comprises two biological subgroups that differ both in their clinical phenotype and gene expression patterns, indicating that 11q loss is not a primary determinant of neuroblastoma tumour behaviour. © 2010 Macmillan Publishers Limited. All rights reserved.


Braun M.,Institute of Pharmacy and Molecular Biotechnology | Buyer R.,Elisabeth von Thadden Gymnasium secondary school | Randler C.,University of Education, Heidelberg
International Journal of Environmental and Science Education | Year: 2010

"Non-native organisms are a major threat to biodiversity". This statement is often made by biologists, but general conclusions cannot be drawn easily because of contradictory evidence. To introduce pupils aged 11-14 years to this topic, we employed an educational program dealing with non-native animals in Central Europe. The pupils took part in a lesson giving general information about the topic, followed by a species identification quiz. Attitude, emotions and state of knowledge of each pupil were surveyed throughout the program using standardized questionnaires (pre-/post- and follow up tests). One week after the first lesson, a field trip followed, focusing on one out of two non-native bird species in the city of Heidelberg, Baden-Württemberg, Germany. The first species was the Ring-necked Parakeet (Psittacula krameri) from the Indian subcontinent, and the second species was the East Asian Swan goose (Anser cygnoides). Life history information was delivered through a teacher and own observations during the excursions and after four weeks, the newly gained knowledge was tested in a third lesson. The "goose group" scored higher in goose-related questions, whereas the "parakeet-group" scored higher in their topic. The most impressive aspect of the whole program was, that the pupils rated the field trip per se as highest, and secondly, learning about unfamiliar species. Interestingly, the general attitude towards non-native species did not change as a result of this educational intervention. © 2010 IJESE.


Li J.,Northeast Forestry University | Zu Y.-G.,Northeast Forestry University | Fu Y.-J.,Northeast Forestry University | Yang Y.-C.,Northeast Forestry University | And 3 more authors.
Innovative Food Science and Emerging Technologies | Year: 2010

Microwave-assisted extraction (MAE) of triterpene saponins from defatted residue of yellow horn (Xanthoceras sorbifolia Bunge.) kernel was optimized in this study. Compared with the conventional extraction methods ultrasonic-assisted extraction (UAE) and heat reflux extraction (HRE), MAE possessed higher efficiency for the extraction of triterpene saponins. The MAE conditions including extraction temperature, extraction duration, irradiation power, ethanol concentration, ratio of solvent to material and extraction cycles were studied and optimized. The optimum extraction parameters were as follows: 51 °C, 7 min, 900 W, 32 ml/g, 42% (v/v) ethanol and 3 cycles. Under the above conditions, the highest extraction yield of triterpene saponins reached 11.62 ± 0.37% of defatted kernel, which was much higher than those of conventional extraction methods. In addition, MAE extract of triterpene saponins exhibited substantial free radical-scavenging activity with an IC50 value of 0.782 mg/ml. Industrial relevance: Large amounts of defatted kernels of yellow horn are discarded after oil extraction in biodiesel production. It is not only an environmental pollution but also a waste of bioresource. In fact, the residue still has potential for bioactive and medicinal use. Therefore, this study focused on the utilization of defatted kernels of yellow horn by optimizing MAE and evaluation of the antioxidant activity of the resulting extract. MAE provided a better way to deal with defatted kernels of yellow horn as a utilization of waste material of the bioactive resource in food and pharmaceutical industry. © 2010 Elsevier Ltd.


Jahne E.A.,University of Basel | Eigenmann D.E.,University of Basel | Culot M.,University of Lille Nord de France | Cecchelli R.,University of Lille Nord de France | And 7 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2014

The compound (E,Z)-3-(4-hydroxy-3,5-dimethoxybenzylidene)indolin-2-one (indolinone) was identified from lipophilic woad extracts (Isatis tinctoria L., Brassicaceae) as a compound possessing potent histamine release inhibitory and anti-inflammatory properties [1]. To further evaluate the potential of indolinone in terms of crossing the blood-brain barrier (BBB), we screened the compound in several in vitro cell-based human and animal BBB models. Therefore, we developed a quantitative LC-MS/MS method for the compound in modified Ringer HEPES buffer (RHB) and validated it according to FDA and EMA guidelines [2,3]. The calibration curve of indolinone in the range between 30.0 and 3000. ng/ml was quadratic, and the limit of quantification was 30.0. ng/ml. Dilution of samples up to 100-fold did not affect precision and accuracy. The carry-over was within acceptance criteria. Indolinone proved to be stable in RHB for 3. h at room temperature (RT), and for three successive freeze/thaw cycles. The processed samples could be stored in the autosampler at 10. °C for at least 28. h. Moreover, indolinone was stable for at least 16 days in RHB when stored below -65. °C. This validation study demonstrates that our method is specific, selective, precise, accurate, and capable to produce reliable results. In the immortalized human BBB mono-culture model, the apparent permeability coefficient from apical to basolateral (Papp A→B), and the Papp from basolateral to apical (Papp B→A) were 19.2±0.485×10-6cm/s and 21.7±0.326×10-6cm/s, respectively. For the primary rat/bovine BBB co-culture model a Papp A→B of 27.1±1.67×10-6cm/s was determined. In the primary rat BBB triple co-culture model, the Papp A→B and the Papp B→A were 56.2±3.63×10-6cm/s and 34.6±1.41×10-6cm/s, respectively. The data obtained with the different models showed good correlation and were indicative of a high BBB permeation potential of indolinone confirmed by in silico prediction calculations. P-glycoprotein (P-gp) interaction for indolinone was studied with the aid of a calcein-AM uptake assay, and by calculation of the efflux ratio (ER) from the bidirectional permeability assays. For both bidirectional BBB models an ER below 2 was calculated, indicating that no active mediated transport mechanism is involved for indolinone. In porcine brain capillary endothelial cells (PBCECs), the calcein-AM uptake assay demonstrated that indolinone is neither a P-gp substrate nor a P-gp inhibitor and is accumulated into cells at high extent. © 2014 Elsevier B.V.


PubMed | University of Lille Nord de France, University of Basel, Hungarian Academy of Sciences and Institute of Pharmacy and Molecular Biotechnology
Type: | Journal: Journal of pharmaceutical and biomedical analysis | Year: 2014

The compound (E,Z)-3-(4-hydroxy-3,5-dimethoxybenzylidene)indolin-2-one (indolinone) was identified from lipophilic woad extracts (Isatis tinctoria L., Brassicaceae) as a compound possessing potent histamine release inhibitory and anti-inflammatory properties [1]. To further evaluate the potential of indolinone in terms of crossing the blood-brain barrier (BBB), we screened the compound in several in vitro cell-based human and animal BBB models. Therefore, we developed a quantitative LC-MS/MS method for the compound in modified Ringer HEPES buffer (RHB) and validated it according to FDA and EMA guidelines [2,3]. The calibration curve of indolinone in the range between 30.0 and 3000ng/ml was quadratic, and the limit of quantification was 30.0ng/ml. Dilution of samples up to 100-fold did not affect precision and accuracy. The carry-over was within acceptance criteria. Indolinone proved to be stable in RHB for 3h at room temperature (RT), and for three successive freeze/thaw cycles. The processed samples could be stored in the autosampler at 10C for at least 28h. Moreover, indolinone was stable for at least 16 days in RHB when stored below -65C. This validation study demonstrates that our method is specific, selective, precise, accurate, and capable to produce reliable results. In the immortalized human BBB mono-culture model, the apparent permeability coefficient from apical to basolateral (PappAB), and the Papp from basolateral to apical (PappBA) were 19.20.48510(-6)cm/s and 21.70.32610(-6)cm/s, respectively. For the primary rat/bovine BBB co-culture model a PappAB of 27.11.6710(-6)cm/s was determined. In the primary rat BBB triple co-culture model, the PappAB and the PappBA were 56.23.6310(-6)cm/s and 34.61.4110(-6)cm/s, respectively. The data obtained with the different models showed good correlation and were indicative of a high BBB permeation potential of indolinone confirmed by in silico prediction calculations. P-glycoprotein (P-gp) interaction for indolinone was studied with the aid of a calcein-AM uptake assay, and by calculation of the efflux ratio (ER) from the bidirectional permeability assays. For both bidirectional BBB models an ER below 2 was calculated, indicating that no active mediated transport mechanism is involved for indolinone. In porcine brain capillary endothelial cells (PBCECs), the calcein-AM uptake assay demonstrated that indolinone is neither a P-gp substrate nor a P-gp inhibitor and is accumulated into cells at high extent.

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