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Proceedings of the the 4th Young Researcher Meeting, Münster, March 13-14, 2015

A special issue of Molecules (ISSN 1420-3049).

Deadline for manuscript submissions: closed (30 June 2015) | Viewed by 69993

Special Issue Editor

Prof. Dr. Thomas J. Schmidt

E-Mail Website
Guest Editor
Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Corrensstrasse 48, D-48149 Münster, Germany
Interests: natural products; anti-parasitic activity; anti-cancer activity; structure elucidation; spectroscopy; computer-aided structure-activity relationship studies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The Fourth Young Researcher Meeting in the field of Natural Products and Phytotherapy, titled “Phytotherapeutics in current research – Phytochemistry, pharmacology and clinical applications”, organized by colleagues at the Universities of Münster and Leipzig, Germany, was held in Münster on March 13 and 14, 2015. Since the first event in 2007, it has always been a main aim of these meetings to bring together young scientists, mostly doctorate students, working on the many diverse aspects representing the interesting field of pharmaceutical and biomedical science, thereby fostering inspiring discussions and exchange of ideas and views. This fourth meeting, bringing together 43 participants and comprising oral and poster presentations by 28 young scientists, has once again shown that the idea to “incubate” the youngsters in a conducive environment and atmosphere always leads to fruitful and very exciting results.

It is a great pleasure to announce that the MDPI journal, Molecules, has decided to support this activity by allocating space for a Special Issue of featured papers, allowing young scientists to publish the interesting and highly valuable results presented during the meeting, free of processing charge, based entirely on scientific merit. The work published here has –during the meeting – undergone pre-selection by a jury consisting of the conference organizers, namely, Prof. Dr. Martina Düfer (University of Münster), Prof. Dr. Karen Nieber  (University of Leipzig), Prof. Dr. Andreas Hensel (University of Münster), and myself, before invitations to submit were issued. Then, of course, each of these papers had to pass the rigorous regular peer-reviewing process of Molecules.

It is our pleasure as organizers to see the fascinating work presented during the meeting manifested here in a series of high-quality publications, showing the diversity and timeliness of this exciting field of research. We sincerely thank all those who found the time to present their results at the meeting and to submit their work to this unique Special Issue of Molecules.

Thomas J. Schmidt
Guest Editor

Proceedings of the the 4th Young Researcher Meeting, Münster, March 13-14, 2015.jpg
4th YRM, Münster, March 13-14, 2015

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed Open Access monthly journal published by MDPI.

Keywords

  • natural product
  • phytotherapy
  • phytochemistry
  • phytopharmacology

Published Papers (9 papers)

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Research

1302 KiB  
Article
Lupanine Improves Glucose Homeostasis by Influencing KATP Channels and Insulin Gene Expression
by Mats Wiedemann, Carmen M. Gurrola-Díaz, Belinda Vargas-Guerrero, Michael Wink, Pedro M. García-López and Martina Düfer
Molecules 2015, 20(10), 19085-19100; https://doi.org/10.3390/molecules201019085 - 20 Oct 2015
Cited by 31 | Viewed by 6579
Abstract
The glucose-lowering effects of lupin seeds involve the combined action of several components. The present study investigates the influence of one of the main quinolizidine alkaloids, lupanine, on pancreatic beta cells and in an animal model of type-2 diabetes mellitus. In vitro studies [...] Read more.
The glucose-lowering effects of lupin seeds involve the combined action of several components. The present study investigates the influence of one of the main quinolizidine alkaloids, lupanine, on pancreatic beta cells and in an animal model of type-2 diabetes mellitus. In vitro studies were performed with insulin-secreting INS-1E cells or islets of C57BL/6 mice. In the in vivo experiments, hyperglycemia was induced in rats by injecting streptozotocin (65 mg/kg body weight). In the presence of 15 mmol/L glucose, insulin secretion was significantly elevated by 0.5 mmol/L lupanine, whereas the alkaloid did not stimulate insulin release with lower glucose concentrations. In islets treated with l-arginine, the potentiating effect of lupanine already occurred at 8 mmol/L glucose. Lupanine increased the expression of the Ins-1 gene. The potentiating effect on secretion was correlated to membrane depolarization and an increase in the frequency of Ca2+ action potentials. Determination of the current through ATP-dependent K+ channels (KATP channels) revealed that lupanine directly inhibited the channel. The effect was dose-dependent but, even with a high lupanine concentration of 1 mmol/L or after a prolonged exposure time (12 h), the KATP channel block was incomplete. Oral administration of lupanine did not induce hypoglycemia. By contrast, lupanine improved glycemic control in response to an oral glucose tolerance test in streptozotocin-diabetic rats. In summary, lupanine acts as a positive modulator of insulin release obviously without a risk for hypoglycemic episodes. Full article
(This article belongs to the Special Issue Proceedings of the the 4th Young Researcher Meeting, Münster, March 13-14, 2015)
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2032 KiB  
Article
Acetylated Rhamnogalacturonans from Immature Fruits of Abelmoschus esculentus Inhibit the Adhesion of Helicobacter pylori to Human Gastric Cells by Interaction with Outer Membrane Proteins
by Christian Thöle, Simone Brandt, Niyaz Ahmed and Andreas Hensel
Molecules 2015, 20(9), 16770-16787; https://doi.org/10.3390/molecules200916770 - 15 Sep 2015
Cited by 29 | Viewed by 7764
Abstract
Polysaccharide containing extracts from immature fruits of okra (Abelmoschus esculentus) are known to exhibit antiadhesive effects against bacterial adhesion of Helicobacter pylori (H. pylori) to stomach tissue. The present study investigates structural and functional features of polymers responsible for [...] Read more.
Polysaccharide containing extracts from immature fruits of okra (Abelmoschus esculentus) are known to exhibit antiadhesive effects against bacterial adhesion of Helicobacter pylori (H. pylori) to stomach tissue. The present study investigates structural and functional features of polymers responsible for this inhibition of bacterial attachment to host cells. Ammonium sulfate precipitation of an aqueous extract yielded two fractions at 60% and 90% saturation with significant antiadhesive effects against H. pylori, strain J99, (FE60% 68% ± 15%; FE90% 75% ± 11% inhibition rates) after preincubation of the bacteria at 1 mg/mL. Sequential extraction of okra fruits yielded hot buffer soluble solids (HBSS) with dose dependent antiadhesive effects against strain J99 and three clinical isolates. Preincubation of H. pylori with HBSS (1 mg/mL) led to reduced binding to 3ʹ-sialyl lactose, sialylated Lea and Lex. A reduction of bacterial binding to ligands complementary to BabA and SabA was observed when bacteria were pretreated with FE90%. Structural analysis of the antiadhesive polysaccharides (molecular weight, monomer composition, linkage analysis, stereochemistry, and acetylation) indicated the presence of acetylated rhamnogalacturonan-I polymers, decorated with short galactose side chains. Deacetylation of HBSS and FE90% resulted in loss of the antiadhesive activity, indicating esterification being a prerequisite for antiadhesive activity. Full article
(This article belongs to the Special Issue Proceedings of the the 4th Young Researcher Meeting, Münster, March 13-14, 2015)
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1689 KiB  
Article
In Silico Identification and in Vitro Activity of Novel Natural Inhibitors of Trypanosoma brucei Glyceraldehyde-3-phosphate-dehydrogenase
by Fabian C. Herrmann, Mairin Lenz, Joachim Jose, Marcel Kaiser, Reto Brun and Thomas J. Schmidt
Molecules 2015, 20(9), 16154-16169; https://doi.org/10.3390/molecules200916154 - 03 Sep 2015
Cited by 21 | Viewed by 5856
Abstract
As part of our ongoing efforts to identify natural products with activity against pathogens causing neglected tropical diseases, we are currently performing an extensive screening of natural product (NP) databases against a multitude of protozoan parasite proteins. Within this project, we screened a [...] Read more.
As part of our ongoing efforts to identify natural products with activity against pathogens causing neglected tropical diseases, we are currently performing an extensive screening of natural product (NP) databases against a multitude of protozoan parasite proteins. Within this project, we screened a database of NPs from a commercial supplier, AnalytiCon Discovery (Potsdam, Germany), against Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH), a glycolytic enzyme whose inhibition deprives the parasite of energy supply. NPs acting as potential inhibitors of the mentioned enzyme were identified using a pharmacophore-based virtual screening and subsequent docking of the identified hits into the active site of interest. In a set of 700 structures chosen for the screening, 13 (1.9%) were predicted to possess significant affinity towards the enzyme and were therefore tested in an in vitro enzyme assay using recombinant TbGAPDH. Nine of these in silico hits (69%) showed significant inhibitory activity at 50 µM, of which two geranylated benzophenone derivatives proved to be particularly active with IC50 values below 10 µM. These compounds also showed moderate in vitro activity against T. brucei rhodesiense and may thus represent interesting starting points for further optimization. Full article
(This article belongs to the Special Issue Proceedings of the the 4th Young Researcher Meeting, Münster, March 13-14, 2015)
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2422 KiB  
Article
Autodisplay of Human Hyaluronidase Hyal-1 on Escherichia coli and Identification of Plant-Derived Enzyme Inhibitors
by Zoya Orlando, Isabelle Lengers, Matthias F. Melzig, Armin Buschauer, Andreas Hensel and Joachim Jose
Molecules 2015, 20(9), 15449-15468; https://doi.org/10.3390/molecules200915449 - 26 Aug 2015
Cited by 14 | Viewed by 7629
Abstract
Hyaluronan (HA) is the main component of the extracellular matrix (ECM). Depending on its chain size, it is generally accepted to exert diverse effects. High molecular weight HA is anti-angiogenic, immunosuppressive and anti-inflammatory, while lower fragments are angiogenic and inflammatory. Human hyaluronidase Hyal-1 [...] Read more.
Hyaluronan (HA) is the main component of the extracellular matrix (ECM). Depending on its chain size, it is generally accepted to exert diverse effects. High molecular weight HA is anti-angiogenic, immunosuppressive and anti-inflammatory, while lower fragments are angiogenic and inflammatory. Human hyaluronidase Hyal-1 (Hyal-1) is one of the main enzymes in the metabolism of HA. This makes Hyal-1 an interesting target. Not only for functional and mechanistic studies, but also for drug development. In this work, Hyal-1 was expressed on the surface of E. coli, by applying Autodisplay, to overcome formation of inactive “inclusion bodies”. With the cells displaying Hyal-1 an activity assay was performed using “stains-all” dye. Subsequently, the inhibitory effects of four saponins and 14 plant extracts on the activity of surface displayed Hyal-1 were evaluated. The determined IC50 values were 177 µM for glycyrrhizic acid, 108 µM for gypsophila saponin 2, 371 µM for SA1657 and 296 µM for SA1641. Malvae sylvestris flos, Equiseti herba and Ononidis radix extracts showed IC50 values between 1.4 and 1.7 mg/mL. In summary, Autodisplay enabled the expression of functional human target protein Hyal-1 in E. coli and facilitated an accelerated testing of potential inhibitors. Full article
(This article belongs to the Special Issue Proceedings of the the 4th Young Researcher Meeting, Münster, March 13-14, 2015)
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476 KiB  
Article
Inhibition of Cytosolic Phospholipase A2α (cPLA2α) by Medicinal Plants in Relation to Their Phenolic Content
by Eva Arnold, Thorsten Benz, Cornelia Zapp and Michael Wink
Molecules 2015, 20(8), 15033-15048; https://doi.org/10.3390/molecules200815033 - 17 Aug 2015
Cited by 13 | Viewed by 11613
Abstract
The cytosolic phospholipase A2α(cPLA2α) is one of the potential targets for anti-inflammatory drugs, since this enzyme plays a key role in the inflammation processes seen in health disorders, like asthma, allergic reactions, arthritis and neuronal diseases. In this study, [...] Read more.
The cytosolic phospholipase A2α(cPLA2α) is one of the potential targets for anti-inflammatory drugs, since this enzyme plays a key role in the inflammation processes seen in health disorders, like asthma, allergic reactions, arthritis and neuronal diseases. In this study, cPLA2α inhibition by 43 methanol extracts from medicinal plants rich in polyphenols was determined. The eight most active extracts were derived from Ribes nigrum (IC50 of 27.7 μg/mL), Ononis spinosa (IC50 of 39.4 μg/mL), Urtica dioica (IC50 of 44.32 μg/mL), Betula sp. (IC50 of 58.02 μg/mL), Sanguisorba officinalis (IC50 of 76.25 μg/mL), Orthosiphon stamineus (IC50 of 78.83 μg/mL), Petasites hybridus (IC50 of 81.02 μg/mL) and Tussilago farfara (IC50 of 123.28 μg/mL). Additionally, the antioxidant activities of these extracts were determined with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and their phenolic content with the Folin–Ciocalteu reagent. Antioxidant activity showed a non-linear, positive correlation to the phenolic content, but no correlation of PLA2 inhibition with phenolic content could be established. This study provides evidence that cPLA2α may be a relevant target for anti-inflammatory agents. Full article
(This article belongs to the Special Issue Proceedings of the the 4th Young Researcher Meeting, Münster, March 13-14, 2015)
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2695 KiB  
Article
Recombinant Production of Snakin-2 (an Antimicrobial Peptide from Tomato) in E. coli and Analysis of Its Bioactivity
by Vera Herbel, Holger Schäfer and Michael Wink
Molecules 2015, 20(8), 14889-14901; https://doi.org/10.3390/molecules200814889 - 14 Aug 2015
Cited by 53 | Viewed by 7801
Abstract
Antimicrobial peptides (AMPs) represent a diverse group of biologically active molecules that are part of the innate immune systems of a variety of organisms. Their primary function consists of protecting the host organism against invading microorganisms, including pathogens. AMPs show a broad spectrum [...] Read more.
Antimicrobial peptides (AMPs) represent a diverse group of biologically active molecules that are part of the innate immune systems of a variety of organisms. Their primary function consists of protecting the host organism against invading microorganisms, including pathogens. AMPs show a broad spectrum of secondary structures, which are essential for antimicrobial activity. In this study, we produced snakin-2 (SN2), a 66-amino-acid-(aa)-long AMP from Solanum lycopersicum as a recombinant protein in E. coli. This AMP belongs to the GASA/GAST protein family and possesses a highly conserved 60-aa-long domain with six disulfide bonds in the C-terminus of the peptide. Because of the toxicity of SN2 against its producing E. coli strain, the AMP was attached to an N-terminal fusion protein (thioredoxin A), which was removed after affinity chromatography purification. The total yield of recombinant SN2 was approximately 1 mg/L. The membrane-active SN2 showed a bactericidal and fungicidal bioactivity, which can be explained by perforation of biomembranes of bacteria and fungi. Full article
(This article belongs to the Special Issue Proceedings of the the 4th Young Researcher Meeting, Münster, March 13-14, 2015)
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1530 KiB  
Article
Bioassay-Guided Fractionation of a Leaf Extract from Combretum mucronatum with Anthelmintic Activity: Oligomeric Procyanidins as the Active Principle
by Verena Spiegler, Jandirk Sendker, Frank Petereit, Eva Liebau and Andreas Hensel
Molecules 2015, 20(8), 14810-14832; https://doi.org/10.3390/molecules200814810 - 14 Aug 2015
Cited by 35 | Viewed by 7671
Abstract
Combretum mucronatum Schumach. & Thonn. is a medicinal plant widely used in West African traditional medicine for wound healing and the treatment of helminth infections. The present study aimed at a phytochemical characterization of a hydroalcoholic leaf extract of this plant and the [...] Read more.
Combretum mucronatum Schumach. & Thonn. is a medicinal plant widely used in West African traditional medicine for wound healing and the treatment of helminth infections. The present study aimed at a phytochemical characterization of a hydroalcoholic leaf extract of this plant and the identification of the anthelmintic compounds by bioassay-guided fractionation. An EtOH-H2O (1:1) extract from defatted leaves was partitioned between EtOAc and H2O. Further fractionation was performed by fast centrifugal partition chromatography, RP18-MPLC and HPLC. Epicatechin (1), oligomeric proanthocyanidins (OPC) 2 to 10 (mainly procyanidins) and flavonoids 11 to 13 were identified as main components of the extract. The hydroalcoholic extract, fractions and purified compounds were tested in vitro for their anthelmintic activity using the model nematode Caenorhabditis elegans. The bioassay-guided fractionation led to the identification of OPCs as the active compounds with a dose-dependent anthelmintic activity ranging from 1 to 1000 μM. Using OPC-clusters with a defined degree of polymerization (DP) revealed that a DP ≥ 3 is necessary for an anthelmintic activity, whereas a DP > 4 does not lead to a further increased inhibitory effect against the helminths. In summary, the findings rationalize the traditional use of C. mucronatum and provide further insight into the anthelmintic activity of condensed tannins. Full article
(This article belongs to the Special Issue Proceedings of the the 4th Young Researcher Meeting, Münster, March 13-14, 2015)
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525 KiB  
Article
Search for Antiprotozoal Activity in Herbal Medicinal Preparations; New Natural Leads against Neglected Tropical Diseases
by Núria Llurba-Montesino, Marcel Kaiser, Reto Brun and Thomas J. Schmidt
Molecules 2015, 20(8), 14118-14138; https://doi.org/10.3390/molecules200814118 - 04 Aug 2015
Cited by 34 | Viewed by 7916
Abstract
Sleeping sickness, Chagas disease, Leishmaniasis, and Malaria are infectious diseases caused by unicellular eukaryotic parasites (“protozoans”). The three first mentioned are classified as Neglected Tropical Diseases (NTDs) by the World Health Organization and together threaten more than one billion lives worldwide. Due to [...] Read more.
Sleeping sickness, Chagas disease, Leishmaniasis, and Malaria are infectious diseases caused by unicellular eukaryotic parasites (“protozoans”). The three first mentioned are classified as Neglected Tropical Diseases (NTDs) by the World Health Organization and together threaten more than one billion lives worldwide. Due to the lack of research interest and the high increase of resistance against the existing treatments, the search for effective and safe new therapies is urgently required. In view of the large tradition of natural products as sources against infectious diseases [1,2], the aim of the present study is to investigate the potential of legally approved and marketed herbal medicinal products (HMPs) as antiprotozoal agents. Fifty-eight extracts from 53 HMPs on the German market were tested by a Multiple-Target-Screening (MTS) against parasites of the genera Leishmania, Trypanosoma, and Plasmodium. Sixteen HMPs showed in vitro activity against at least one of the pathogens (IC50 < 10 µg/mL). Six extracts from preparations of Salvia, Valeriana, Hypericum, Silybum, Arnica, and Curcuma exhibited high activity (IC50 < 2.5 µg/mL). They were analytically characterized by UHPLC/ESI-QqTOF-MSMS and the activity-guided fractionation of the extracts with the aim to isolate and identify the active compounds is in progress. Full article
(This article belongs to the Special Issue Proceedings of the the 4th Young Researcher Meeting, Münster, March 13-14, 2015)
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1575 KiB  
Article
Salix daphnoides: A Screening for Oligomeric and Polymeric Proanthocyanidins
by Stefan Wiesneth, Frank Petereit and Guido Jürgenliemk
Molecules 2015, 20(8), 13764-13779; https://doi.org/10.3390/molecules200813764 - 29 Jul 2015
Cited by 16 | Viewed by 6237
Abstract
In the present study, a qualitative analysis of proanthocyanidins (PAs) from an aqueous-methanolic extract of Salix daphnoides VILL. bark is described. Procyanidin B1 (1), B2 (2), B3 (3), B4 (4), C1 (5), epicatechin-(4 [...] Read more.
In the present study, a qualitative analysis of proanthocyanidins (PAs) from an aqueous-methanolic extract of Salix daphnoides VILL. bark is described. Procyanidin B1 (1), B2 (2), B3 (3), B4 (4), C1 (5), epicatechin-(4β→8)-epicatechin-(4β→8)-catechin (6) and epicatechin-(4β→8)-epicatechin-(4β→8)-epicatechin-(4β→8)-catechin (7) have been isolated by a combination of different chromatographic separations on Sephadex® LH-20-, MCI®-, Diol-and RP-18-phases. Mass spectrometry, 1D- and 2D-NMR, circular dichroism and polarimetry were used for their structure elucidation and verification by comparison with the literature. Additionally, two fractions of very polar flavan-3-ols were compared: “regular” polymeric PAs received at the very end of the Sephadex® LH-20 chromatography showing no mobility on silica TLC and “unusual” PAs with the same RF-value but already eluting together with flavonoids in the Sephadex® LH-20 system. These “unusual” PAs were subsequently enriched by centrifugal partition chromatography (CPC). 13C-NMR, polarimetry, thiolysis, acid hydrolysis and phloroglucinol degradation were used to characterize both fractions. Differences in the composition of different flavan-3-ol units and the middle chain length were observed. Full article
(This article belongs to the Special Issue Proceedings of the the 4th Young Researcher Meeting, Münster, March 13-14, 2015)
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