Person: ŞENKARDEŞ, İSMAİL
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ŞENKARDEŞ
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İSMAİL
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Publication Metadata only Utilisation of Rhododendron luteum Sweet bioactive compounds as valuable source of enzymes inhibitors, antioxidant, and anticancer agents(PERGAMON-ELSEVIER SCIENCE LTD, 2020) ŞENKARDEŞ, İSMAİL; Mahomoodally, Mohamad Fawzi; Sieniawska, Elwira; Sinan, Kouadio Ibrahime; Picot-Allain, Marie Carene Nancy; Yerlikaya, Serife; Baloglu, Mehmet Cengiz; Altunoglu, Yasemin Celik; Senkardes, Ismail; Rengasamy, Kannan R. R.; Zengin, GokhanEthnobotanical evidences report the use of Rhododendron luteum Sweet (Ericaceae) in traditional medicinal systems. However, R. luteum has been associated to the occurrence of 'mad honey' poisoning. In the present study, the ethyl acetate, methanol, and water extracts of R. luteum were investigated for their in vitro antioxidant, enzyme inhibition, and cytotoxic properties. The cytotoxicity of R. luteum extracts on A549 lung cancer cell line was evaluated using MTT cell viability assay. Besides, HPLC-ESI-MSn approach was employed to elucidate the secondary metabolite profiles of R. luteum in order to establish any structure-activity relationship. Methanol and water extracts of R. luteum possessed highest radical scavenging and reducing properties while the ethyl acetate extract showed highest metal chelating properties. In terms of enzyme inhibition, the methanol and ethyl acetate extracts of R. luteum, possessing epigallocatechin, were active inhibitors of cholinesterase enzymes, a-glucosidase, and tyrosinase. Water extract caused growth inhibition of A549 cells with 207.2 mu g/ml IC50 value. Though R. luteum has received little scientific attention due to the occurrence of grayanotoxins in the plant, however, data presented in this work shows promising biological activity of R. luteum and highlighted its role as a potential source of antioxidant and key enzyme inhibitors.Publication Metadata only Metabolomics-based profiling with chemometric approach to delineate the bio-pharmaceutical properties of fruit extracts from Ligustrum vulgare L(ELSEVIER, 2019) ŞENKARDEŞ, İSMAİL; Rocchetti, Gabriele; Senizza, Biancamaria; Zengin, Gokhan; Senkardes, Ismail; Sadeer, Nabeelah Bibi; Mahomoodally, Mohamad Fawzi; Lucini, LuigiLigustrum vulgare L. (Family: Oleaceae) is an evergreen shrub native to North-west Africa, Europe and Western Asia. In the present work, infusion (water), ethyl acetate, methanol and n-hexane extracts of the fruits of L. vulgare L. were studied for their in vitro antioxidant and enzyme inhibitory properties along with their untargeted polyphenolic profile (using an ultra-high-performance liquid chromatography-quadrupole time-of-flight (UHPLC-QTOF) mass spectrometry approach). Untargeted metabolomics coupled to multivariate statistics showed that Ligustrum fruit extracts were very abundant in polyphenols, such as flavonoids, tyrosols and lignans, with ethyl acetate allowing the highest recovery among the extraction solvents tested. The methanolic extract inhibited the highest acetylcholinesterase (AChE), tyrosinase and glucosidase activity (4.23 mg galatamine equivalent (GALAE)/g, 132.85 mg kojic acid equivalent (KAE)/g and 1.94 mmol acarbose equivalent (ACAE)/g respectively) while the ethyl acetate extract inhibited the highest butyrylcholinesterase (BChE) and amylase activity (4.92 mg GALAE/g and 0.73 mmol ACAE/g, respectively). However, the infusion showed the weakest activity against all the enzymes studied. However, the extract showed highest antioxidant property in'the antioxidant assays (except for phosphomolybdenum). The present paper is the first comprehensive report on L. vulgare fruits and thus our findings are of considerable interest to design new bioproducts for the pharmaceutical and cosmeceutical industry in the future.Publication Metadata only Chemical profiles and biological potential of tuber extracts from Cyclamen coum Mill(ELSEVIER, 2021) ŞENKARDEŞ, İSMAİL; Mahomoodally, Mohamad Fawzi; Picot-Allain, Marie Carene Nancy; Zengin, Gokhan; Llorent-Martinez, Eulogio J.; Stefanucci, Azzurra; Gunes, Ak; Senkardes, Ismail; Tomczyk, Michal; Mollica, AdrianoCyclamen coum Mill. used in traditional medicine has been reported to exhibit interesting biological activities. In this study, the ability of the C. coum tuber extracts to inhibit clinical enzymes, namely, cholinesterases, ty-rosinase, alpha-amylase, and alpha-glucosidase, as well as the antioxidant properties were assessed. High -performance liquid chromatography/electrospray ionization quadrupole-time -of-flight mass spectrometer (HPLC- ESI-Q -TOF-MS) was employed to obtain detailed phytochemical proiles and in silico studies were performed against the key clinical enzymes. HPLC- ESI-Q -TOF -MS results conirmed the presence of saponins cyclacoumin and cy-claminorin, which were previously identiied from C. coum tuber extracts. In addition, other phenolic com-pounds, namely, phloretin C -dihexoside, quercetin 3 -galactoside, and catechin, were also identiied from C. coum tuber extracts. The methanol extract showed interesting inhibition against tyrosinase (6 5. 87 mg kojic acid equivalent/g extract) and alpha-glucosidase (3 4. 41 mg acarbose equivalent / g extract). Low inhibition was observed against cholinesterases and alpha-amylase. The methanol also showed active antioxidant properties (expressed as Trolox equivalent [TE]), namely, radical scavenging and reducing potential (1 5. 17 and 21 .8 6 mg TE / g extract, for 2, 2 '- azino- bis(3-ethylbenzthiazoline -6 -sulfonic acid) and cupric reducing antioxidant capacity assays, re-spectively). In order to highlight the possible bioactive compounds responsible of the biological effect, phloretin C -diglucoside, catechin and quercetin 3 -galactoside were docked via in silico molecular modelling ap-proaches. For tyrosinase, quercetin 3 -galactoside showed better docking and free binding energy which was found to bind very strongly to the enzymatic cavity of tyrosinase (via hydrogen bonds to Glu322, His85, His263, Gly281 and pi-pi stacks to His263 and His259). Findings from this study tend to advocate for further in-vestigations focusing on the isolation of bioactive compounds from the methanol extract of C. coum tuber ex-tracts and assessment of their cytotoxicity and their bioactivity.Publication Metadata only Antioxidant abilities, key enzyme inhibitory potential and phytochemical profile of Tanacetum poteriifolium Grierson(ELSEVIER, 2019) ŞENKARDEŞ, İSMAİL; Zengin, Gokhan; Sieniawska, Elwira; Senkardes, Ismail; Picot-Allain, Marie Carene Nancy; Sinan, Kouadio Ibrahime; Mahomoodally, Mohamad FawziThe members of the genus Tanacetum have a long history in traditional medicine to manage several diseases. Thus, the present study attempts to determine the chemical composition and to probe into the biological activities of Tanacetum poteriifolium Grierson, a poorly studied medicinal plant. The enzyme inhibitory and antioxidant properties of the ethyl acetate, methanol, and water extracts were assessed using standard in vitro assays. Biological data were further investigated by multivariate analysis tools. The water extract showed the highest concentration of phenolics (83.38 mg gallic acid equivalent (GAE)/g extract), and was a potent radical scavenger (238.12 and 282.54 mg Trolox equivalent (TE)/g extract, towards 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS), respectively) and had potent reducing power (555.03 and 285.79 mg TE/g extract, towards cupric reducing antioxidant capacity (CUPRAC) and ferric reducing antioxidant power (FRAP), respectively). The ethyl acetate extract (41.07 mg ethylenediaminetetraacetic acid equivalent (EDTAE)/g extract), rich in flavonoids (43.55 mg rutin equivalent (RE)/g extract), was a potent metal chelator. Besides, the ethyl acetate extract exhibited strong inhibitory action on cholinesterases (3.47 and 3.46 mg galantamine equivalent (GALAE)/g extract) and alpha-glucosidase (23.67 mmol acarbose equivalent (ACAE)/g extract). Tyrosinase was actively inhibited in the presence of the methanol extract of T. poteriifolium (128.54 mg kojic acid equivalent (KAE)/g extract). Liquid chromatography-electrospray ionisation quadrupole time-of-flight mass spectrometry analysis revealed the presence of quinic acid and methylquercetin derivatives in T. poteriifolium ethyl acetate extract. Two unknown compounds having m/z values 289.17, 267.23, 235.13, 211.14, 185.12, 121.06 and 275.21, 211.15, 171.11, 121.11 were identified from the T. poteriifolium methanol extract. Principal component analysis was performed to obtain an overview of the influence of solvents on T. poteriifolium biological activities which were satisfactorily discriminated. This study provides valuable baseline data on the biological activity of T. poteriifolium towards important enzymes targeted in the management of global health problems, such as Alzheimer's disease, diabetes, and epidermal hyperpigmentation problems.Publication Metadata only Tanacetum vulgare L. (Tansy) as an effective bioresource with promising pharmacological effects from natural arsenal(PERGAMON-ELSEVIER SCIENCE LTD, 2021) ŞENKARDEŞ, İSMAİL; Ak, Gunes; Gevrenova, Reneta; Sinan, Kouadio Ibrahime; Zengin, Gokhan; Zheleva, Dimitrina; Mahomoodally, Mohamad Fawzi; Senkardes, Ismail; Brunetti, Luigi; Leone, Sheila; Di Simone, Simonetta Cristina; Recinella, Lucia; Chiavaroli, Annalisa; Menghini, Luigi; Orlando, Giustino; Ferrante, ClaudioThe Tanacetum genus is a big treasure with the presence of biologically-active compounds and members of this genus are widely used for the treatment of several diseases in traditional medicine system. Considering this fact, we aimed to analyze the extracts from Tanacetum vulgare L. in case of chemical profiles and biological effects. Chemical characterization was performed by using UHPLC-HRMS technique and showed the presence of several phytochemical groups (107 compounds were identified, including phenolic acids, flavonoids, terpenoids and fatty acids. Biological abilities were examined by using antioxidant (DPPH, ABTS, FRAP, CUPRAC, metal chelating and phosphomolybdenum assays) and enzyme inhibition (tyrosinase, amylase, glucosidase and cholinesterase) properties. Pharmaco-toxicological investigations were also performed with the aim to identify limits of biocompatibility, anti-oxidant and neuromodulatory effects, in hypothalamic HypoE22 cells. A bio-informatic analysis was also carried to unravel the putative protein-targets for the observed biological effects. Generally, the tested hexane and hydroalcoholic extracts displayed stronger activities in antioxidant and enzyme inhibitory assays, when compared with water. In addition, multivariate analysis was performed to understand the differences in both solvents and plant parts and we clearly observed the separation of these parameters. The extracts (10 mu g/mL) also stimulated DAT and inhibited TNF alpha and BDNF gene expression, in HypoE22 cells. In parallel, the extracts were also able to stimulate norepinephrine release from this cell line. By contrast, in the concentration range 50-100 mu g/mL, the extracts reduced the HypoE22 viability, thus demonstrating cytotoxicity at concentrations 5-10 fold higher compared to those effective as neuromodulatory. Our observations manifested that T. vulgare has several beneficial effects and it can be used as a potential natural raw material for designing further health-promoting applications in nutraceutical, cosmeceutical, and pharmaceutical areas.Publication Metadata only Biologically active compounds from two members of the Asteraceae family: Tragopogon dubius Scop. and Tussilago farfara L.(TAYLOR & FRANCIS INC, 2019) DOĞAN, AHMET; Uysal, Sengul; Senkardes, Ismail; Mollica, Adriano; Zengin, Gokhan; Bulut, Gizem; Dogan, Ahmet; Glamoclija, Jasmina; Sokovic, Marina; Lobine, Devina; Mahomoodally, Fawzi M.Tragopogon dubius and Tussilago farfara are consumed as vegetables and used in folk medicine to manage common diseases. Herein, the chemical compositions and biological activities of different leaf extracts (ethyl acetate, methanol, and water) of T. dubius and T. farfara were evaluated. The antibacterial, antifungal, and antioxidant abilities of the extracts were tested using different assays including free radical scavenging, reducing power, phosphomolybdenum, and metal chelating assays. Enzyme inhibitory potentials were evaluated against cholinesterases, tyrosinase, alpha-amylase and alpha-glucosidase. Complexes of bioactive compounds (chlorogenic and rosmarinic acid) were docked into the enzymatic cavity of alpha-glucosidase and subjected to molecular dynamic calculation, enzyme conformational stability, and flexibility analysis. T. dubius and T. farfara extracts showed remarkable antioxidant potentials. Ethyl acetate extracts of T. dubius and T. farfara were the most potent inhibitors of acetylcholinesterase and butyrylcholinesterase. T. dubius ethyl acetate extract and T. farfara methanolic extract showed noteworthy activity against alpha-glucosidase. High performance liquid chromatography analysis revealed the abundance of some phenolic compounds including chlorogenic and rosmarinic acids. Ethyl acetate extract of T. dubius showed notable antifungal activity against all strains. Docking studies showed best pose for chlorogenic acid was stabilized by a network of hydrogen bonds with residues Asp1157, Asp1279, whereas rosmarinic acid showed several hydrogen bonds with Asp1157, Asp1420, Asp1526, Lys1460 and Trp1369. This study further validates the use of T. dubius and T. farfara in traditional medicine, as well as act as a stimulus for further studies for future biomedicine development. Communicated by Ramaswamy H. Sarma