zur Suche springenzur Navigation springenzum Inhalt springen

Sortieren nach: Erscheinungsjahr Typ der Publikation

Zeige Ergebnisse 1 bis 10 von 39.

Publikation

Holzmeyer, L.; Hartig, A.-K.; Franke, K.; Brandt, W.; Muellner-Riehl, A. N.; Wessjohann, L. A.; Schnitzler, J.; Evaluation of plant sources for antiinfective lead compound discovery by correlating phylogenetic, spatial, and bioactivity data Proc. Natl. Acad. Sci. U.S.A. 117, 12444-12451, (2020) DOI: 10.1073/pnas.1915277117

The continued high rates of using antibiotics in healthcare and livestock, without sufficient new compounds reaching the market, has led to a dramatic increase in antimicrobial resistance, with multidrug-resistant bacteria emerging as a major public health threat worldwide. Because the vast majority of antiinfectives are natural products or have originated from them, we assessed the predictive power of plant molecular phylogenies and species distribution modeling in the search for clades and areas which promise to provide a higher probability of delivering new antiinfective compound leads. Our approach enables taxonomically and spatially targeted bioprospecting and supports the battle against the global antimicrobial crisis.
Publikation

Gladchuk, A.; Shumilina, J.; Kusnetsova, A.; Bureiko, K.; Billig, S.; Tsarev, A.; Alexandrova, I.; Leonova, L.; Zhukov, V. A.; Tikhonovich, I. A.; Birkemeyer, C.; Podolskaya, E.; Frolov, A.; High-Throughput Fingerprinting of Rhizobial Free Fatty Acids by Chemical Thin-Film Deposition and Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Methods Protoc. 3, 36, (2020) DOI: 10.3390/mps3020036

Fatty acids (FAs) represent an important class of metabolites, impacting on membrane building blocks and signaling compounds in cellular regulatory networks. In nature, prokaryotes are characterized with the most impressing FA structural diversity and the highest relative content of free fatty acids (FFAs). In this context, nitrogen-fixing bacteria (order Rhizobiales), the symbionts of legumes, are particularly interesting. Indeed, the FA profiles influence the structure of rhizobial nodulation factors, required for successful infection of plant root. Although FA patterns can be assessed by gas chromatography—(GC-) and liquid chromatography—mass spectrometry (LC-MS), sample preparation for these methods is time-consuming and quantification suffers from compromised sensitivity, low stability of derivatives and artifacts. In contrast, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) represents an excellent platform for high-efficient metabolite fingerprinting, also applicable to FFAs. Therefore, here we propose a simple and straightforward protocol for high-throughput relative quantification of FFAs in rhizobia by combination of Langmuir technology and MALDI-TOF-MS featuring a high sensitivity, accuracy and precision of quantification. We describe a step-by-step procedure comprising rhizobia culturing, pre-cleaning, extraction, sample preparation, mass spectrometric analysis, data processing and post-processing. As a case study, a comparison of the FFA metabolomes of two rhizobia species—Rhizobium leguminosarum and Sinorhizobium meliloti, demonstrates the analytical potential of the protocol.
Publikation

de Moura, P. H. B.; de Sousa, A. A.; Porzel, A.; Wessjohann, L. A.; Leal, I. C. R.; Martins, R. C. C.; Characterization of antibacterial proanthocyanidins of Dalbergia monetaria, an amazonian medicinal plant, by UHPLC-HRMS/MS Planta Med. 86, 858– 866, (2020) DOI: 10.1055/a-1170-8016

Dalbergia monetaria is an Amazonian plant whose bark is widely used to treat urinary tract infections. This paper describes a bio-guided study of ethanolic extracts from the bark and leaves of D. monetaria, in a search for metabolites active against human pathogenic bacteria. In vitro assays were performed against 10 bacterial strains, highlighting methicillin-sensitive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Fractioning of the extracts was performed using instrumental and classical techniques, and samples were characterized by UHPLC-HRMS/MS. Ethyl acetate fractions from bark and leaves showed similar antibacterial activities. EAFB is enriched in isoflavone C-glucosides and EAFL enriched in proanthocyanidins. Subfractions from EAFL presented higher activity and showed a complex profile of proanthocyanidins constructed by (epi)-cassiaflavan and (epi)-catechin units, including dimers, trimers and tetramers. The fragmentation pattern emphasized the neutral loss of cassiaflavan units by quinone-methide fission. Fraction SL7-6, constituted by (ent)-cassiaflavan-(ent)-cassiaflavan-(epi)-catechin isomers, showed the lowest MIC against the S. aureus and P. aeruginosa with values corresponding to 64 and 32 µg/mL, respectively. Cassiaflavan-proanthocyanidins have not been found previously in another botanical genus, except in Cassia, and the traditional medicinal use of D. monetaria might be related to the antibacterial activity of proanthocyanidins characterized in the species.
Publikation

da Silva, I. C. V.; Silva, I. C. V. d.; de Oliveira, P. F.; Oliveira, P. F. d.; Barbosa, G. M.; Wessjohann, L. A.; Cardozo-Filho, L.; Holandino, C.; Muzitano, M. F.; Leal, I. C. R.; Passiflora mucronata leaves extracts obtained from different methodologies: a phytochemical study based on cytotoxic and apoptosis activities of triterpenes and phytosterols constituents Braz. J. Pharm. Sci. 56, e17666, (2020) DOI: 10.1590/s2175-97902019000417666

Cancer is one of the most prevalent diseases worldwide and the natural products could be a source of bioactive compounds. Passiflora mucronata (PM) belongs to a very known vegetal genus, although, there are no studies about cytotoxic activity or isolated compounds. Different extracts from PM were obtained by liquid-liquid partition (P), Soxhlet (Sox) and supercritical fluid (SFE1-5) extraction techniques, being compared concerning their yields, chemical profile and cytotoxicity. The Sox extracts showed the highest yields (6.03%: hexane; 2.51%: dichloromethane) followed by SFE (from 4.34 to 1.63%) and partitions (1.06 and 2.26%). The hexane partition (HP) showed the best cytotoxic activity against K562 cell line (IC50 = 18.72 µg.mL-1). From HP, the following compounds were identified and analysed its cytotoxic activities: β-amyrin (IC50 = 3.92 µg.mL-1), β-sitosterol (IC50 = 3.37 µg.mL-1), stigmasterol (IC50 = 3.31 µg.mL-1) and oleanolic acid. Stigmasterol induced about 75% of K562 total apoptosis. The compounds were tested against MA-104 cell line and the selective index (SI) attributed (SI >10 for all compounds). This indicates good selectivity to K562 cell line at the expense of MA-104. This is the first time, identifying those compounds to PM .
Publikation

Chalo, D. M.; Kakudidi, E.; Origa-Oryem, H.; Namukobe, J.; Franke, K.; Yenesew, A.; Wessjohann, L. A.; Chemical constituents of the roots of Ormocarpum sennoides subsp. zanzibaricum Biochem. Syst. Ecol. 93, 104142, (2020) DOI: 10.1016/j.bse.2020.104142

Phytochemical investigation of the roots of O. sennoides subsp. zanzibaricum Brenan & J.B. Gillett resulted in the isolation of three biflavonoids (trime-chamaejasmin, (+)- chamaejasmin, (+)-liquiritigeninyl-(I-3,II-3)-naringenin), one bi-4-phenyldihydrocoumarin (diphysin), one isoflavan (glabridin), one triterpenoid (3-O-acetyloleanoic acid) and a phytosterol (β-sitosterol). Compounds were identified by detailed MS, 1D and 2D NMR spectroscopic analyses. Their absolute configurations were elucidated based on ECD spectra. The previously undescribed trime-chamaejasmin represents a bis-epi-chamaejasmenin C diastereomer. The chemophenetic significance is discussed in detail. The results contribute to the phytochemical characterization of the genus Ormocarpum and suggest a close chemophenetic relationship with other genera within the subfamily Papilionoideae. Furthermore, this report provides baseline data for comparing the two infraspecific taxa of O. sennoides (Willd.) DC.
Publikation

Bascuñana, P.; Möhle, L.; Brackhan, M.; Pahnke, J.; Fingolimod as a Treatment in Neurologic Disorders Beyond Multiple Sclerosis Drugs R. D. 20, 197-207, (2020) DOI: 10.1007/s40268-020-00316-1

Fingolimod is an approved treatment for relapsing–remitting multiple sclerosis (MS), and its properties in different pathways have raised interest in therapy research for other neurodegenerative diseases. Fingolimod is an agonist of sphingosine-1-phosphate (S1P) receptors. Its main pharmacologic effect is immunomodulation by lymphocyte homing, thereby reducing the numbers of T and B cells in circulation. Because of the ubiquitous expression of S1P receptors, other effects have also been described. Here, we review preclinical experiments evaluating the effects of treatment with fingolimod in neurodegenerative diseases other than MS, such as Alzheimer’s disease or epilepsy. Fingolimod has shown neuroprotective effects in different animal models of neurodegenerative diseases, summarized here, correlating with increased brain-derived neurotrophic factor and improved disease phenotype (cognition and/or motor abilities). As expected, treatment also induced reductions in different neuroinflammatory markers because of not only inhibition of lymphocytes but also direct effects on astrocytes and microglia. Furthermore, fingolimod treatment exhibited additional effects for specific neurodegenerative disorders, such as reduction of amyloid-β production, and antiepileptogenic properties. The neuroprotective effects exerted by fingolimod in these preclinical studies are reviewed and support the translation of fingolimod into clinical trials as treatment in neurodegenerative diseases beyond neuroinflammatory conditions (MS).
Publikation

Zoufal, V.; Mairinger, S.; Krohn, M.; Wanek, T.; Filip, T.; Sauberer, M.; Stanek, J.; Kuntner, C.; Pahnke, J.; Langer, O.; Measurement of cerebral ABCC1 transport activity in wild-type and APP/PS1-21 mice with positron emission tomography J. Cereb. Blood Flow Metab. 40, 954-965, (2020) DOI: 10.1177/0271678X19854541

Previous data suggest a possible link between multidrug resistance-associated protein 1 (ABCC1) and brain clearance of beta-amyloid (Aβ). We used PET with 6-bromo-7-[11C]methylpurine ([11C]BMP) to measure cerebral ABCC1 transport activity in a beta-amyloidosis mouse model (APP/PS1-21) and in wild-type mice aged 50 and 170 days, without and with pretreatment with the ABCC1 inhibitor MK571. One hundred seventy days-old-animals additionally underwent [11C]PiB PET scans to measure Aβ load. While baseline [11C]BMP PET scans detected no differences in the elimination slope of radioactivity washout from the brain (kelim) between APP/PS1-21 and wild-type mice of both age groups, PET scans after MK571 pretreatment revealed significantly higher kelim values in APP/PS1-21 mice than in wild-type mice aged 170 days, suggesting increased ABCC1 activity. The observed increase in kelim occurred across all investigated brain regions and was independent of the presence of Aβ plaques measured with [11C]PiB. Western blot analysis revealed a trend towards increased whole brain ABCC1 levels in 170 days-old-APP/PS1-21 mice versus wild-type mice and a significant positive correlation between ABCC1 levels and kelim. Our data point to an upregulation of ABCC1 in APP/PS1-21 mice, which may be related to an induction of ABCC1 in astrocytes as a protective mechanism against oxidative stress.
Publikation

Zoufal, V.; Mairinger, S.; Brackhan, M.; Krohn, M.; Filip, T.; Sauberer, M.; Stanek, J.; Wanek, T.; Tournier, N.; Bauer, M.; Pahnke, J.; Langer, O.; Imaging P-Glycoprotein Induction at the Blood–Brain Barrier of a β-Amyloidosis Mouse Model with 11C-Metoclopramide PET J. Nucl. Med. 61, 1050-1057, (2020) DOI: 10.2967/jnumed.119.237198

P-glycoprotein (ABC subfamily B member 1, ABCB1) plays an important role at the blood-brain barrier (BBB) in promoting clearance of neurotoxic β-amyloid (Aβ) peptides from the brain into the blood. ABCB1 expression and activity were found to be decreased in the brains of Alzheimer disease patients. Treatment with drugs that induce cerebral ABCB1 activity may be a promising approach to delay the build-up of Aβ deposits in the brain by enhancing clearance of Aβ peptides from the brain. The aim of this study was to investigate whether PET with the weak ABCB1 substrate radiotracer 11C-metoclopramide can measure ABCB1 induction at the BBB in a β-amyloidosis mouse model (APP/PS1-21 mice) and in wild-type mice. Methods: Groups of wild-type and APP/PS1-21 mice aged 50 or 170 d underwent 11C-metoclopramide baseline PET scans or scans after intraperitoneal treatment with the rodent pregnane X receptor activator 5-pregnen-3β-ol-20-one-16α-carbonitrile (PCN, 25 mg/kg) or its vehicle over 7 d. At the end of the PET scans, brains were harvested for immunohistochemical analysis of ABCB1 and Aβ levels. In separate groups of mice, radiolabeled metabolites of 11C-metoclopramide were determined in plasma and brain at 15 min after radiotracer injection. As an outcome parameter of cerebral ABCB1 activity, the elimination slope of radioactivity washout from the brain (k E,brain) was calculated. Results: PCN treatment resulted in an increased clearance of radioactivity from the brain as reflected by significant increases in k E,brain (from +26% to +54% relative to baseline). Immunohistochemical analysis confirmed ABCB1 induction in the brains of PCN-treated APP/PS1-21 mice with a concomitant decrease in Aβ levels. There was a significant positive correlation between k E,brain and ABCB1 levels in the brain. In wild-type mice, a significant age-related decrease in k E,brain was found. Metabolite analysis showed that most radioactivity in the brain comprised unmetabolized 11C-metoclopramide in all animal groups. Conclusion: 11C-metoclopramide can measure ABCB1 induction in the mouse brain without the need to consider an arterial input function and may find potential application in Alzheimer disease patients to noninvasively evaluate strategies to enhance the clearance properties of the BBB.
Publikation

Zoufal, V.; Wanek, T.; Krohn, M.; Mairinger, S.; Filip, T.; Sauberer, M.; Stanek, J.; Pekar, T.; Bauer, M.; Pahnke, J.; Langer, O.; Age dependency of cerebral P-glycoprotein function in wild-type and APPPS1 mice measured with PET J. Cereb. Blood Flow Metab. 40, 150-162, (2020) DOI: 10.1177/0271678X18806640

P-glycoprotein (P-gp, ABCB1) is an efflux transporter at the blood–brain barrier (BBB), which mediates clearance of beta-amyloid (Aβ) from brain into blood. We used (R)-[11C]verapamil PET in combination with partial P-gp inhibition with tariquidar to measure cerebral P-gp function in a beta-amyloidosis mouse model (APPtg) and in control mice at three different ages (50, 200 and 380 days). Following tariquidar pre-treatment (4 mg/kg), whole brain-to-plasma radioactivity concentration ratios (Kp,brain) were significantly higher in APPtg than in wild-type mice aged 50 days, pointing to decreased cerebral P-gp function. Moreover, we found an age-dependent decrease in cerebral P-gp function in both wild-type and APPtg mice of up to −50%. Alterations in P-gp function were more pronounced in Aβ-rich brain regions (hippocampus, cortex) than in a control region with negligible Aβ load (cerebellum). PET results were confirmed by immunohistochemical staining of P-gp in brain microvessels. Our results confirm previous findings of reduced P-gp function in Alzheimer’s disease mouse models and show that our PET protocol possesses adequate sensitivity to measure these functional changes in vivo. Our PET protocol may find use in clinical studies to test the efficacy of drugs to induce P-gp function at the human BBB to enhance Aβ clearance.
Publikation

Tchatchouang Noulala, C. G.; Fotso, G. W.; Rennert, R.; Lenta, B. N.; Sewald, N.; Arnold, N.; Happi, E. N.; Ngadjui, B. T.; Mesomeric form of quaternary indoloquinazoline alkaloid and other constituents from the Cameroonian Rutaceae Araliopsis soyauxii Engl. Biochem. Syst. Ecol. 91, 104050, (2020) DOI: 10.1016/j.bse.2020.104050

A mesomeric form of quaternary indoloquinazoline alkaloid, soyauxinium chloride (1) was obtained through the chemical investigation of stem bark and roots of Araliopsis soyauxii Engl. [syn. Vepris soyauxii (Engl.) Mziray] (Rutaceae) together with fifteen known compounds, including three furoquinoline alkaloids, three 2-quinolones, two limonoids, two triterpenes, two steroids, a coumarin, an acridone alkaloid, and a flavonoid glycoside. Their structures were established by comprehensive spectroscopic and spectrometric analyses (1D and 2D NMR, ESI-HR-MS) and by comparison with previously reported data. 13C NMR data of araliopsinine are also reported here for the first time. The isolated compounds were screened in vitro for their effects on the viability of two different human cancer cell lines, namely prostate PC-3 adenocarcinoma cells and colorectal HT-29 adenocarcinoma cells. However, none of the tested compounds exhibited strong anti-proliferative or cytotoxic activities, to either prostate PC-3 cells or colon HT-29 cells. At 100 μM, the furoquinoline maculine showed a slightly increased anti-proliferative effect, however, exclusively on HT-29 cells. The chemotaxonomic significance of the isolated compounds has also been discussed.

Diese Seite wurde zuletzt am 11.02.2013 geändert.

  • Die Leibniz-Gemeinschaft
  • Digitalisierung in der Landwirtschaft
  • Martin-Luther Universität Halle
IPB Mainnav Search