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  1. Article ; Online: Astragalus Saponins, Astragaloside VII and Newly Synthesized Derivatives, Induce Dendritic Cell Maturation and T Cell Activation

    Nilgun Yakubogullari / Ali Cagir / Erdal Bedir / Duygu Sag

    Vaccines, Vol 11, Iss 495, p

    2023  Volume 495

    Abstract: Astragaloside VII (AST VII), a triterpenic saponin isolated from Astragalus species, shows promise as a vaccine adjuvant, as it supported a balanced Th1/Th2 immune response in previous in vivo studies. However, the underlying mechanisms of its adjuvant ... ...

    Abstract Astragaloside VII (AST VII), a triterpenic saponin isolated from Astragalus species, shows promise as a vaccine adjuvant, as it supported a balanced Th1/Th2 immune response in previous in vivo studies. However, the underlying mechanisms of its adjuvant activity have not been defined. Here, we investigated the impact of AST VII and its newly synthesized semi-synthetic analogs on human whole blood cells, as well as on mouse bone marrow-derived dendritic cells (BMDCs). Cells were stimulated with AST VII and its derivatives in the presence or absence of LPS or PMA/ionomycin and the secretion of cytokines and the expression of activation markers were analyzed using ELISA and flow cytometry, respectively. AST VII and its analogs increased the production of IL-1β in PMA/ionomycin-stimulated human whole blood cells. In LPS-treated mouse BMDCs, AST VII increased the production of IL-1β and IL-12, and the expression of MHC II, CD86, and CD80. In mixed leukocyte reaction, AST VII and derivatives increased the expression of the activation marker CD44 on mouse CD4 + and CD8 + T cells. In conclusion, AST VII and its derivatives strengthen pro-inflammatory responses and support dendritic cell maturation and T cell activation in vitro. Our results provide insights into the mechanisms of the adjuvant activities of AST VII and its analogs, which will be instrumental to improve their utility as a vaccine adjuvant.
    Keywords vaccine adjuvant ; triterpenoid saponin ; semi-synthesis ; immunomodulation ; immunological evaluation ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2023-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Neuroprotective metabolites via fungal biotransformation of a novel sapogenin, cyclocephagenol

    Melis Küçüksolak / Göklem Üner / Petek Ballar Kırmızıbayrak / Erdal Bedir

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 15

    Abstract: Abstract Cyclocephagenol (1), a novel cycloartane-type sapogenin with tetrahydropyran unit, is only encountered in Astragalus species. This rare sapogenin has never been a topic of biological activity or modification studies. The objectives of this study ...

    Abstract Abstract Cyclocephagenol (1), a novel cycloartane-type sapogenin with tetrahydropyran unit, is only encountered in Astragalus species. This rare sapogenin has never been a topic of biological activity or modification studies. The objectives of this study were; (i) to perform microbial transformation studies on cyclocephagenol (1) using Astragalus endophyte, Alternaria eureka 1E1BL1, followed by isolation and structural characterization of the metabolites; (ii) to investigate neuroprotective activities of the metabolites; (iii) to understand structure–activity relationships towards neuroprotection. The microbial transformation of cyclocephagenol (1) using Alternaria eureka resulted in the production of twenty-one (2–22) previously undescribed metabolites. Oxidation, monooxygenation, dehydration, methyl migration, epoxidation, and ring expansion reactions were observed on the triterpenoid skeleton. Structures of the compounds were established by 1D-, 2D-NMR, and HR-MS analyses. The neuroprotective activities of metabolites and parent compound (1) were evaluated against H2O2-induced cell injury. The structure–activity relationship (SAR) was established, and the results revealed that 1 and several other metabolites had potent neuroprotective activity. Further studies revealed that selected compounds reduced the amount of ROS and preserved the integrity of the mitochondrial membrane. This is the first report of microbial transformation of cyclocephagenol (1).
    Keywords Medicine ; R ; Science ; Q
    Subject code 500
    Language English
    Publishing date 2022-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: New Cardenolides from Biotransformation of Gitoxigenin by the Endophytic Fungus Alternaria eureka 1E1BL1

    Erdal Bedir / Çiğdem Karakoyun / Gamze Doğan / Gülten Kuru / Melis Küçüksolak / Hasan Yusufoğlu

    Molecules, Vol 26, Iss 3030, p

    Characterization and Cytotoxic Activities

    2021  Volume 3030

    Abstract: Microbial biotransformation is an important tool in drug discovery and for metabolism studies. To expand our bioactive natural product library via modification and to identify possible mammalian metabolites, a cytotoxic cardenolide (gitoxigenin) was ... ...

    Abstract Microbial biotransformation is an important tool in drug discovery and for metabolism studies. To expand our bioactive natural product library via modification and to identify possible mammalian metabolites, a cytotoxic cardenolide (gitoxigenin) was biotransformed using the endophytic fungus Alternaria eureka 1E1BL1. Initially, oleandrin was isolated from the dried leaves of Nerium oleander L. and subjected to an acid-catalysed hydrolysis to obtain the substrate gitoxigenin (yield; ~25%). After 21 days of incubation, five new cardenolides 1 , 3 , 4 , 6 , and 8 and three previously- identified compounds 2 , 5 and 7 were isolated using chromatographic methods. Structural elucidations were accomplished through 1D/2D NMR, HR-ESI-MS and FT-IR analysis. A. eureka catalyzed oxygenation, oxidation, epimerization and dimethyl acetal formation reactions on the substrate. Cytotoxicity of the metabolites were evaluated using MTT cell viability method, whereas doxorubicin and oleandrin were used as positive controls. Biotransformation products displayed less cytotoxicity than the substrate. The new metabolite 8 exhibited the highest activity with IC 50 values of 8.25, 1.95 and 3.4 µM against A549, PANC-1 and MIA PaCa-2 cells, respectively, without causing toxicity on healthy cell lines (MRC-5 and HEK-293) up to concentration of 10 µM. Our results suggest that A. eureka is an effective biocatalyst for modifying cardenolide-type secondary metabolites.
    Keywords Nerium oleander L ; cardenolides ; oleandrin ; gitoxigenin ; biotransformation ; endophytic fungus ; Organic chemistry ; QD241-441
    Subject code 500
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: Ligand-based virtual screening and molecular docking of two cytotoxic compounds isolated from Papaver lacerum

    Bayazeid, Omer / Erdal Bedir / Funda N. Yalcin

    Phytochemical Society of Europe Phytochemistry letters. 2019 Apr., v. 30

    2019  

    Abstract: This study revealed that the Papaver lacerum extract strongly inhibited HeLa cell proliferation, resulting in 13% cell viability. As a result of phytochemical studies, one known compound, Tyrosol-1-O-β-xylopyranosyl-(1→6)-O-β-glucopyranoside) (I), and ... ...

    Abstract This study revealed that the Papaver lacerum extract strongly inhibited HeLa cell proliferation, resulting in 13% cell viability. As a result of phytochemical studies, one known compound, Tyrosol-1-O-β-xylopyranosyl-(1→6)-O-β-glucopyranoside) (I), and one new compound, 5-O-(6-O-α-rhamnopyronosyl-β-glucopyronosyl) mevalonic acid (II), were isolated. Compounds I and II were found to possess a moderate cytotoxic effect with an IC50 of 66.4 μM (p < 0.0001) and 54 μM (p < 0.0001), respectively. The ligand-based virtual screening technique was used to reveal the possible molecular target of compounds I and II. The molecular target was identified as protein-tyrosine kinase Syk for compound I, and aldo-keto reductase family-1 for compound II. Molecular docking was used to assess the binding affinity of the compounds with the targets obtained from ligand-based virtual screening.
    Keywords alcohol oxidoreductases ; binding capacity ; cell proliferation ; cell viability ; chemical constituents of plants ; computer simulation ; cytotoxicity ; human cell lines ; inhibitory concentration 50 ; mevalonic acid ; Papaver ; receptor protein-tyrosine kinase ; screening
    Language English
    Dates of publication 2019-04
    Size p. 26-30.
    Publishing place Elsevier Ltd
    Document type Article
    ISSN 1874-3900
    DOI 10.1016/j.phytol.2019.01.007
    Database NAL-Catalogue (AGRICOLA)

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  5. Article: Biotransformation of cyclocanthogenol by the endophytic fungus Alternaria eureka 1E1BL1

    Ekiz, Güner / Erdal Bedir / Seda Duman

    Phytochemistry. 2018 July, v. 151

    2018  

    Abstract: The microbial transformation of cyclocanthogenol (CCG), Astragalus sp. originated sapogenin, by the endophytic fungus Alternaria eureka 1E1BL1 isolated from Astragalus angustifolius was investigated. Hydroxylation, oxidation, epoxidation, O-methylation, ... ...

    Abstract The microbial transformation of cyclocanthogenol (CCG), Astragalus sp. originated sapogenin, by the endophytic fungus Alternaria eureka 1E1BL1 isolated from Astragalus angustifolius was investigated. Hydroxylation, oxidation, epoxidation, O-methylation, ring-expansion and methyl migration reactions were observed on the triterpenoid skeleton. As a result, eight metabolites were isolated and the structures of the previously undescribed compounds were established by 1-D, 2-D NMR and HR-MS analyses.
    Keywords Alternaria ; Astragalus ; biotransformation ; endophytes ; epoxidation reactions ; fungi ; hydroxylation ; metabolites ; nuclear magnetic resonance spectroscopy ; oxidation ; triterpenoids
    Language English
    Dates of publication 2018-07
    Size p. 91-98.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 208884-8
    ISSN 1873-3700 ; 0031-9422
    ISSN (online) 1873-3700
    ISSN 0031-9422
    DOI 10.1016/j.phytochem.2018.04.006
    Database NAL-Catalogue (AGRICOLA)

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  6. Article: Specialized metabolites from the aerial parts of Centaurea polyclada DC

    Demir, Serdar / Canan Karaalp / Erdal Bedir

    Phytochemistry. 2017 Nov., v. 143

    2017  

    Abstract: The genus Centaurea L. (Asteraceae) is represented by 200 taxa in the flora of Turkey and several Centaurea species are used as herbal remedies against different conditions. Previous phytochemical investigations on this genus generally revealed the ... ...

    Abstract The genus Centaurea L. (Asteraceae) is represented by 200 taxa in the flora of Turkey and several Centaurea species are used as herbal remedies against different conditions. Previous phytochemical investigations on this genus generally revealed the isolation of sesquiterpene lactones and flavonoid derivatives. In our continuous search on Centaurea genus, a phytochemical study was performed on Centaurea polyclada DC., an endemic of West Anatolia.Previously undescribed two sesquiterpene-amino acid conjugates, an elemane and an eudesmane derivative were isolated from the aerial parts of Centaurea polyclada, together with eight known compounds; two elemane derivatives, three flavonoids, a lignan, a phenolic glucoside and a phenylpropanoid glucoside. Structural elucidation of the compounds was based on spectroscopic evidence, including 1D and 2D NMR and high-resolution mass spectrometry, chemical degradation results and reference data comparison. Sesquiterpene-amino acid conjugates are representatives of an unusual group of sesquiterpenes, and elemane-amino acid conjugates are herein reported for the first time in nature.
    Keywords aerial parts ; Centaurea ; chemical degradation ; flavonoids ; flora ; glucosides ; lignans ; mass spectrometry ; metabolites ; nuclear magnetic resonance spectroscopy ; sesquiterpenoid lactones ; spectral analysis ; Turkey (country)
    Language English
    Dates of publication 2017-11
    Size p. 12-18.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 208884-8
    ISSN 1873-3700 ; 0031-9422
    ISSN (online) 1873-3700
    ISSN 0031-9422
    DOI 10.1016/j.phytochem.2017.07.002
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: A New Siderophore from Sponge Associated Pseudomonas fluorescens 4.9.3

    F. Can Özkaya / Erdal Bedir / E. Esin Hameş

    Records of Natural Products, Vol 9, Iss 4, Pp 509-

    2015  Volume 517

    Abstract: In this study, Pseudomonas fluorescens 4.9.3 isolated from a sponge sample was investigated for its secondary metabolites. Two metabolites were isolated, and their structures were elucidated by 1D-, 2D NMR and LC-MS/MS experiments. The new compound (1) ... ...

    Abstract In this study, Pseudomonas fluorescens 4.9.3 isolated from a sponge sample was investigated for its secondary metabolites. Two metabolites were isolated, and their structures were elucidated by 1D-, 2D NMR and LC-MS/MS experiments. The new compound (1) was established as (5R)-N-(2-(1H-imidazol-4-yl)ethyl)-2-(2-hydroxyphenyl)-5-methyl-4,5-dihydrooxazole-4-carboxamide, while the known metabolite was determined as pre-pseudomonine.
    Keywords Pseudomonas fluorescens ; siderophore ; pseudomonine ; Chemistry ; QD1-999 ; Organic chemistry ; QD241-441 ; Botany ; QK1-989
    Language English
    Publishing date 2015-06-01T00:00:00Z
    Publisher ACG Publications
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: Unusual sesquiterpenes from Centaurea athoa DC

    Demir, Serdar / Canan Karaalp / Erdal Bedir

    Phytochemistry letters. 2016 Mar., v. 15

    2016  

    Abstract: Three new elemane-type sesquiterpenes; athoin, 14-O-acetylathoin and methyl 14-O-acetylathoin-12-oate were isolated from the aerial parts of Centaurea athoa DC., accompanying with eight known compounds: a germacrane-type sesquiterpene; 4'- ... ...

    Abstract Three new elemane-type sesquiterpenes; athoin, 14-O-acetylathoin and methyl 14-O-acetylathoin-12-oate were isolated from the aerial parts of Centaurea athoa DC., accompanying with eight known compounds: a germacrane-type sesquiterpene; 4'-hydroxypecterolide-14-O-acetate, three phenolic compounds; p-hydroxybenzoic acid, protocatechuic acid, vanillic acid-4-O-β-d-glucopyranoside methyl ester, an acetophenon glucoside; picein, two phenylpropane glucosides; syringin and 9-O-methyl coniferin, and a phytosterol; β-sitosterol-3-O-β-d-glucopyranoside. Structural elucidation of the compounds was based on both spectroscopic evidence and reference data comparison.
    Keywords 4-hydroxybenzoic acid ; aerial parts ; Centaurea ; glucosides ; phytosterols ; protocatechuic acid ; sesquiterpenoids ; spectral analysis
    Language English
    Dates of publication 2016-03
    Size p. 245-250.
    Publishing place Elsevier Ltd
    Document type Article
    ISSN 1874-3900
    DOI 10.1016/j.phytol.2016.02.012
    Database NAL-Catalogue (AGRICOLA)

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  9. Article: Biotransformation of Neoruscogenin by the Endophytic Fungus Alternaria eureka

    Özçınar, Özge / Bijen Kivçak / Erdal Bedir / Hasan Yusufoglu / Özgür Tağ

    Journal of natural products. 2018 June 12, v. 81, no. 6

    2018  

    Abstract: Biotransformation of neoruscogenin (NR, 1, spirosta-5,25(27)-diene-1β,3β-diol), the major bioactive sapogenin of Ruscus preparations, was carried out with the endophytic fungus Alternaria eureka. Fourteen new biotransformation products (2–15) were ... ...

    Abstract Biotransformation of neoruscogenin (NR, 1, spirosta-5,25(27)-diene-1β,3β-diol), the major bioactive sapogenin of Ruscus preparations, was carried out with the endophytic fungus Alternaria eureka. Fourteen new biotransformation products (2–15) were isolated, and their structures were elucidated by NMR and HRESIMS data analyses. A. eureka affected mainly oxygenation, oxidation, and epoxidation reactions on the B and C rings of the sapogenin to afford compounds 8–15. In addition to these, cleavage of the spiroketal system as in compounds 2–7 and subsequent transformations provided unusual metabolites. This is the first study reporting conversion of the spirostanol skeleton to cholestane-type metabolites 2–5. Additionally, the cleavage of the C-22/C-26 oxygen bridge yielding a furostanol-type steroidal framework and subsequent formation of the epoxy bridge between C-18 and C-22 in 7 was encountered for the first time in steroid chemistry.
    Keywords Alternaria ; biotransformation ; endophytes ; epoxidation reactions ; epoxides ; fungi ; mass spectrometry ; metabolites ; nuclear magnetic resonance spectroscopy ; oxidation ; oxygen ; Ruscus
    Language English
    Dates of publication 2018-0612
    Size p. 1357-1367.
    Publishing place American Chemical Society and American Society of Pharmacognosy
    Document type Article
    ZDB-ID 304325-3
    ISSN 1520-6025 ; 0163-3864
    ISSN (online) 1520-6025
    ISSN 0163-3864
    DOI 10.1021/acs.jnatprod.7b00898
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Astragaloside IV and Cycloastragenol Production Capacity of Astragalus trojanus Calli

    Pinar Nartop / Aynur Gurel / Ismail Hakki Akgun / Erdal Bedir

    Records of Natural Products, Vol 9, Iss 1, Pp 49-

    2015  Volume 61

    Abstract: Astragalus species are medicinal plants which produce valuable secondary metabolites, especially cycloartane-type glycosides. In this study, stem and leaf explants of Astragalus trojanus were subjected to different plant growth regulators, environmental ... ...

    Abstract Astragalus species are medicinal plants which produce valuable secondary metabolites, especially cycloartane-type glycosides. In this study, stem and leaf explants of Astragalus trojanus were subjected to different plant growth regulators, environmental conditions and media compositionsto identify their callus responses. Stem and leaf explants were cultured in Murashige and Skoog (MS) and woody plant (WPM) media supplemented with different concentrations of kinetin, naphthalene acetic acid, 2,4-dichlorophenoxyacetic acid, thidiazurone and indole acetic acid under two light intensities (1000 and 4000 lux) and also in dark conditions. Both MS and WPM media triggered callus regeneration. Although, callus regeneration was observed on both stem and leaf explants, callus biomass accumulation on stem explants were higher. Addition of 100 μg/L selenium and doubled concentration of WPM vitamins enhanced callus biomass on stem explants under dark conditions. Stem explants also regenerated shoots at high frequencies (up to 93%), especially in kinetin added media. Astragaloside IV and cycloastragenol accumulation efficiencies were determined in calli tissues. The highest astragaloside IV production (3.5 µg/mg) was found in callus tissue regenerated from stem explants in D1 medium, whereas the highest cycloastragenol accumulation (4.8 µg/mg) was detected in callus tissue regenerated from stem explants in N2 medium.
    Keywords Astragalus trojanus ; callus ; shoot regeneration ; astragaloside IV ; cycloastragenol ; plant growth regulators ; Chemistry ; QD1-999 ; Organic chemistry ; QD241-441 ; Botany ; QK1-989
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher ACG Publications
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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