60 results on '"Matthias Hamburger"'
Search Results
2. Rheum turkestanicum and R. ribes: Characterization of phenolic compounds and a LCESI-QqTOF MS based comparison with the officinal Chinese rhubarb, R. palmatum
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Leila Mohtashami, Maryam Akaberi, Jakob K. Reinhardt, Matthias Hamburger, Karel Nesměrák, Martin Štícha, Samad Nejad Ebrahimi, Mohammad Sadegh Amiri, Javad Asili, Mehrdad Iranshahi, Seyedeh Faezeh Taghizadeh, and Seyed Ahmad Emami
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Agronomy and Crop Science - Published
- 2023
3. New neo-clerodane diterpenes from Teucrium polium subsp. capitatum
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Morris Keller, Sarra Chabane, Amel Boudjelal, Ombeline Danton, Alessandro Prescimone, Matthias Hamburger, and Olivier Potterat
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Inorganic Chemistry ,Organic Chemistry ,Spectroscopy ,Analytical Chemistry - Published
- 2023
4. Chemical constituents and cytotoxic activity of Stachys pilifera Benth
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Houri Sepehri, Mahdi Moridi Farimani, Matthias Hamburger, Zeinab Mazarei, Ombeline Danton, Ladan Delphi, Marzieh Tabefam, Azadeh Khademian, and Mohammad Reza Kanani
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0106 biological sciences ,Traditional medicine ,Chemistry ,fungi ,food and beverages ,Plant Science ,01 natural sciences ,Stachys pilifera ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Phytochemical ,Breast cancer cell line ,Chemical constituents ,Cytotoxic T cell ,Cytotoxicity ,010606 plant biology & botany - Abstract
Phytochemical investigation of the n-hexane extract of Stachys pilifera Benth. aerial parts resulted in the isolation of twelve compounds. Structures were elucidated using 1D and 2D-NMR, as well as HRMS. The purified compounds identified as one new monoglyceride (1), nine flavonoids (2–10), and two steroidal compounds. The cytotoxicity effects of purified compounds were evaluated against breast cancer cell line (MCF-7) and structural-activity relationship of the flavonoids were investigated.
- Published
- 2021
5. Intestinal permeability and gut microbiota interactions of pharmacologically active compounds in valerian and St. John’s wort
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Antoine Chauveau, Andrea Treyer, Annelies Geirnaert, Lea Bircher, Angela Babst, Vanessa Fabienne Abegg, Ana Paula Simões-Wüst, Christophe Lacroix, Olivier Potterat, and Matthias Hamburger
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Pharmacology ,Short-chain fatty acids ,Hyperforin ,Hypericin ,Gut microbiota ,General Medicine ,Valerenic acid ,Caco-2 cells - Abstract
Phytomedicines such as valerian and St. John's wort are widely used for the treatment of sleeping disorders, anxiety and mild depression. They are perceived as safe alternatives to synthetic drugs, but limited information is available on the intestinal absorption and interaction with human intestinal microbiota of pharmacologically relevant constituents valerenic acid in valerian, and hyperforin and hypericin in St. John's wort. The intestinal permeability of these compounds and the antidepressant and anxiolytic drugs citalopram and diazepam was investigated in the Caco-2 cell model with bidirectional transport experiments. In addition, interaction of compounds and herbal extracts with intestinal microbiota was evaluated in artificial human gut microbiota. Microbiota-mediated metabolisation of compounds was assessed, and bacterial viability and short-chain fatty acids (SCFA) production were measured in the presence of compounds or herbal extracts. Valerenic acid and hyperforin were highly permeable in Caco-2 cell monolayers. Hypericin showed low-to-moderate permeability. An active transport process was potentially involved in the transfer of valerenic acid. Hyperforin and hypericin were mainly transported through passive transcellular diffusion. All compounds were not metabolized over 24 h in the artificial gut microbiota. Microbial SCFA production and bacterial viability was not substantially impaired nor promoted by exposure to the compounds or herbal extracts., Biomedicine & Pharmacotherapy, 162, ISSN:0753-3322, ISSN:1950-6007
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- 2023
6. A neolignan from Connarus tuberosus as an allosteric GABAA receptor modulator at the neurosteroid binding site
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Teresa Faleschini, Nova Syafni, Heidi Luise Schulte, Aleksandra Garifulina, Steffen Hering, Laila Salmen Espindola, and Matthias Hamburger
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Pharmacology ,General Medicine - Published
- 2023
7. Aryltetralin lignans from Hyptis brachiata inhibiting T lymphocyte proliferation
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Morris Keller, Moritz Winker, Amy Marisa Zimmermann-Klemd, Nino Sperisen, Mahabir P. Gupta, Pablo N. Solis, Matthias Hamburger, Olivier Potterat, and Carsten Gründemann
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Pharmacology ,General Medicine - Abstract
Increased activation and proliferation of T lymphocytes plays an essential role in the development of chronic inflammation and autoimmune diseases. Currently used immunosuppressive drugs often do not provide long-lasting relief of symptoms and show a gradual loss of efficacy over time, and are accompanied by various side effects. Therefore, novel immunosuppressive lead substances are needed. For this purpose, an in-house library consisting of 600 extracts of plants from Panama was screened for inhibition of human T lymphocyte proliferation. As one of the hits, an ethyl acetate extract from the aerial parts of Hyptis brachiata (Lamiaceae) exhibited strong inhibitory effects. Subsequent investigation resulted in the isolation of seven aryltetralin lignans, five arylnaphthalene lignans, two flavonoids, three triterpenes, and cinnamyl cinnamate. Aryltetralin lignans inhibited T lymphocyte proliferation in a concentration-dependent manner without induction of apoptosis. No relevant inhibition was observed for the arylnaphthalene lignans, flavonoids, and triterpenes. Additional cell cycle arrest investigations revealed that isolated aryltetralin lignans potently inhibited cell division in G2/M phase similarly to podophyllotoxin. Multifluorescence panel analyses of the extract also showed weak suppressive effects on the production of IL-2 and TNF-α. Therefore, preparations made out of H. brachiata could be further explored as an interesting herbal alternative in the treatment of autoimmune diseases.
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- 2023
8. Polyacetylenic caffeoyl amides from Ammodaucus leucotrichus
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Ahmed Hajib, Ombeline Danton, Morris Keller, Olivier Potterat, Khalid Bougrin, Zoubida Charrouf, and Matthias Hamburger
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Plant Science ,General Medicine ,Horticulture ,Molecular Biology ,Biochemistry - Abstract
Six undescribed polyacetylenic caffeoyl amides, five known flavones and three known lignans were obtained from the fruits of the North African traditional medicinal plant Ammodaucus leucotrichus Coss.Durieu (Apiaceae). Isolation was achieved by a combination of chromatographic methods, and structures were established by extensive 1D and 2D NMR spectroscopy, mass spectrometry, electronic circular dichroism, and by GC-MS analysis of sugar derivatives. Polyacetylenic caffeoyl amides are reported for the first time as specialized metabolites.
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- 2023
9. Anti-proliferative activity-guided isolation of clerodermic acid from Salvia nemorosa L.: Geno/cytotoxicity and hypoxia-mediated mechanism of action
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Matthias Hamburger, Maria De Mieri, Morteza Eskandani, Hossein Nazemiyeh, and Mir Babak Bahadori
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0301 basic medicine ,Magnetic Resonance Spectroscopy ,Salvia nemorosa ,Down-Regulation ,Apoptosis ,Naphthalenes ,Pharmacology ,Salvia ,Real-Time Polymerase Chain Reaction ,Toxicology ,medicine.disease_cause ,01 natural sciences ,Inhibitory Concentration 50 ,Lactones ,03 medical and health sciences ,medicine ,Humans ,Cytotoxic T cell ,MTT assay ,RNA, Messenger ,Annexin A5 ,Hypoxia ,Cytotoxicity ,Cell Proliferation ,Molecular Structure ,biology ,010405 organic chemistry ,Chemistry ,General Medicine ,Hypoxia-Inducible Factor 1, alpha Subunit ,biology.organism_classification ,0104 chemical sciences ,030104 developmental biology ,Mechanism of action ,A549 Cells ,Carcinogens ,Biological Assay ,medicine.symptom ,Genotoxicity ,Mutagens ,Food Science - Abstract
The adaptation of solid tumors to the low oxygen/nutrient environment is mediated by the pivotal transcription role of hypoxia-inducible factor-1 (HIF-1). Thus, the HIF-1 and its subunits have been considered to be hopeful anti-cancer targets. Various natural compounds were reported to persuade cell cytotoxicity through targeting and downregulation of the HIF-1. The genus Salvia is a rich source of bioactive terpenoids which show promising anti-cancer activities. Here, the identification of natural anti-proliferative compound targeting the HIF-1α expression was reported. A bioassay-guided isolation was employed for the discovery of natural anti-proliferative compounds from Salvia extracts using MTT assay against A549 cells. In this direction, clerodermic acid (CDA) as a potent cytotoxic compound was purified from Salvia nemorosa and identified using 1D and 2D NMR analysis. Results indicated that CDA has anti-proliferation activity (IC50 value of 35 μg/mL) which was confirmed by genotoxicity and apoptosis detection analyses. The quantitative qPCR analysis showed that the expression level of HIF-1 alpha was strongly inhibited in the hypoxic cells treated with CDA compared to the untreated cells tolerated hypoxia. Findings exhibited that S. nemorosa and clerodermic acid have significant potential for reducing HIF-1α expression and could be considered for further studies for cancer therapy.
- Published
- 2018
10. GABAA receptor activity modulating piperine analogs: In vitro metabolic stability, metabolite identification, CYP450 reaction phenotyping, and protein binding
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Marko D. Mihovilovic, Götz Schlotterbeck, Timm Hettich, Matthias Hamburger, Bénédicte Shevchenko, Volha Zabela, Mouhssin Oufir, Belkacem Bouaita, Fabrice Guillet, and Laurin Wimmer
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0301 basic medicine ,Chromatography ,GABAA receptor ,Metabolite ,Clinical Biochemistry ,Allosteric regulation ,Cell Biology ,General Medicine ,Metabolism ,030226 pharmacology & pharmacy ,Biochemistry ,Analytical Chemistry ,Hydroxylation ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,chemistry ,Piperine ,Binding site ,Receptor - Abstract
In a screening of natural products for allosteric modulators of GABAA receptors (γ-aminobutyric acid type A receptor), piperine was identified as a compound targeting a benzodiazepine-independent binding site. Given that piperine is also an activator of TRPV1 (transient receptor potential vanilloid type 1) receptors involved in pain signaling and thermoregulation, a series of piperine analogs were prepared in several cycles of structural optimization, with the aim of separating GABAA and TRPV1 activating properties. We here investigated the metabolism of piperine and selected analogs in view of further cycles of lead optimization. Metabolic stability of the compounds was evaluated by incubation with pooled human liver microsomes, and metabolites were analyzed by UHPLC-Q-TOF-MS. CYP450 isoenzymes involved in metabolism of compounds were identified by reaction phenotyping with Silensomes™. Unbound fraction in whole blood was determined by rapid equilibrium dialysis. Piperine was the metabolically most stable compound. Aliphatic hydroxylation, and N- and O-dealkylation were the major routes of oxidative metabolism. Piperine was exclusively metabolized by CYP1A2, whereas CYP2C9 contributed significantly in the oxidative metabolism of all analogs. Extensive binding to blood constituents was observed for all compounds.
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- 2018
11. Immunosuppressant flavonoids from Scutellaria baicalensis
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AM Klemd, N Syafni, Jakob K. Reinhardt, Matthias Hamburger, Ombeline Danton, and Carsten Gründemann
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T-Lymphocytes ,T-lymphocyte proliferation ,RM1-950 ,Immunosuppressant activity ,Lymphocyte Activation ,Plant Roots ,High-performance liquid chromatography ,Flavones ,Structure-Activity Relationship ,Immune system ,Activity profiling ,Ic50 values ,Humans ,Cells, Cultured ,Cell Proliferation ,Flavonoids ,Pharmacology ,chemistry.chemical_classification ,Molecular Structure ,Traditional medicine ,biology ,Plant Extracts ,Chemistry ,HPLC based activity profiling ,General Medicine ,biology.organism_classification ,Biochemistry ,Active time ,Scutellaria baicalensis ,Therapeutics. Pharmacology ,Immunosuppressive Agents - Abstract
Some plants used in Traditional Chinese Medicine serve as treatment for disease states where a suppression of the cellular immune response is desired. However, the compounds responsible for the immunosuppressant effects of these plants are not necessarily known. The immunosuppressant compounds in the roots of Scutellaria baicalensis, one of the most promising plants identified in a previous screening, were tracked by HPLC activity profiling and concomitant on-line spectroscopic analysis. Compounds were then isolated by preparative chromatography, and structures elucidated by spectroscopic methods. Twelve flavonoids (5–16) were identified from the active time windows, and structurally related flavones 2, 4, and 17, and flavanones 1 and 3 were isolated from adjacent fractions. All flavonoids possessed an unusual substitution pattern on the B-ring, with an absence of substituents at C-3 and C-4. Compounds 11, 13, 14, and 16 inhibited T-cell proliferation (IC50 values at 12.1–39 μM) at non-cytotoxic concentrations. The findings may support the use of S. baicalensis in disorders where a modulation of the cellular immune response is desirable.
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- 2021
12. Development of a solid-supported cysteinyl probe for the isolation of electrophiles from plant pollen extracts
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Andrea Treyer, Ombeline Danton, Matthias Hamburger, and J.T. Wang
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02 engineering and technology ,Asteraceae ,medicine.disease_cause ,Sesquiterpene ,01 natural sciences ,Analytical Chemistry ,chemistry.chemical_compound ,Nucleophile ,Liquid chromatography–mass spectrometry ,Pollen ,Hypersensitivity ,otorhinolaryngologic diseases ,medicine ,Humans ,Plant Proteins ,chemistry.chemical_classification ,biology ,Plant Extracts ,010401 analytical chemistry ,food and beverages ,Allergens ,021001 nanoscience & nanotechnology ,biology.organism_classification ,0104 chemical sciences ,chemistry ,Biochemistry ,Electrophile ,Thiol ,0210 nano-technology ,Pollen extracts - Abstract
Recent research showed that plant secondary metabolites in pollen may exacerbate the protein-mediated allergic reaction in pollen allergy. It was found that allergenic pollen from various plant families contain significant amounts of electrophiles which may covalently bind to nucleophilic groups of proteins, such as thiol moieties. Electrophiles in pollen of the Asteraceae species are typically sesquiterpene lactones, but the nature of electrophilic metabolites in allergenic pollen of other plant families is unknown. We developed a solid-supported cysteinyl probe in order to selectively extract physiologically relevant electrophiles from pollen extracts, and to enable their subsequent characterization by on-line and off-line spectroscopic analysis. The validity of this approach was evaluated with a selection of structurally different model compounds and with a spiked model extract.
- Published
- 2021
13. Dammarane-type saponins from leaves of Ziziphus spina-christi
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Frank Gafner, Alen Bozicevic, Angela Di Benedetto, Matthias Hamburger, and Maria De Mieri
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Plant Science ,Sapogenin ,Horticulture ,01 natural sciences ,Biochemistry ,High-performance liquid chromatography ,Gel permeation chromatography ,chemistry.chemical_compound ,Column chromatography ,Chromatography detector ,Organic chemistry ,Molecular Biology ,Chromatography, High Pressure Liquid ,Ziziphus spina-christi ,Chromatography ,Molecular Structure ,biology ,010405 organic chemistry ,Dammarane ,Ziziphus ,General Medicine ,Saponins ,biology.organism_classification ,Triterpenes ,0104 chemical sciences ,Plant Leaves ,010404 medicinal & biomolecular chemistry ,chemistry - Abstract
Phytochemical profiling of Ziziphus spina-christi leaves led to the characterization of 10 dammarane-type saponins and 12 phenolic compounds. Isolation was achieved by gel chromatography on Sephadex LH20, open column chromatography on silica gel, and semi-preparative HPLC with PDA and ELSD detectors. Structural characterization was performed by extensive 1D and 2D NMR, mass spectrometry, and by GC-MS of sugar derivatives. A biosynthetic pathway leading to three previously undescribed sapogenins is proposed. The saponin profiles in Z. spina-christi leaves of four different origins were compared by means of HPLC-ESIMS.
- Published
- 2017
14. Pharmacokinetics of dietary kaempferol and its metabolite 4-hydroxyphenylacetic acid in rats
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Matthias Hamburger, Chethan Sampath, Mouhssin Oufir, Fahimeh Moradi-Afrapoli, Veronika Butterweck, and Volha Zabela
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Male ,0301 basic medicine ,medicine.drug_class ,Metabolite ,Administration, Oral ,Biological Availability ,Pharmacology ,01 natural sciences ,Anxiolytic ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Pharmacokinetics ,Tandem Mass Spectrometry ,Oral administration ,Drug Discovery ,medicine ,Animals ,Distribution (pharmacology) ,Kaempferols ,Chromatography, High Pressure Liquid ,Phenylacetates ,010401 analytical chemistry ,General Medicine ,Diet ,Rats ,0104 chemical sciences ,3. Good health ,Bioavailability ,4-Hydroxyphenylacetic acid ,030104 developmental biology ,chemistry ,Injections, Intravenous ,Kaempferol ,Half-Life - Abstract
Scope Kaempferol is a major flavonoid in the human diet and in medicinal plants. The compound exerts anxiolytic activity when administered orally in mice, while no behavioural changes were observed upon intraperitoneal administration, or upon oral administration in gut sterilized animals. 4-Hydroxyphenylacetic acid (4-HPAA), which possesses anxiolytic effects when administered intraperitoneally, is a major intestinal metabolite of kaempferol. Pharmacokinetic properties of the compounds are currently not clear. Methods and results UHPLC-MS/MS methods were validated to support pharmacokinetic studies of kaempferol and 4-HPAA in rats. Non-compartmental and compartmental analyses were performed. After intravenous administration, kaempferol followed a one-compartment model, with a rapid clearance (4.40–6.44 l/h/kg) and an extremely short half-life of 2.93–3.79 min. After oral gavage it was not possible to obtain full plasma concentration–time profiles of kaempferol. Pharmacokinetics of 4-HPAA was characterized by a two-compartment model, consisting of a quick distribution phase (half-life 3.04–6.20 min) followed by a fast elimination phase (half-life 19.3–21.1 min). Conclusion Plasma exposure of kaempferol is limited by poor oral bioavailability and extensive metabolism. Both compounds are rapidly eliminated, so that effective concentrations at the site of action do not appear to be reached. At present, it is not clear how the anxiolytic-like effects reported for the compounds can be explained.
- Published
- 2016
15. Boswellia carteri extract and 3-O-acetyl-alpha-boswellic acid suppress T cell function
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Matthias Hamburger, Thanasan Nilsu, Carsten Gründemann, Amy Marisa Zimmermann-Klemd, Chiara Madlen Falanga, Jakob K. Reinhardt, Anna Morath, Roman Huber, and Wolfgang W. A. Schamel
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Interleukin 2 ,T-Lymphocytes ,T cell ,Phytochemicals ,Anti-Inflammatory Agents ,Apoptosis ,01 natural sciences ,Jurkat cells ,Cell Degranulation ,Jurkat Cells ,chemistry.chemical_compound ,Drug Discovery ,medicine ,Humans ,Boswellia ,Cytotoxicity ,Cell Proliferation ,Pharmacology ,Molecular Structure ,biology ,Plant Extracts ,010405 organic chemistry ,Degranulation ,General Medicine ,biology.organism_classification ,Triterpenes ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Cytokines ,Boswellic acid ,Cytokine secretion ,Immunosuppressive Agents ,Resins, Plant ,medicine.drug - Abstract
Resins from various Boswellia species have a long track record in different cultures as a treatment for inflammatory diseases. This study was designed to provide evidence for the anti-inflammatory capacity and medicinal use of Boswellia carteri (Burseraceae). A dichloromethane (DCM) extract of B. carteri gum resin and isolated compounds thereof were immunologically characterized. Flow cytometric-based analysis was performed to investigate the impact of B. carteri extract on proliferation, viability, and function of anti-CD3 and anti-CD28 activated human primary T cells. The secretion level of IL-2 and IFN-γ was determined by a bead array-based flow cytometric technique. HPLC-based activity profiling of the B. carteri extract identified active compounds. The impact of B. carteri extract and isolated compounds on the IL-2 transcription factor activity was addressed using specially designed Jurkat reporter cells. The extract of B. carteri suppressed the proliferation of human primary T lymphocytes in vitro in a concentration-dependent manner, without inducing cytotoxicity. Thereby, the B. carteri extract further reduced the degranulation capacity and cytokine secretion of stimulated human T cells. Transcription factor analysis showed that the immunosuppressive effects of the extract are based on specific NFAT-conditioned suppression within T cell signaling. Through HPLC-based activity profiling of the extract, 3-O-acetyl-alpha-boswellic acid was identified as the compound responsible for the NFAT-based mechanism. The recent study presents a scientific base for the immunosuppressive effects of B. carteri gum resin extract including a mode-of-action via the NFAT-conditioned suppression of T lymphocyte proliferation. The immunosuppressive effects of 3-O-acetyl-alpha-boswellic acid are depicted for the first time.
- Published
- 2020
16. Plant and natural product based homemade remedies manufactured and used by farmers of six central Swiss cantons to treat livestock
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Tinetta Bischoff, Michael Walkenhorst, Beat Meier, Christian R. Vogl, Matthias Hamburger, Franziska Klarer, and Silvia Ivemeyer
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General Veterinary ,biology ,Traditional medicine ,business.industry ,Coffea ,food and beverages ,Health and welfare ,biology.organism_classification ,01 natural sciences ,Absinthium ,030205 complementary & alternative medicine ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,03 medical and health sciences ,0302 clinical medicine ,Calendula officinalis ,Senecio ovatus ,Medicine ,Animal Science and Zoology ,Livestock ,Artemisia absinthium ,business ,Urtica dioica ,Medicinal plants - Abstract
The use of medicinal plants and other natural multicomponent remedies might be one measure to reduce the use of antibiotics in livestock. Ethnoveterinary research has the potential to identify promising natural remedies. The knowledge about remedies for livestock was collected from farmers in six central Swiss cantons, Glarus, Obwalden, Nidwalden, Schwyz, Zug and Uri. Between February and April 2013 49 interviews with 63 farmers (25 females and 38 males, aged 24–74) were conducted. We collected information on the manufacturing of 370 homemade remedies. Of these, 114 contained no plants, 26 contained a mixture of two to five plants, and 230 contained one plant species (defined as homemade single-herbal remedy report (HSHR)). These 230 HSHRs represented 68 plant species belonging to 35 different botanical families. Thirteen species were reported for the first time for ethnoveterinary use in Switzerland. Matricaria recutita, Calendula officinalis, Urtica dioica and Coffea were the most frequently used ingredients of HSHR. A total of 278 use reports (UR) were described for the 230 HSHR, (233 UR for treating cattle). Treatment of skin disorders (QD), gastrointestinal diseases and metabolic dysfunction (QA) were the most frequently mentioned uses for these remedies. Fewer uses were linked to treatments of the respiratory system (QR), the genito-urinary (QG) and musculo-skeletal systems (QM). In the categorie QA the most UR were described for Matricaria recutita, Linum usitatissimum, and Camellia sinensis. Quercus robur was mainly used to treat diarrhoea in calfs, Coffea Arabica to treat general gastrointestinal troubles, colic, abdominal pain or diarrhoea, and Arthemisia absinthium to treat general gastro-intestinal disorders, diarrhoea or lack of appetite. For four orally administered plant species (Artemisia absinthium, Avena sativa, Citrus x limon, Quercus robur) daily oral doses were determined for the first time (median: 0.03, 6.16, 0.01 and 0.58 g dry plant equivalent per kg0.75). In the category QD the most often described plant species were Calendula officinalis, Matricaria recutita, Picea abies, Sanicula europaea and Senecio ovatus. For the latter two plant species we determined for the first time an ethnoveterinary based concentration in the finished product (median: 0.13 and 0.39 g dry plant equivalent per 100 g finished product). Medicinal plants are known, and used by farmers of central Switzerland mostly for treatment of skin and gastrointestinal diseases. According to recent pharmaceutical and human clinical research several plant species documented in this ethnoveterinary study are worth to be further investigated in clinical trials with livestock.
- Published
- 2016
17. Molecular mechanisms of endocrine and metabolic disruption: An in silico study on antitrypanosomal natural products and some derivatives
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Zhenquan Hu, Matthias Hamburger, Joel Wahl, and Angelo Vedani
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0301 basic medicine ,Drug ,Protein Conformation ,In silico profiling ,In silico ,media_common.quotation_subject ,Trypanosoma brucei brucei ,Protozoan Proteins ,Computational biology ,Plasma protein binding ,Endocrine Disruptors ,Molecular Dynamics Simulation ,Biology ,Toxicology ,Risk Assessment ,01 natural sciences ,Antitrypanosomal natural products ,Structure-Activity Relationship ,03 medical and health sciences ,Cytochrome P-450 Enzyme Inhibitors ,Humans ,Structure–activity relationship ,Endocrine system ,Drug Interactions ,media_common ,Molecular Structure ,Adverse effects ,Molecular-dynamics simulations ,General Medicine ,Trypanocidal Agents ,Small molecule ,0104 chemical sciences ,VirtualToxLab ,010404 medicinal & biomolecular chemistry ,030104 developmental biology ,Biochemistry ,Energy Metabolism ,Protein Binding ,Applicability domain - Abstract
The VirtualToxLab is an in silico technology for estimating the toxic potential – endocrine and metabolic disruption, as well as aspects of carcinogenicity and cardiotoxicity – of drugs, chemicals and natural products. The technology is based on an automated protocol that simulates and quantifies the binding of small molecules towards a series of currently 16 proteins, known or suspected to trigger adverse effects. The simulations are conducted at the atomic level and explicitly allow for a mechanistic interpretation of the results (in real-time 3D/4D), thereby complying with the Setubal principles put forward in 2002 for computational approaches to toxicology. Moreover, the underlying “ab-initio” protocol is independent from any training data and makes the approach universal with respect to the applicability domain. The VirtualToxLab runs in client–server mode and is freely available to academic and non-profit organizations. As the underlying technology yields a thermodynamic estimate of the binding affinity, the associated ligand–protein complexes have been challenged by molecular-dynamics simulations to probe their kinetic stability.Human African trypanosomiasis is a neglected tropical disease caused by two subspecies of Trypanosoma brucei. The control of this parasitic infection relies on a few chemotherapeutic agents, most of which were discovered decades ago and pose many challenges including adverse side effects, poor efficacy, and the occurrence of drug resistances. Natural products, on the other hand, offer a high potential for the discovery of new drug leads due to their chemical diversity. In this in silico study, we analyze a series of 89 natural products and derivatives displaying anti-trypanosomal activity for their potential to trigger adverse effects. Our results indicate a moderate potential for a number of those compounds to bind to nuclear receptors and thereby ease the development of endocrine disregulation. A few others would seem to inhibit enzymes of the cytochrome P450 family and, hence, sustain drug–drug interactions.
- Published
- 2016
18. Tyrosinase inhibitory constituents from a polyphenol enriched fraction of rose oil distillation wastewater
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Jessica Solimine, Veronika Butterweck, Krasimir Rusanov, Jonas Wedler, Orlando Fertig, Ivan Atanassov, Matthias Hamburger, and Eliane Garo
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0301 basic medicine ,Tyrosinase ,Mixed inhibition ,Flowers ,Wastewater ,Rosa ,01 natural sciences ,law.invention ,Steam distillation ,03 medical and health sciences ,chemistry.chemical_compound ,Ellagic Acid ,law ,Drug Discovery ,Organic chemistry ,Kaempferols ,Distillation ,Pharmacology ,Chromatography ,biology ,Monophenol Monooxygenase ,Chemistry ,Polyphenols ,General Medicine ,biology.organism_classification ,6. Clean water ,0104 chemical sciences ,Rose oil ,010404 medicinal & biomolecular chemistry ,030104 developmental biology ,Polyphenol ,Quercetin ,Agaricales ,Kaempferol ,Kojic acid ,Ellagic acid - Abstract
During the water steam distillation process of rose flowers, the non-volatile phenolic compounds remain in the waste. We recently developed a strategy to separate rose oil distillation water (RODW) into a polyphenol depleted water fraction and a polyphenol enriched fraction (RF20-SP207). Bioassay-guided investigation of RF20-SP207 led to the isolation of quercetin, kaempferol and ellagic acid. Their structures were elucidated by spectroscopic analysis as well as by comparison with literature data. Tyrosinase inhibition studies were performed with RF20-SP207, fractions I-IV, and the isolated compounds of the most active fraction. RF20-SP207 strongly inhibited the enzyme with an IC50 of 0.41 μg/mL. From the tested fractions only fraction IV (IC50=5.81 μg/mL) exhibited strong anti-tyrosinase activities. Quercetin, kaempferol and ellagic acid were identified in fraction IV and inhibited mushroom tyrosinase with IC50 values of 4.2 μM, 5.5 μM and 5.2 μM, respectively, which is approximately 10 times more potent than that of the positive control kojic acid (56.1μM). The inhibition kinetics, analyzed by Lineweaver-Burk plots, indicated that RF20-SP207 and fraction IV are uncompetitive inhibitors of tyrosinase when l-tyrosine is used as a substrate. A mixed inhibition was determined for ellagic acid, and a competitive inhibition for quercetin and kaempferol. In conclusion, the recovered polyphenol fraction RF20-SP207 from RODW was found to be a potent tyrosinase inhibitor. This value-added product could be used as an active ingredient in cosmetic products related to hyperpigmentation.
- Published
- 2016
19. Metabolite profiling for caffeic acid oligomers in Satureja biflora
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Peyman Salehi, Rose Marubu, Frank Gafner, Matthias Hamburger, John Bwire Ochola, Sara E. Moghadam, Samad Nejad Ebrahimi, Wilber Lwande, and Barbara Frei Haller
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chemistry.chemical_classification ,food.ingredient ,Traditional medicine ,biology ,Rosmarinic acid ,Flavonoid ,Antimicrobial ,biology.organism_classification ,Satureja ,law.invention ,chemistry.chemical_compound ,food ,Phytochemical ,chemistry ,law ,Caffeic acid ,Organic chemistry ,Lamiaceae ,Agronomy and Crop Science ,Essential oil - Abstract
Satureja biflora, known as “lemon savory”, grows widely in Southern and Eastern parts of Africa. The plant has been used in Kenyan and Tanzanian traditional medicine as an antimicrobial, spasmolytic, diuretic, analgesic, and cicatrizing herb. Except for the composition of the essential oil no phytochemical data have been reported. Phytochemical profiling of the methanolic extract by a combination of chromatographic methods afforded nine phenolic compounds. Their structures were established by means of extensive 1D- and 2D-NMR, HRESI–MS, and electronic circular dichroism (ECD). One new and eight known natural products were isolated and identified, namely luteolin 7-O-β-d-glucuronide (1), 2″-caffeoyl-luteolin 7-O-β-d-glucuronide (2) rosmarinic acid (3), melitric acid A (4), methyl melitric acid A (5), clinopodic acid I (6), clinopodic acid K (7), clinopodic acid O (8) and clinopodic acid P (9). Quantitative analysis of compounds showed that S. biflora is a rich source of caffeic acid oligomers. Such compounds were also found in other Satureja species, but at significantly lower concentrations.
- Published
- 2015
20. Single dose pharmacokinetics of intravenous 3,4-dihydroxyphenylacetic acid and 3-hydroxyphenylacetic acid in rats
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Chethan Sampath, Mouhssin Oufir, Veronika Butterweck, Matthias Hamburger, and Volha Zabela
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Male ,3,4-Dihydroxyphenylacetic acid ,Lithium (medication) ,medicine.drug_class ,Pharmacology ,01 natural sciences ,Anxiolytic ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Pharmacokinetics ,Drug Discovery ,medicine ,Animals ,Distribution (pharmacology) ,3-hydroxyphenylacetic acid ,Phenylacetates ,010405 organic chemistry ,General Medicine ,Heparin ,3. Good health ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,nervous system ,chemistry ,3,4-Dihydroxyphenylacetic Acid ,Administration, Intravenous ,Quercetin ,medicine.drug - Abstract
3,4-Dihydroxyphenylacetic acid (DOPAC) and 3-hydroxyphenylacetic acid (3-HPAA) are intestinal metabolites of the dietary flavonoid quercetin. DOPAC reportedly showed anxiolytic activity after i.p. administration in rats. The fate of these metabolites after consumption, and the pharmacological properties of 3-HPAA in the body are largely unknown. The aim of the current study was to characterize pharmacokinetic properties of DOPAC and 3-HPAA after intravenous bolus application in rats. UHPLC-MS/MS methods for quantification of DOPAC and 3-HPAA levels in lithium heparin Sprague Dawley rat plasma were developed and validated according to international regulatory guidelines. Non-compartmental and compartmental analyses were performed. Pharmacokinetic profiles of DOPAC and 3-HPAA followed a two-compartment body model, with a fast distribution into peripheral tissues (half-lives of 3.27–5.26 min) and rapid elimination from the body (half-lives of 18.4–33.3 min).
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- 2020
21. Ethnoveterinary knowledge of farmers in bilingual regions of Switzerland – is there potential to extend veterinary options to reduce antimicrobial use?
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Maja Dal Cero, Ariane Maeschli, Silvia Ivemeyer, Christian R. Vogl, Matthias Hamburger, Doréane Mertenat, Beat Meier, and Michael Walkenhorst
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Male ,Health Knowledge, Attitudes, Practice ,Veterinary medicine ,Gastrointestinal Diseases ,Ethnobotany ,QD, dermatologicals ,QM, musculo-skeletal system ,Health and welfare ,Cattle Diseases ,Skin disease ,German ,0302 clinical medicine ,Anti-Infective Agents ,French speaking swiss region (Fribourg, Jura, Jura bernois, Neuchãchtel)) ,Drug Discovery ,Jura bernois) ,QG52, mastitis ,Middle aged ,Medicinal plants ,Language ,FNS, French native speaker ,Aged, 80 and over ,0303 health sciences ,Farmers ,Livestock disease ,biology ,MBW, Metabolic bodyweight ,Medicinal plant ,food and beverages ,QG, genito urinary system and sex hormones ,French speaking swiss regions (Fribourg ,Gastrointestinal disease ,Geography ,030220 oncology & carcinogenesis ,PSES, previous Swiss ethnoveterinary studies ,language ,Female ,Livestock ,Switzerland ,HSHR, Homemade-Single-Species Herbal Remedy Reports ,Adult ,dpe, dry plant equivalent ,QR, respiratory system ,Ethnoveterinary medicine ,CNS, central nervous system ,Skin Diseases ,630: Landwirtschaft ,Article ,Livestock diseases ,03 medical and health sciences ,Jura ,DP, dialog partners ,Health knowledge ,Animals ,Humans ,Horses ,Neuchâtel ,VAS, visual analog scale ,Aged ,030304 developmental biology ,QS, sensory organs ,Pharmacology ,Plants, Medicinal ,business.industry ,Plant Part ,Coffea ,Traditional medicine ,biology.organism_classification ,language.human_language ,UR, Use report ,QA, alimentary system and metabolism ,Cattle ,Horse Diseases ,GNS, German native speaker ,Antimicrobial ,Medicine, Traditional ,business ,Phytotherapy - Abstract
Ethnopharmacological relevance In the pre-antibiotic era, a broad spectrum of medicinal plants was used to treat livestock. This knowledge was neglected in European veterinary medicine for decades but kept alive by farmers. Emergence of multidrug resistant bacterial strains requires a severely restricted use of antibiotics in veterinary medicine. We conducted a survey on the ethnoveterinary knowledge of farmers in the bilingual (French and German speaking) Western region of Switzerland, namely the cantons of Fribourg, Neuchâtel and Jura, and in the French speaking part of the canton of Bern. Aim of the study To find out whether differences exist in plants used by farmers in French speaking and bilingual regions of Switzerland as compared to our earlier studies conducted in Switzerland. Additional focus was on plants that are used in diseases which commonly are treated with antimicrobials, on plants used in skin afflictions, and on plants used in animal species such as horses, for which the range of veterinary medicinal products is limited. Material and methods We conducted in 2015 semistructured interviews with 62 dialog partners, mainly cattle keeping farmers but also 18 horse keeping farmers. Of these, 41 were native French (FNS) and 21 native German speakers (GNS). Detailed information about homemade herbal remedies (plant species, plant part, manufacturing process) and the corresponding use reports (target animal species, category of use, route of administration, dosage, source of knowledge, frequency of use, last time of use and farmers satisfaction) were collected. Results A total of 345 homemade remedies were reported, of which 240 contained only one plant species (Homemade Single Species Herbal Remedy Reports; HSHR). A total of 289 use reports (UR) were mentioned for the 240 HSHR, and they comprised 77 plant species belonging to 41 botanical families. Of these, 35 plant species were solely reported from FNS, 20 from GNS, and 22 from both. Taking into account earlier ethnoveterinary studies conducted in Switzerland only 10 (FNS) and 6 (GNS) plant species connected with 7% of FNS and GNS UR respectively were “unique” to the respective language group. The majority of the UR (219) was for treatment of cattle, while 38 UR were intended to treat horses. The most UR were for treatment of gastrointestinal and skin diseases. The most frequently mentioned plants were Linum usitatissimum L., Coffea L., Matricaria chamomilla L., Camellia sinensis (L.) Kuntze, and Quercus robur L. for gastrointestinal diseases, and Calendula officinalis L., Hypericum perforatum L. and Sanicula europaea L. for skin afflictions. Conclusion No clear differences were found between the medicinal plants used by French native speakers and German native speakers. Several of the reported plants seem to be justified to widen the spectrum of veterinary therapeutic options in gastrointestinal and dermatological disorders in cattle and horses, and to reduce, at least to a certain degree, the need for antibiotic treatments. Our findings may help to strengthen the role of medicinal plants in veterinary research and practice, and to consider them as a further measure in official strategies for lowering the use of antibiotics., Graphical abstract Image 1
- Published
- 2020
22. Inhibition of porcine detrusor contractility by the flavonoid fraction of Bryophyllum pinnatum – a potential phytotherapeutic drug for the treatment of the overactive bladder syndrome
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Daniel Eberli, Olivier Potterat, Ana Paula Simões-Wüst, Rudolf Brenneisen, Cornelia Betschart, Martin Schnelle, M Mennet-von Eiff, M De Mieri, Karin Fürer, U von Mandach, and Matthias Hamburger
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Kalanchoe ,Detrusor muscle ,medicine.medical_specialty ,Swine ,Urinary Bladder ,Flavonoid ,Pharmaceutical Science ,Bufadienolide ,In Vitro Techniques ,urologic and male genital diseases ,Contractility ,chemistry.chemical_compound ,Internal medicine ,Drug Discovery ,medicine ,Animals ,Bryophyllum pinnatum ,Oxybutynin ,Flavonoids ,Pharmacology ,chemistry.chemical_classification ,Molecular Structure ,biology ,Plant Extracts ,Urinary Bladder, Overactive ,Muscle, Smooth ,biology.organism_classification ,medicine.disease ,Bufanolides ,Plant Leaves ,Muscle relaxation ,medicine.anatomical_structure ,Endocrinology ,Complementary and alternative medicine ,chemistry ,Overactive bladder ,Molecular Medicine ,Female ,Muscle Contraction ,Phytotherapy ,medicine.drug - Abstract
Aims: To determine if the phytotherapeutic agent, Bryophyllum pinnatum, could serve as an alternative drug for the overactive bladder syndrome, and to characterise the fraction responsible for the inhibition of detrusor contractility. Methods: Fractions were prepared from the MeOH extract of B. pinnatum and further analysed by HPLCPDA-MS. Detrusor muscle strips were prepared from porcine bladders and the electrically induced muscle contractility measured by organ bath. The effect of B. pinnatum leaf press juice (2.5–10%), a flavonoid fraction (0.1–1 mg/ml), and a bufadienolide fraction (0.1–40 μg/ml) on detrusor contractility was assessed and compared with controls (polar fraction (0.5–5 mg/ml) and oxybutynin (10−8–10−6 M)). Results: The press juice, at a concentration of 10% led to a reduction of detrusor contractility. Bladder strips treated with the flavonoid fraction showed a significant reduction of the contractility to 21.3 ± 5.2% (1 mg/ml) while the bufadienolide fraction had no inhibitory effect in the investigated concentrations. The polar fraction showed a reduction of the contractility in a pH-dependent fashion. At 10 −6 M concentration oxybutynin reduced the detrusor contractility to 21.9 ± 4.7%. Conclusions: The flavonoid fraction of Bryophyllum pinnatum reduces the porcine detrusor contractility in a dose- and time-dependent manner. Fractions from B. pinnatum may be a new pharmacological approach for the treatment of OAB. © 2015 Published by Elsevier GmbH.
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- 2015
23. Identification of two new phenathrenones and a saponin as antiprotozoal constituents of Drypetes gerrardii
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Matthias Hamburger, Marcel Kaiser, Yoshie Hata, Samad Nejad Ebrahimi, Maria De Mieri, Tsholofelo Mokoka, Gerda Fouche, Reto Brun, and Olivier Potterat
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chemistry.chemical_classification ,biology ,Stereochemistry ,medicine.drug_class ,Saponin ,Trypanosoma brucei rhodesiense ,Plant Science ,biology.organism_classification ,Biochemistry ,High-performance liquid chromatography ,In vitro ,chemistry ,In vivo ,parasitic diseases ,Antiprotozoal ,medicine ,Putranjivaceae ,Plasmodium berghei ,Agronomy and Crop Science ,Biotechnology - Abstract
In an in vitro screen of 206 extracts from South African plants, the CH2Cl2/MeOH (1:1) stem extract of Drypetes gerrardii Hutch. var gerrardii (Putranjivaceae) inhibited Plasmodium falciparum and Leishmania donovani (IC50s of 0.50 and 7.31 μg/ml, respectively). In addition, the CH2Cl2/MeOH (1:1) extract of the leaves showed activity against Trypanosoma brucei rhodesiense (IC50 of 12.1 μg/ml). The active constituents were tracked by HPLC-based activity profiling, and isolated by preparative and semi-preparative RP-HPLC chromatography. Their structures were established by HRESIMS, and 1D and 2D NMR (1H, 13C, COSY, HMBC, HSQC, and NOESY). From the stem extract, a new phenanthrenone derivative, drypetenone D (1), and a phenanthrenone heterodimer, drypetenone E (2), were isolated. Compound 1 showed potent in vitro activity against P. falciparum (IC50 of 0.9 μM) with a selectivity index (SI) of 71, as calculated from cytotoxicity data for L-6 cells. These data qualified 1 for in vivo assessment in the Plasmodium berghei mouse model, but the compound turned out to be inactive. Compound 2 also exhibited good in vitro antiplasmodial activity (IC50 of 2.0 μM) and selectivity (SI 31). From the leaf extract, the saponin putranoside A (3) was isolated and identified. Compound 3 showed weak in vitro trypanocidal activity, with an IC50 of 18.0 μM, and a SI of 4.
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- 2014
24. Mechanism of Chemical Degradation and Determination of Solubility by Kinetic Modeling of the Highly Unstable Sesquiterpene Lactone Nobilin in Different Media
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Matthias Hamburger, Peter Altmann, Markus Neuburger, Georgios Imanidis, Maria De Mieri, Sheela Verjee, and Ursula Thormann
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Order of reaction ,Chemistry ,Kinetics ,Pharmaceutical Science ,Crystallography, X-Ray ,Intestinal absorption ,Sesquiterpenes, Germacrane ,Models, Chemical ,Solubility ,Computational chemistry ,Organic chemistry ,Chemical stability ,Particle size ,Particle Size ,Dissolution ,Chromatography, High Pressure Liquid ,Chemical decomposition - Abstract
The objective of this work was first to investigate the chemical degradation of the sesquiterpene lactone nobilin and determine its solubility under conditions of concurrent degradation for partially amorphous starting material; second, to determine the effect of biorelevant media used in the in vitro measurement of intestinal absorption on degradation and solubility of nobilin. Purely aqueous medium (aq-TMCaco ), fasted and fed state simulated intestinal fluid (FaSSIF-TMCaco and FeSSIF-TMCaco ), and two liposomal formulations (LiposomesFaSSIF and LiposomesFeSSIF ) with the same lipid concentration as FaSSIF-TMCaco and FeSSIF-TMCaco were used. Degradation products were identified by nuclear magnetic resonance and X-ray crystallography and the order of reaction kinetics was determined. Solubility was deduced with a mathematical model encompassing dissolution, degradation, and reprecipitation kinetics that took into account particle size distribution of the solid material. Degradation mechanism of nobilin involved water-catalyzed opening of the lactone ring and transannular cyclization resulting in five degradation products. Degradation followed first-order kinetics in aq-TMCaco and FaSSIF-TMCaco , and higher-order kinetics in FeSSIF-TMCaco and the two liposomal formulations, whereas degradation in the latter media was diminished. Solubility of nobilin increased in the order: aq-TMCaco < FaSSIF-TMCaco , < LiposomesFaSSIF < FeSSIF-TMCaco < LiposomesFeSSIF . Improvement of stability and solubility was consistent with the incorporation of the nobilin molecule into colloidal lipid particles. The developed kinetic model is proposed to be a useful tool for deducing solubility under dynamic conditions.
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- 2014
25. HPLC-based activity profiling for antiplasmodial compounds in the traditional Indonesian medicinal plant Carica papaya L
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Markus Neuburger, Marcel Kaiser, Samad Nejad Ebrahimi, Melanie Raith, Reto Brun, Stefanie Zimmermann, Tasqiah Julianti, Matthias Hamburger, and Maria De Mieri
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Spectrometry, Mass, Electrospray Ionization ,Magnetic Resonance Spectroscopy ,Plasmodium berghei ,Decoction ,Mass Spectrometry ,Antimalarials ,Mice ,Rutin ,chemistry.chemical_compound ,Flavonols ,Parasitic Sensitivity Tests ,In vivo ,parasitic diseases ,Drug Discovery ,Animals ,Bioassay ,Chromatography, High Pressure Liquid ,Medicine, East Asian Traditional ,Pharmacology ,chemistry.chemical_classification ,Antiparasitic Agents ,biology ,Traditional medicine ,Carica ,Plant Extracts ,Circular Dichroism ,biology.organism_classification ,Malaria ,Plant Leaves ,Disease Models, Animal ,chemistry ,Biochemistry ,Indonesia ,Female ,Carpaine - Abstract
Ethnopharmacological relevance Leaf decoctions of Carica papaya have been traditionally used in some parts of Indonesia to treat and prevent malaria. Leaf extracts and fraction have been previously shown to possess antiplasmodial activity in vitro and in vivo. Materials and methods Antiplasmodial activity of extracts was confirmed and the active fractions in the extract were identified by HPLC-based activity profiling, a gradient HPLC fractionation of a single injection of the extract, followed by offline bioassay of the obtained microfractions. For preparative isolation of compounds, an alkaloidal fraction was obtained via adsorption on cationic ion exchange resin. Active compounds were purified by HPLC–MS and MPLC–ELSD. Structures were established by HR-ESI-MS and NMR spectroscopy. For compounds 5 and 7 absolute configuration was confirmed by comparison of experimental and calculated electronic circular dichroism (ECD) spectroscopy data, and by X-ray crystallography. Compounds were tested for bioactivity in vitro against four parasites (Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum), and in the Plasmodium berghei mouse model. Results Profiling indicated flavonoids and alkaloids in the active time windows. A total of nine compounds were isolated. Four were known flavonols – manghaslin, clitorin, rutin, and nicotiflorin. Five compounds isolated from the alkaloidal fraction were piperidine alkaloids. Compounds 5 and 6 were inactive carpamic acid and methyl carpamate, while three alkaloids 7–9 showed high antiplasmodial activity and low cytotoxicity. When tested in the Plasmodium berghei mouse model, carpaine (7) did not increase the survival time of animals. Conclusions The antiplasmodial activity of papaya leaves could be linked to alkaloids. Among these, carpaine was highly active and selective in vitro. The high in vitro activity could not be substantiated with the in vivo murine model. Further investigations are needed to clarify the divergence between our negative in vivo results for carpaine, and previous reports of in vivo activity with papaya leaf extracts.
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- 2014
26. GABAA receptor modulation by piperine and a non-TRPV1 activating derivative
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Matthias Hamburger, Christooph Schwarzer, Igor Baburin, Barbara Strommer, Steffen Hering, Janine Zaugg, Sophia Khom, Thomas Erker, Juliane Hintersteiner, Angela Schöffmann, and Thomas Schwarz
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Male ,Polyunsaturated Alkamides ,TRPV1 channels ,medicine.drug_class ,TRPV1 ,TRPV Cation Channels ,Behavioural pharmacology ,Stimulation ,Motor Activity ,Pharmacology ,Biochemistry ,Anxiolytic ,Article ,GABAA-rho receptor ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Alkaloids ,0302 clinical medicine ,Piperidines ,medicine ,Animals ,Benzodioxoles ,GABA Modulators ,Receptor ,ComputingMethodologies_COMPUTERGRAPHICS ,030304 developmental biology ,2-Microelectrode voltage clamp technique ,0303 health sciences ,Chemistry ,GABAA receptor ,Piperine ,GABAA receptors ,Receptors, GABA-A ,Mice, Inbred C57BL ,nervous system ,Piper nigrum ,030217 neurology & neurosurgery ,Protein Binding - Abstract
Graphical abstract, The action of piperine (the pungent component of pepper) and its derivative SCT-66 ((2E,4E)-5-(1,3-benzodioxol-5-yl))-N,N-diisobutyl-2,4-pentadienamide) on different gamma-aminobutyric acid (GABA) type A (GABAA) receptors, transient-receptor-potential-vanilloid-1 (TRPV1) receptors and behavioural effects were investigated. GABAA receptor subtypes and TRPV1 receptors were expressed in Xenopus laevis oocytes. Modulation of GABA-induced chloride currents (IGABA) by piperine and SCT-66 and activation of TRPV1 was studied using the two-microelectrode-voltage-clamp technique and fast perfusion. Their effects on explorative behaviour, thermoregulation and seizure threshold were analysed in mice. Piperine acted with similar potency on all GABAA receptor subtypes (EC50 range: 42.8 ± 7.6 μM (α2β2)–59.6 ± 12.3 μM (α3β2)). IGABA modulation by piperine did not require the presence of a γ2S-subunit, suggesting a binding site involving only α and β subunits. IGABA activation was slightly more efficacious on receptors formed from β2/3 subunits (maximal IGABA stimulation through α1β3 receptors: 332 ± 64% and α1β2: 271 ± 36% vs. α1β1: 171 ± 22%, p
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- 2013
27. Development and full validation of an UPLC-MS/MS method for the determination of an anti-allergic indolinone derivative in rat plasma, and application to a preliminary pharmacokinetic study
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Mouhssin Oufir, Matthias Hamburger, Chethan Sampath, and Veronika Butterweck
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Male ,Indoles ,Clinical Biochemistry ,Derivative ,Tandem mass spectrometry ,Biochemistry ,High-performance liquid chromatography ,I²S ,Analytical Chemistry ,Rats, Sprague-Dawley ,Drug Stability ,Isomerism ,Pharmacokinetics ,Limit of Detection ,Tandem Mass Spectrometry ,Anti-Allergic Agents ,Animals ,Chromatography, High Pressure Liquid ,Detection limit ,Chromatography ,Chemistry ,Extraction (chemistry) ,Reproducibility of Results ,Cell Biology ,General Medicine ,Rats ,Regression Analysis ,Anti allergy - Abstract
The natural product (E,Z)-3-(4-hydroxy-3,5-dimethoxybenzylidene)indolin-2-one (indolinone) was identified some years ago as a nanomolar inhibitor of FcɛRI-receptor dependent mast cell degranulation. To further explore the potential of the compound, we established an UPLC-MS/MS assay for dosage in rat plasma. The method was fully validated according to FDA Guidance for industry. Results of this validation and long term stability study demonstrate that the method in lithium heparinized rat plasma is specific, accurate, precise and capable of producing reliable results according to recommendations of international guidelines. The method was validated with a LLOQ of 30.0 ng/mL and an ULOQ of 3000 ng/mL. The response versus concentration data were fitted with a first order polynomial with 1/X(2) weighting. No matrix effect was observed when using three independent sources of rat plasma. The average extraction recovery was consistent over the investigated range. This validation in rat plasma demonstrated that indolinone was stable for 190 days when stored below -65 °C; for 4 days at 10 °C in the autosampler; for 4h at RT, and during three successive freeze/thaw cycles at -65 °C. Preliminary pharmacokinetic data were obtained in male Sprague-Dawley rats (2 mg/kg BW i.v.). Blood samples taken from 0 to 12 h after injection were collected, and data analyzed with WinNonlin. A short half-life (4.30±0.14 min) and a relatively high clearance (3.83±1.46 L/h/kg) were found.
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- 2012
28. Disesquiterpene and sesquiterpene coumarins from Ferula pseudalliacea, and determination of their absolute configurations
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Marcel Kaiser, Stefanie Zimmermann, Peyman Salehi, Samad Nejad Ebrahimi, Hamid Reza Khavasi, Ahmad Reza Gohari, Dara Dastan, and Matthias Hamburger
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Stereochemistry ,Plasmodium falciparum ,Plant Science ,Horticulture ,Sesquiterpene ,Plant Roots ,Biochemistry ,Antimalarials ,chemistry.chemical_compound ,Coumarins ,Nuclear Magnetic Resonance, Biomolecular ,Molecular Biology ,Apiaceae ,Molecular Structure ,biology ,Strain (chemistry) ,Absolute configuration ,Absolute (perfumery) ,General Medicine ,Time-dependent density functional theory ,biology.organism_classification ,Coumarin ,Ferula ,chemistry ,Sesquiterpenes ,Two-dimensional nuclear magnetic resonance spectroscopy - Abstract
The first disesquiterpene coumarin, sanandajin, five sesquiterpene coumarins, kamolonol acetate, fekrynol acetate, ethyl galbanate, methyl galbanate, farnesiferol B, and a sesquiterpene, aristolone, were isolated from a n-hexane extract of Ferula pseudalliacea roots. The structures were elucidated by 1D and 2D NMR, HR-ESIMS data, and kamolonol acetate was confirmed by single-crystal X-ray analysis. The absolute configuration of compounds was established by comparison of experimental and simulated ECD spectra using time dependence density function theory (TDDFT). In vitro antiplasmodial activity against Plasmodium falciparum K1 strain was determined. sanandajin, kamolonol acetate and methyl galbanate showed moderate antiplasmodial activity, with IC(50) values of 2.6, 16.1 and 7.1 μM, respectively.
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- 2012
29. Renaissance remedies: Antiplasmodial protostane triterpenoids from Alisma plantago-aquatica L. (Alismataceae)
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Matthias Hamburger, Michael Adams, Sofia Gschwind, Stefanie Zimmermann, and Marcel Kaiser
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Alismataceae ,medicine.drug_class ,Plasmodium falciparum ,Drug Evaluation, Preclinical ,Ethyl acetate ,Pharmacognosy ,Antimalarials ,Inhibitory Concentration 50 ,chemistry.chemical_compound ,Triterpene ,Drug Discovery ,Alisma ,Botany ,Alisma plantago-aquatica ,medicine ,Cholestenones ,Pharmacology ,chemistry.chemical_classification ,Molecular Structure ,biology ,Traditional medicine ,Plant Extracts ,biology.organism_classification ,Triterpenes ,Terpenoid ,chemistry ,Antiprotozoal - Abstract
Aim of the study In a preliminary screen of extracts from plants used as antimalarial remedies used in Europe in the 16th and 17th, the ethyl acetate extract of Alisma plantago-aquatica L. (Alismataceae) was active against Plasmodium falciparum K1 strain with 77% growth inhibition at 4.9 μg/ml. The aim of this study was to isolate and identify the substances responsible for this antiplasmodial activity. Materials and methods With HPLC-based activity profiling in combination with HPLC hyphenated methods (HPLC–PDA, –MSn, HR–MS, and off-line microprobe NMR) the activity was assigned to time windows, and the substances contained therein were characterised chemically. The active compounds were isolated with semi-preparative HPLC and structures were elucidated with high resolution mass spectrometry, and 1D and 2D NMR spectroscopy. Results Four compounds were isolated and identified as protostane triterpenoids alisol A, alisol B 11-monoacetate, alisol B 23-monoacetate, and alisol G. Their IC 50 s against Plasmodium falciparum ranged from 5.4 to 13.8 μM. Conclusions This is the first report of antiplasmodial activity from protostanes triterpenoids, and the first result of our ongoing project of screening for antiprotozoal natural products from remedies used in European renaissance medicine.
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- 2011
30. Malaria in the renaissance: Remedies from European herbals from the 16th and 17th century
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Matthias Hamburger, Wandana Alther, Martin Kluge, Michael Adams, and Michael Kessler
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Pharmacology ,Plants, Medicinal ,History ,biology ,Traditional medicine ,Plasmodium vivax ,Materia medica ,The Renaissance ,Quartan malaria ,Plasmodium malariae ,biology.organism_classification ,medicine.disease ,Malaria ,Europe ,History, 17th Century ,Antimalarials ,History, 16th Century ,Ethnopharmacology ,Drug Discovery ,medicine ,Humans ,Plant Preparations ,Tertian ,Phytotherapy - Abstract
Background From antiquity up into the 20th century tertian and quartan malaria which are caused by the parasites Plasmodium vivax and Plasmodium malariae were widespread in Central Europe. Hundreds of different remedies against malaria can be found in herbals from the Renaissance. Aim of the study To document and discuss from a modern pharmacological viewpoint the old remedies described in eight 16th and 17th century herbals written in German. Materials and methods Eight of the most important herbals of the 16th and17th century including Bock (1577), Fuchs (1543), Matthiolus (1590), Lonicerus (1560), Brunfels (1532), Zwinger (1696), and Tabernaemontanus (1591 and 1678) were searched for terms related to malaria, and documented plants and recipes described for its treatment. Additionally the overlapping of these remedies with those in De Materia Medica by the Greek physician Dioscorides was studied. Results Three hundred and fourteen taxa were identified in the herbals for this indication. Recent pharmacological data was found for just 5% of them. The influence of De Materia Medica was shown to be negligible with only 3.5% of the remedies in common. Conclusions European Renaissance herbals may be a valuable source of information for the selection of plants for focussed antiplasmodial screening programmes, but have received only little scientific attention. Antimalarial remedies from these herbals must be viewed as independent sources of knowledge separate from Dioscorides’ De Materia Medica.
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- 2011
31. Antileishmanial activity of 12-methoxycarnosic acid from Salvia repens Burch. ex Benth. (Lamiaceae)
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Gerda Fouche, Xolani K Peter, Matthias Hamburger, N. Moodley, Neil A. Koorbanally, Reto Brun, Marcel Kaiser, Vinesh Maharaj, Michael Adams, and Tsholofelo Mokoka
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Salvia repens ,biology ,Abietane diterpene ,medicine.drug_class ,Leishmania donovani ,Plant Science ,Antileishmanial activity ,biology.organism_classification ,High-performance liquid chromatography ,Repens ,chemistry.chemical_compound ,chemistry ,HPLC profiling ,Botany ,parasitic diseases ,Antiprotozoal ,medicine ,Lamiaceae ,Diterpene ,Amastigote ,12-Methoxycarnosic acid ,Abietane - Abstract
In South Africa, Salvia repens is used traditionally to treat sores, stomach ache and diarrhoea. The high performance liquid chromatography (HPLC)-based activity profiling of S. repens whole plant extract showed an active abietane diterpene, identified as 12-methoxycarnosic acid (1) which showed antiprotozoal activity against axenically grown Leishmania donovani amastigotes with an IC50 of 0.75 μM with marginal cytotoxicity against the L6-cells (IC50, 17.3 μM).
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- 2014
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32. Separation and detection of all phosphoinositide isomers by ESI-MS
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Johannes Rogger, Sabine Kiefer, Peter Küenzi, Matthias Hamburger, Anna Melone, Ann C. Mertz, and Anna Koryakina
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Spectrometry, Mass, Electrospray Ionization ,Electrospray ,Chromatography ,Chemistry ,Electrospray ionization ,Clinical Biochemistry ,Pharmaceutical Science ,Reversed-phase chromatography ,Chromatography, Ion Exchange ,Phosphatidylinositols ,Mass spectrometry ,High-performance liquid chromatography ,Analytical Chemistry ,chemistry.chemical_compound ,Isomerism ,Biochemistry ,Liquid chromatography–mass spectrometry ,Isotope Labeling ,Labelling ,Drug Discovery ,Humans ,Phosphatidylinositol ,Cells, Cultured ,Spectroscopy - Abstract
Phosphoinositides (PIs) play fundamental roles as signalling molecules in numerous cellular processes. Direct analysis of PIs is typically accomplished by metabolic labelling with (3)H-inositol or inorganic (32)P followed by deacylation, ion-exchange chromatography and flow scintillation detection. This analysis is laborious, time-consuming, and involves massive amounts of radioactivity. To overcome these limitations we established a robust, non-radioactive LC-ESI-MS assay for the separation and analysis of deacylated PIs that allows discrimination of all isomers without the need for radioactive labelling. We applied the method to various cell types to study the PI levels upon specific stimulation.
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- 2010
33. HPLC-profiling for antiplasmodial compounds—3-Methoxycarpachromene from Pistacia atlantica
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Reto Brun, Michael Adams, Inken Plitzko, Marcel Kaiser, and Matthias Hamburger
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Pharmacology ,chemistry.chemical_classification ,Chromatography ,biology ,Stereochemistry ,Organic Chemistry ,Flavonoid ,Ethyl acetate ,Pharmaceutical Science ,Plasmodium falciparum ,Plant Science ,biology.organism_classification ,Biochemistry ,High-performance liquid chromatography ,Analytical Chemistry ,chemistry.chemical_compound ,Complementary and alternative medicine ,chemistry ,Drug Discovery ,Molecular Medicine ,Anacardiaceae ,Pistacia atlantica ,Agronomy and Crop Science ,Off line ,Biotechnology - Abstract
In the course of a medium throughput screen of 640 plant extracts for antimalarial activity an ethyl acetate extract of Pistacia atlantica DC. (Anacardiaceae) was found to be active. With analytical scale time-based HPLC separation and testing for antiplasmodial activity in combination with hyphenated methods (HPLC-PDA, -MSn, HR-MS, off line microprobe NMR) the active substance was identified. Subsequent isolation and structure elucidation yielded flavone 3-methoxycarpachromene. It had an IC50 of 3.4 μM towards Plasmodium falciparum K1 strain.
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- 2009
34. A comprehensive metabolite profiling of Isatis tinctoria leaf extracts
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Tobias Mohn, Olivier Potterat, and Matthias Hamburger
- Subjects
Electrospray ,Porphyrins ,Chemical structure ,Pharmaceutical Science ,Plant Science ,Horticulture ,Mass spectrometry ,Biochemistry ,High-performance liquid chromatography ,Lignans ,Indole Alkaloids ,Analytical Chemistry ,Alkaloids ,Glucosides ,Liquid chromatography–mass spectrometry ,Chromatography detector ,Drug Discovery ,Botany ,Isatis ,Molecular Biology ,Chromatography, High Pressure Liquid ,Flavonoids ,Pharmacology ,Plants, Medicinal ,Chromatography ,Molecular Structure ,Traditional medicine ,biology ,Cyclohexanones ,Chemistry ,Fatty Acids ,Organic Chemistry ,Electron Spin Resonance Spectroscopy ,General Medicine ,biology.organism_classification ,Carotenoids ,Isatis tinctoria ,Plant Leaves ,Complementary and alternative medicine ,Metabolite profiling ,Molecular Medicine - Abstract
A broad-based characterisation of a pharmacologically active dichloromethane extract from Isatis tinctoria leaves was carried out. For a comprehensive picture we also included the polar constituents of I. tinctoria (MeOH extract) and for comparative purposes, the taxonomically closely related plant I. indigotica. Diode array detector, evaporative light scattering detector, atmospheric pressure chemical ionisation and electrospray ionisation mass spectrometry, and electrospray ionisation time-of-flight mass spectrometry detectors were used in parallel to ensure a wide coverage of secondary metabolites with highly diverging analytical properties. Off-line microprobe nuclear magnetic resonance spectroscopy after peak purification by semi-preparative high-pressure liquid chromatography served for structure elucidation of some minor constituents. More than 65 compounds belonging to various structural classes such as alkaloids, flavonoids, fatty acids, porphyrins, lignans, carotenoids, glucosinolates and cyclohexenones were unambiguously identified, and tentative structures were proposed for additional compounds. Numerous compounds were identified for the first time in the genus Isatis, and an indolic alkaloid was discovered.
- Published
- 2009
35. Medicinal herbs for the treatment of rheumatic disorders—A survey of European herbals from the 16th and 17th century
- Author
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Michael Adams, Matthias Hamburger, Caroline Berset, and Michael Kessler
- Subjects
Pharmacopoeias as Topic ,Pharmacology ,medicine.medical_specialty ,Plants, Medicinal ,Traditional medicine ,business.industry ,Herbal Medicine ,Plant composition ,Alternative medicine ,MEDLINE ,food and beverages ,Europe ,History, 17th Century ,History, 16th Century ,Rheumatic Diseases ,Ethnobotany ,Materia Medica ,Drug Discovery ,medicine ,Humans ,Medicinal herbs ,Medicine, Traditional ,Medicinal plants ,business ,Phytotherapy - Abstract
Ethnopharmacological relevance From the 16th up into the 18th century botanical and medicinal knowledge in Europe was documented and spread in magnificently illustrated herbals. For the most part modern science has neglected this source of knowledge and old remedies have not been systematically evaluated pharmacologically. Aim of the study Rheumatic disorders and chronic inflammatory and degenerative diseases of the musculoskeletal system were chosen in an attempt to discuss remedies described in the old herbals in the viewpoint of modern science. Materials and methods Five of the most important European herbals of the 16th and 17th century were searched for terms related to rheumatic diseases, and plants and recipes described for their treatment. An extensive search of the scientific data banks Medline and SciFinder scholar was done to find recent results concerning the phytochemistry and possible antiphlogistic activities of the plants. Results Sixty-three plants were identified in the herbals for this indication. More than half of them have shown in vitro or in vivo antiphlogistic activities. Conclusions European herbals may be a valuable source of information for the selection of plants for focussed screening programmes. Information contained in these herbals should be explored in a systematic manner.
- Published
- 2009
36. The content of indigo precursors in leaves ? a comparative study of selected accessions and post-harvest treatments
- Author
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Matthias Hamburger, Christine Oberthür, and Heidemarie Graf
- Subjects
chemistry.chemical_classification ,Chromatography ,biology ,Glycoside ,Plant Science ,General Medicine ,Indican ,Horticulture ,biology.organism_classification ,Biochemistry ,Indigo ,Isatis tinctoria ,chemistry.chemical_compound ,Pigment ,chemistry ,Indigo carmine ,Dry weight ,Indoxyl ,visual_art ,visual_art.visual_art_medium ,Molecular Biology - Abstract
We recently clarified the nature of indigo precursors in woad (Isatis tinctoria L.), by identifying the major indoxyl glycoside as isatan A (indoxyl-3-O-(6'-O-malonyl-beta-D-ribohexo-3-ulopyranoside)), and by correcting the structure of the related isatan B (indoxyl-3-O-beta-D-ribohexo-3-ulopyranoside). A quantitative densitometric assay for isatans A and B, and indican, was established and validated. HPTLC separation on silica gel was followed by densitometric analysis of indigoid pigments formed after treatment with dilute acid or base. The seasonal variation of indoxyl glycosides in woad leaves was investigated with first-year plants (rosette stage) of five defined I. tinctoria L. and one I. indigotica L. accessions. Isatan A content reached up to 7.6% of dry weight in I. tinctoria, and up to 21.8% in I. indigotica. The influence of various post-harvest treatments was studied. High concentrations of isatans A and B were found in freeze-dried leaf samples, whereas the content of indican was lowest. Conventional drying at ambient or 40 degrees C led to complete disappearance of isatans A and B. The concentration of indican, in contrast, was 3- to 5-fold higher in leaf samples submitted to drying at ambient and 40 degrees C, respectively.
- Published
- 2004
37. Rapid analysis of nucleotide-activated sugars by high-performance liquid chromatography coupled with diode-array detection, electrospray ionization mass spectrometry and nuclear magnetic resonance
- Author
-
Emerson Ferreira Queiroz, Kurt Hostettmann, Michael Ramm, Jean-Luc Wolfender, and Matthias Hamburger
- Subjects
Spectrometry, Mass, Electrospray Ionization ,Electrospray ,Magnetic Resonance Spectroscopy ,Electrospray ionization ,ANTIGEN ,Carbohydrates ,Analytical chemistry ,Mannose ,LIPOPOLYSACCHARIDE ,Mass spectrometry ,Nucleotide sugar ,Biochemistry ,High-performance liquid chromatography ,Analytical Chemistry ,chemistry.chemical_compound ,GDP-MANNOSE ,SOLVENT SUPPRESSION ,BIOSYNTHESIS ,Nucleotide ,Chromatography, High Pressure Liquid ,chemistry.chemical_classification ,SPECTROSCOPY ,Chromatography ,Nucleotides ,Organic Chemistry ,PSEUDOMONAS-AERUGINOSA ,General Medicine ,GENE ,chemistry ,ESCHERICHIA-COLI ,ANIGOZANTHOS-PREISSII ,Guanosine diphosphate mannose - Abstract
A generally applicable method for HPLC analysis of sugar nucleotides was established. Separation was achieved using ion-pair chromatography on a reversed-phase column. Ion-pair reagents were selected and various parameters optimized with respect to separation of I I of the most important sugar nucleotides and compatibility with on-line detection by electrospray ionization MS and NMR. The method was applied to the on-line analysis of the GDP-D-mannose-4,6-dehydratase (Gmd) and GDP-4-keto-6-deoxy-D-mannose reductase (Rmd) catalyzed conversion of GDP-D-mannose to GDP-D-rhamnose. By LC-NMR, the intermediate product of the reaction was shown to be a mixture of GDP-4-keto-6-deoxy-D-mannose and GDP-3-keto-6-deoxy-D-mannose. Nucleotide co-factors of enzymatic reactions such as ATP and NADH did not interfere with the analysis of nucleotide-activated sugars. (C) 2004 Elsevier B.V. All rights reserved.
- Published
- 2004
38. Analysis of aspartyl peptide degradation products by high-performance liquid chromatography and high-performance liquid chromatography-mass spectrometry
- Author
-
Silvia De Boni, Matthias Hamburger, Christine Oberthür, and Gerhard K. E. Scriba
- Subjects
chemistry.chemical_classification ,Aspartic Acid ,Chromatography ,Resolution (mass spectrometry) ,Chemistry ,Organic Chemistry ,Electrophoresis, Capillary ,Peptide ,General Medicine ,Reversed-phase chromatography ,Tripeptide ,Hydrogen-Ion Concentration ,Mass spectrometry ,Biochemistry ,High-performance liquid chromatography ,Mass Spectrometry ,Analytical Chemistry ,Capillary electrophoresis ,Peptides ,Deamidation ,Chromatography, High Pressure Liquid - Abstract
A reversed-phase HPLC method for the analysis of degradation products of the model aspartyl tripeptides Phe-Asp-GlyNH2 and Gly-Asp-PheNH2 after incubation at pH 2 and 10 was developed. Most of the compounds could be separated with a gradient of acetonitrile in water containing 0.1% trifluoroacetic acid. Resolution of the isomeric pairs l -Phe-α- l -Asp-GlyNH2/ l -Phe-β- l -Asp-GlyNH2 and l -Phe-α- d -Asp-GlyOH/ l -Phe-β- d -Asp-GlyOH was achieved with a gradient of acetonitrile in phosphate buffer, pH 5.0. Under acidic conditions the major degradation pathway was cleavage of the peptide backbone amide bonds yielding dipeptides and amino acids, C-terminal deamidation as well as formation of succidinimyl peptides. At alkaline pH both deamidation of the C-terminal amide as well as isomerization and concomitant enantiomerization of Asp were observed. The peaks were identified both by reference substances and by online electrospray mass spectrometry. The results were compared to a previous developed capillary electrophoresis method. Diastereomeric pairs of peptides that could not be separated by capillary electrophoresis were resolved by HPLC while the separation of corresponding pairs of α- and β-Asp peptides was not always achieved by HPLC in contrast to capillary electrophoresis illustrating that both techniques can be complimentary in peptide analysis.
- Published
- 2004
39. Screening of entomopathogenic Deuteromycetes for activities on targets involved in degenerative diseases of the central nervous system
- Author
-
Matthias Hamburger, Karen Schmidt, Z Li, Barbara Schubert, B Huang, and Stefka Stoyanova
- Subjects
Antifungal Agents ,Cell Survival ,Drug Evaluation, Preclinical ,Mitochondria, Liver ,Central Nervous System Diseases ,Drug Discovery ,Animals ,Bioassay ,Beauveria ,Monoamine Oxidase ,Cells, Cultured ,Mycelium ,Pharmacology ,biology ,Sporothrix ,Biological activity ,Free Radical Scavengers ,Fungi imperfecti ,Fibroblasts ,biology.organism_classification ,Rats ,Biochemistry ,Cell culture ,Fermentation ,Chromatography, Thin Layer ,Mitosporic Fungi ,Paecilomyces ,Central Nervous System Agents - Abstract
A selection of 32 fungal strains, belonging to 8 genera of entomopathogenic Deuteromycetes collected in various provinces of China, were screened for activities on targets involved in degenerative diseases of the central nervous system. The strains were grown under various fermentation conditions, and a total of 256 different extracts were obtained. The bioassays included functional screens for NMDA antagonistic activity in stably transfected fibroblasts, for neuritogenic activities in PC-12 cells, and tests for MAO inhibitory and radical scavenging properties. Several extracts with promising activities were identified. Some Paecilomyces extracts induced pronounced axonal-like outgrowths in PC-12 cells. In Paecilomyces militaris RCEF 0095, the neuritogenic activity could be linked to yellow pigments. Three Beauveria and Paecilomyces strains showed radical scavenging properties, which could be localized in the extract by a bioautographic assay on TLC. An extract obtained from the mycelium of Paecilomyces tenuipes RCEF 0275 showed moderate MAO inhibitory activity, whereas extracts of Sporothrix chondracris RCEF 0187 antagonized NMDA receptor mediated cell toxicity.
- Published
- 2003
40. A simple method for preparation of d-rhamnose
- Author
-
Michael Ramm, Martina Lobe, and Matthias Hamburger
- Subjects
Lipopolysaccharides ,chemistry.chemical_classification ,Chromatography ,Rhamnose ,Hydrolysis ,Hydrophilic interaction chromatography ,Organic Chemistry ,Phenol extraction ,General Medicine ,Cleavage (embryo) ,Biochemistry ,Analytical Chemistry ,chemistry.chemical_compound ,Column chromatography ,chemistry ,Pseudomonas ,Pseudomonas syringae ,Monosaccharide - Abstract
A rapid procedure for the preparation of D-rhamnose from bacterial lipopolysaccharide (LPS) has been developed. It involves purification of LPS from Pseudomonas syringae pv. phaseolicola by phenol extraction and hydrophobic interaction chromatography (HIC), followed by mild hydrolysis and cleavage of the O-antigen into D-fucose and D-rhamnose. The monosaccharides were separated by column chromatography, and D-rhamnose recovered after filtration over Sephadex-LH 20.
- Published
- 2003
41. Dehydroevodiamine, isolated from the evodia Rutaecarpa, present in the traditional Chinese medicine Wu Chu Yu, has pro-arrhythmic effects in-vitro and in-vivo, which disappear at higher concentrations
- Author
-
M A Vos, Hiroki Takanari, Matthias Hamburger, M. Houtman, Igor Baburin, Malin K.B. Jonsson, Anja Schramm, Stefan Hering, Rosanne Varkevisser, and M. A. G. van der Heyden
- Subjects
Pharmacology ,Evodia rutaecarpa ,Traditional medicine ,Dehydroevodiamine ,In vivo ,business.industry ,Medicine ,Pharmacology (medical) ,Traditional Chinese medicine ,business - Published
- 2015
42. Application of liquid chromatography-atmospheric pressure ionization mass spectrometry in natural product analysis evaluation and optimization of electrospray and heated nebulizer interfaces
- Author
-
Matthias Hamburger and Shaolian Zhou
- Subjects
Electrospray ,Chemical ionization ,Desorption electrospray ionization ,Chromatography ,Chemistry ,Electrospray ionization ,Organic Chemistry ,Analytical chemistry ,Extractive electrospray ionization ,Atmospheric-pressure chemical ionization ,General Medicine ,Mass spectrometry ,Biochemistry ,Analytical Chemistry ,Direct electron ionization liquid chromatography–mass spectrometry interface - Abstract
A representative set of 46 secondary metabolites of plant and microbial origin was examined with electrospray and atmospheric pressure chemical ionization MS in both positive and negative ion mode, in order to evaluate the applicability of atmospheric pressure ionization LCMS as a tool for rapid identification and dereplication of bioactive compounds in the drug screening process. MS characteristics of different compound classes were determined on the basis of quasi-molecular ion and other adduct ion responses observed with the two LCMC interfaces. Interface parameters and LC mobile phase composition were optimized and an analytical protocol applicable to a wide range of secondary metabolites is proposed.
- Published
- 1996
43. Flavans and A-type proanthocyanidins from Prunus prostrata
- Author
-
Anna Rita Bilia, Matthias Hamburger, Ivano Morelli, and K. Hostetmann
- Subjects
Prunus prostrata ,biology ,Stereochemistry ,Catechin ,Plant Science ,General Medicine ,Horticulture ,biology.organism_classification ,Biochemistry ,Afzelechin ,chemistry.chemical_compound ,Monomer ,chemistry ,Proanthocyanidin ,Molecule ,Kaempferol ,Quercetin ,Molecular Biology - Abstract
A new natural dimeric A-type proanthocyanidin and two new monomeric flavanols have been isolated from Prunus prostrata and identified as ent-epiafzelechin (2 α → O → 7, 4 α → 8) quercetin, 5,7,2′,5′-tetrahydroxy-(2 R ,3 R )- flavan-3-ol and, 7-methoxy-(+)-catechin, respectively. The structurally related metabolites ent-epiafzelechin (2 α → O → 7, 4 α → 8) afzelechin, ent-epiafzelechin (2 α → O → 7, 4 α → 8) kaempferol, ent-epiafzelechin (2 α → O → 7, 4 α → 8) epicatechin, ent-epiafzelechin (2 α → O → 7, 4 α → 8) epiafzelechin, ent-epiafzelechin (2 α → O → 7, 4 α → 8) catechin, (+)-catechin and (−)-epicatechin were also isolated. Structure elucidation was achieved by extensive NMR (homo- and hetero-nuclear two-dimensional correlation, NOE difference, and selective INEPT experiments) and CD studies.
- Published
- 1996
44. Potential of Bryophyllum pinnatum as a detrusor relaxant: Effects of a bufadienolide-enriched fraction in a porcine bladder model
- Author
-
Cornelia Betschart, Ursula von Mandach, Karin Fürer, Ana Paula Simões-Wüst, Matthias Hamburger, Olivier Potterat, Martin Schnelle, Mónica Mennet, and S. Bachmann
- Subjects
chemistry.chemical_compound ,Complementary and alternative medicine ,biology ,Traditional medicine ,Chemistry ,Bryophyllum pinnatum ,Fraction (chemistry) ,Bufadienolide ,biology.organism_classification - Published
- 2016
45. Molluscicidal milliamines from Euphorbia milii var. hislopii
- Author
-
Matthias Hamburger, Andrew Marston, Carlos L. Zani, and Kurt Hostettmann
- Subjects
biology ,Euphorbia milii ,Euphorbiaceae ,Plant Science ,General Medicine ,Milliamine ,Horticulture ,biology.organism_classification ,Biochemistry ,Molluscicide ,Botany ,Spectral analysis ,Medicinal plants ,Molecular Biology - Abstract
From the latex of Euphorbia milii var. hislopii collected in Brazil, eight milliamines were isolated using a bioassay-guided protocol based on molluscicidal activity. Three were known milliamines A, D and E, the other five being new compounds of this class. Milliamine L, a dianthraniloyl peptide ester of ingenol, was found to be molluscicidal at 4 nM (2.5 μg 1 −1 ).
- Published
- 1993
46. Xanthones from Polygala nyikensis
- Author
-
Kurt Hostettmann, Andrew Marston, J. D. Msonthi, Matthias Hamburger, and Isabelle Sordat-Diserens
- Subjects
biology ,Stereochemistry ,Biological activity ,Plant Science ,General Medicine ,Horticulture ,Carbon-13 NMR ,Pathogenic fungus ,biology.organism_classification ,Biochemistry ,Polygala ,chemistry.chemical_compound ,chemistry ,Cladosporium cucumerinum ,Xanthone ,Polygalaceae ,Molecular Biology ,Dichloromethane - Abstract
The dichloromethane extract from the roots of Polygala nyikensis afforded four simple xanthones, two of which are new compounds. Their structures were established by chemical and spectroscopic methods (UV, EIMS, 1 H and 13 C NMR, NOE difference spectroscopy). 1,7-Dihydroxy-4-methoxyxanthone and 1,7-dihydroxy-3,5,6-trimethoxyxanthone exhibit antifungal activity against the plant pathogenic fungus Cladosporium cucumerinum .
- Published
- 1993
47. Dimeric xanthones from Garcinia livingstonei
- Author
-
Matthias Hamburger, Isabelle Sordat-Diserens, Colin B. Rogers, and Kurt Hostettmannt
- Subjects
Garcinia livingstonei ,Diene ,biology ,Stereochemistry ,Dimer ,Plant Science ,General Medicine ,Horticulture ,biology.organism_classification ,Mass spectrometry ,Biochemistry ,chemistry.chemical_compound ,Monomer ,chemistry ,visual_art ,Xanthone ,visual_art.visual_art_medium ,Molecule ,Bark ,Molecular Biology - Abstract
From the root bark of Garcinia livingstonei , three xanthone dimers have been isolated. Structure elucidation was achieved mainly by NMR and mass spectrometry, including extensive NOE difference measurements, and by comparison with monomeric prenylated xanthones previously isolated from the same plant. Garcilivin A–C are structurally related to 1,4,5-trihydroxy-3-(3-methylbut-2-enyl)-9 H -xanthen-9-one and formally derive from the corresponding diene via dimerization by a Diels-Alder-type reaction.
- Published
- 1992
48. Xanthones fromChironia krebsii
- Author
-
Jean-Luc Wolfender, Kurt Hostettmann, Matthias Hamburger, and J. D. Msonthi
- Subjects
Pharmacology ,chemistry.chemical_classification ,Stereochemistry ,Chemical structure ,Organic Chemistry ,Pharmaceutical Science ,Glycoside ,Plant Science ,General Medicine ,Horticulture ,Carbon-13 NMR ,Biochemistry ,Analytical Chemistry ,chemistry.chemical_compound ,Complementary and alternative medicine ,chemistry ,Chemotaxonomy ,Drug Discovery ,Xanthone ,Molecular Medicine ,Molecule ,Spectral analysis ,Molecular Biology ,Dichloromethane - Abstract
From a dichloromethane extract of the aerial parts and from a methanolic root extract of Chironia krebsii , 11 1-hydroxyxanthones and six xanthone glycosides have been isolated. The glycosides 5-hydroxy-3-methoxy-1- O -primeverosylxanthone, 1-hydroxy-3-methoxy-5- O -primeverosylxanthone, 5-hydroxy-3-methoxy-1- O -β- d -glucosyl-xanthone, 3,5,6,7,8-pentamethoxy-1- O -primeverosylxanthone are new natural products. Their structures were established by spectroscopic (UV, EIMS, D/CIMS, 1 H and 13 C NMR) and chemical methods.
- Published
- 1991
49. 7. Bioactivity in plants: the link between phytochemistry and medicine
- Author
-
Kurt Hostettmann and Matthias Hamburger
- Subjects
Toxicology ,Phytochemistry ,Plant Science ,General Medicine ,Biochemical engineering ,Horticulture ,Biology ,Molecular Biology ,Biochemistry - Abstract
The development of medicinal plant research over the last 30 years is reviewed with reference to the search for new active principles. Difficulties inherent to activity guided isolation and the specific requirements of bioassays are discussed. An overview is given on currently used systems for various bioactivities, with emphasis on simple bioassays for phytochemical laboratories. The progress in medicinal plant research is illustrated by selected examples of plant derived compounds of importance as drugs or pharmacological tools.
- Published
- 1991
50. Flavonol glycosides fromMonnina sylvatica
- Author
-
Matthias Hamburger, Ahmad Bashir, Pablo N. Solis, Mahabir P. Gupta, and Kurt Hostettmann
- Subjects
Magnetic Resonance Spectroscopy ,Stereochemistry ,Molecular Sequence Data ,Plant Science ,Horticulture ,Biochemistry ,Monnina ,chemistry.chemical_compound ,Enzymatic hydrolysis ,Moiety ,Kaempferols ,Molecular Biology ,Flavonoids ,chemistry.chemical_classification ,Molecular Structure ,biology ,Chemistry ,Glycoside ,General Medicine ,Nuclear magnetic resonance spectroscopy ,Plants ,biology.organism_classification ,Galactoside ,Carbohydrate Sequence ,Quercetin ,Polygalaceae ,Kaempferol - Abstract
A new kaempferol triglycoside and three known kaempferol glycosides, among them two apiosides, have been isolated from the aerial parts of Monnina sylvatica. The structures were established on the basis of acid and enzymatic hydrolysis and spectral data (UV, 1H and 13CNMR, NOE difference measurements, D/CI and FAB-MS) of the isolates and of some derivatives. The triglycoside kaempferol 3-O-beta-D-glucosyl-(1----2)-O-[alpha-L-rhamnosyl(1----6)]-beta-D- galactoside is a new natural product. The configuration of the apiosyl moiety in kaempferol 3-O-beta-D-apiosyl(1----2)-beta-D-galactoside and kaempferol 3-O-beta-D-apiosyl(1----2)-O-[alpha-L-rhamnosyl(1----6)]- beta-D-galactoside was established through NOE difference measurements on the peracetate.
- Published
- 1991
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