Person: ŞENKARDEŞ, İSMAİL
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ŞENKARDEŞ
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İSMAİL
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Publication Metadata only Multidirectional biological investigation and phytochemical profile of Rubus sanctus and Rubus ibericus(PERGAMON-ELSEVIER SCIENCE LTD, 2019) ŞENKARDEŞ, İSMAİL; Zengin, Gokhan; Ferrante, Claudio; Senkardes, Ismail; Gevrenova, Reneta; Zheleva-Dimitrova, Dimitrina; Menghini, Luigi; Orlando, Giustino; Recinella, Lucia; Chiavaroli, Annalisa; Leone, Sheila; Brunetti, Luigi; Picot-Allain, Carene Marie Nancy; Rengasamy, Kannan R. R.; Mahomoodally, Mohamad FawziIn the present study, the biological properties, including, the enzyme inhibitory and antioxidant activities, as well as, the phytochemical profile of the ethyl acetate, methanol, and water extracts of Rubus sanctus Schreb. and Rubus ibericus Juz. leaves were determined using in vitro bioassays. Wide range of phytochemicals, including, hydroxybenzoic acids, hydroxycinnamic acids, acylquinic acids, ellagitannins, flavonoids, and triterpenoid saponins were determined using UHPLC-ESI/HRMS technique. The ethyl acetate and methanol extracts of the studied Rubus species effectively inhibited acetyl and butyryl cholinesterase. On the other hand, R. sanctus water extract showed low inhibition against alpha-amylase and prominent inhibitory action against alpha-glucosidase. Data collected from this study reported the radical scavenging and reducing potential of the studied Rubus species. Investigation of the protective effects of the different extracts of R. sanctus and R. ibericus in experimental model of ulcerative colitis was performed. The extracts were also tested on spontaneous migration of human colon cancer cells (HCT116) in wound healing experimental paradigm. Only R. sanctus methanol extract inhibited spontaneous HCT116 migration in the wound healing test. Our results suggested that R. sanctus and R. ibericus may be potential candidates as sources of biologically-active compounds for the development of nutraceuticals, pharmaceuticals, and/or cosmetics.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 Untargeted metabolomic profiling of three Crataegus species (hawthorn) and their in vitro biological activities(WILEY, 2020) ŞENKARDEŞ, İSMAİL; Rocchetti, Gabriele; Senizza, Biancamaria; Zengin, Gokhan; Mahomodally, Mohamad Fawzi; Senkardes, Ismail; Lobine, Devina; Lucini, LuigiBACKGROUND In this investigation, the chemical and biological profiles of three Turkish Crataegus species (Crataegus orientalis, Crataegus szovitsii and Crataegus tanacetifolia) were studied in order to provide the first comprehensive characterization and their health-promoting potential. In this respect, polyphenolic profiles were evaluated using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. The in vitro antioxidant activities of the Crataegus samples were evaluated by using free-radical scavenging, phosphomolybdenum, ferrous-ion chelating, and reducing power assays. The inhibitory activities against alpha-glucosidase, amylase, cholinesterases (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)), and tyrosinase were also established. RESULTS The untargeted metabolomic approach highlighted the effect of both extraction types and species on the phenolic profiles of different Crateagus tissues (i.e. leaves and twigs). The methanolic extracts showed the maximum radical scavenging and reducing activity in all test systems, whereas for ferrous-ion chelating assays the decocted and infused extracts showed the highest activity. Only the methanolic extracts were effective against AChE and BChE. The extract tested showed remarkable inhibitory effects against tyrosinase and alpha-glucosidase, whereas all the extracts exhibited modest inhibition against alpha-amylase. Overall, the twig extracts of the three species studied showed superior antioxidant and enzyme inhibitory activities. CONCLUSION On the basis of these results, the three Crataegus species can be classified as potent bioresources for high-value phytochemicals, which warrant further investigations for developing novel nutraceuticals. (c) 2019 Society of Chemical IndustryPublication 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 UHPLC-QTOF-MS phytochemical profiling and in vitro biological properties of Rhamnus petiolaris (Rhamnaceae)(ELSEVIER, 2019) ŞENKARDEŞ, İSMAİL; Rocchetti, Gabriele; Miras-Moreno, Maria Begona; Zengin, Gokhan; Senkardes, Ismail; Sadeer, Nabeelah Bibi; Mahomoodally, Mohamad Fawzi; Lucini, LuigiThe genus Rhanmus has a great attention as source of bioactive compounds. So, this work aimed to investigate phytochemical profile and biological activity of water and methanolic extracts of different parts of Rhamnus petiolaris Boiss. & Balansa, namely twigs, leaves, mature and unmature fruits. The in vitro antioxidant activity, enzyme inhibitory properties, along with their polyphenol and anthraquinone profiles were determined by untargeted metabolomics. Results showed that methanolic and aqueous unmature fruit extracts were the most effective 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) scavenger (470.96 mg trolox equivalent (TE)/g and 394.96 mg TE/g, respectively). The aqueous unmature fruit extract displayed the most potent cupric and ferric reducing power and showed the highest total phenolic contents (TPC) (137.17 mg gallic acid equivalent (GAE)/g). The methanolic twig extract showed the highest enzymatic inhibitory property against of alpha-glucosidase, tyrosinase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). On the basis of the correlation coefficients calculated separately for all experimental parameter pairs, flavonols and anthocyanins highly correlated with DPPH, whereas tyrosols correlated with BChE activity. Multivariate statistics following untargeted metabolomics allowed to describe the differences in polyphenols and anthraquinones, as affected by the extraction solvent used. Mature and unmature fruits were substantially comparable and were affected in a similar way by the extraction conditions, while different profiles were recorded for Rhamnus leaves and twigs. These findings indicate that the recovery efficiencies of specific subclasses of compounds (above all when considering flavonoids, phenolic acids and anthraquinones) as a function of the matrix and extraction chosen, significantly affect the phytochemical profile and biological activity of Rhamnus.Publication Open Access Phytochemical Constituents and Biological Activities of the Unexplored Plant Rhinanthus angustifolius subsp. grandiflorus(MDPI, 2021-10-01) ŞENKARDEŞ, İSMAİL; Zhang, Leilei; Zengin, Gokhan; Rocchetti, Gabriele; Senkardes, Ismail; Sharmeen, Jugreet B.; Mahomoodally, Mohamad Fawzi; Behl, Tapan; Rouphael, Youssef; Lucini, LuigiIn the present study, a total of 12 extracts of Rhinanthus angustifolius subsp. grandiflorus, an understudied hemiparasitic species, were obtained using different extraction techniques, namely, homogenizer-assisted extraction (HAE), maceration (MAC), soxhlet (SOX), infusion, and solvents (ethyl acetate, methanol, ethanol, and water), and were evaluated for their in vitro antioxidant and enzyme-inhibiting properties. Additionally, untargeted profiling based on high-resolution mass spectrometry targeted different phytochemical classes, namely, polyphenols, terpenoids, and alkaloids. The highest total phenolic and flavonoid contents were detected using methanol as the extraction solvent. Multivariate statistics following the untargeted profiling revealed that the extraction solvent had a hierarchically higher impact than the extraction method when considering the recovery of bioactive compounds. The methanolic extracts displayed the highest radical-scavenging antioxidant capacity, as provided by CUPRAC and FRAP assays. On the other hand, the water extracts (MAC and HAE) and the infusion extract showed the highest activity as metal chelators (25.66-27.51 mg EDTAE/g). Similarly, the water extract obtained by HAE and the infusion extract revealed the highest phosphomolybdenum activity (3.92 & PLUSMN; 0.14 and 3.71 & PLUSMN; 0.01 mmol TE/g, respectively). The different extracts also exhibited different enzyme inhibition potentials. For instance, HAE and MAC ethanolic extracts inhibited only alpha-amylase (0.69 & PLUSMN; 0.01 and 0.70 & PLUSMN; 0.01 mmol ACAE/g), while all the other extracts showed a dual inhibition against both carbohydrate-hydrolyzing enzymes tested (i.e., alpha-amylase: 0.07-0.69 mmol ACAE/g; alpha-glucosidase: 0.03-1.30 mmol ACAE/g). Nevertheless, the other extracts inhibited acetyl-, butyryl-cholinesterases, or both; MAC-water extract displayed no inhibition against the enzymes. Additionally, all the studied extracts were found to inhibit tyrosinase, ranging from 10.62 to 52.80 mg KAE/g. In general, the water extracts showed weaker inhibition towards the enzymes than the other extracts. This study demonstrated that R. angustifolius is an excellent source of natural antioxidants and enzyme inhibitors that could be further investigated and exploited for pharmaceutical purposes.Publication Metadata only New insights into the in vitro biological effects, in silico docking and chemical profile of clary sage - Salvia sclarea L.(ELSEVIER SCI LTD, 2018) DOĞAN, AHMET; Zengin, Gokhan; Senkardes, Ismail; Mollica, Adriano; Picot-Allain, Carene Marie Nancy; Bulut, Gizem; Dogan, Ahmet; Mahomoodally, M. FawziSalvia sclarea L. is traditionally used to manage common human ailments and is consumed as a food product. This study aimed to establish the phytochemical profile and antioxidant potential of ethyl acetate, methanol, and water extracts of Salvia sclarea. The inhibitory action of the extracts against alpha-amylase, alpha-glucosidase, acetyicholinesterase, butyrylcholinesterase, and tyrosinase was also investigated. Methanol extract showed the highest phenolic and fiavonoid contents (81.78 mg GAE/g extract and 40.59 mg RE/g extract, respectively). Reversed phase high performance liquid chromatography with diode array detector analysis revealed that S. sclarea was rich in rosmarinic acid. The water extract exhibited the lowest inhibitory activity against alpha-amylase but the upmost activity against alpha-glucosidase (0.19 and 18.24 mmol ACAE/g extract, respectively). Experimental data showed that only the water extract (8.86 mg KAE/g extract) significantly inhibited tyrosinase. Docking studies showed that quercetin binds to tyrosinase by two hydrogen and a pi-pi bonds. Salvia sclarea showed interesting biological activity against key enzymes involved in the pathogenesis of common ailments. (C) 2018 Elsevier Ltd. All rights reserved.Publication Open Access Qualitative Fingerprint Analysis and Multidirectional Assessment of Different Crude Extracts and Essential Oil from Wild Artemisia santonicum L.(MDPI, 2019-08-07) ŞENKARDEŞ, İSMAİL; Ferrante, Claudio; Zengin, Gokhan; Menghini, Luigi; Diuzheva, Alina; Jeko, Jozsef; Cziaky, Zoltan; Recinella, Lucia; Chiavaroli, Annalisa; Leone, Sheila; Brunetti, Luigi; Lobine, Devina; Senkardes, Ismail; Mahomoodally, Mohamad Fawzi; Orlando, GiustinoArtemisia species are used as folk medicines in several countries. This work was aimed to shed more light on the effect of methanol, water, ethyl acetate extracts, and essential oil (EO) of A. santonicum on selected enzymes (cholinesterase, tyrosinase alpha-amylase, and alpha-glucosidase) as well of their antioxidant and pharmacological effects. The chemical profile of the essential oil was determined using gas chromatography coupled to mass spectrometry (GC-MS) analysis, while the extracts were chemically characterized by high performance liquid chromatography coupled to mass spectrometry (HPLC-MS). Forty-nine constituents were identified and camphor (36.6%), 1,8-cineole (10.2%), alpha-thujone (10.1%), borneol (4.5%), and beta-thujone (3.6%) were the major components. Overall, 45, 74, and 67 components were identified from the ethyl acetate, methanol, and water extracts, respectively. The EO and extracts showed significant antioxidant properties, in a cell-free model; particularly, methanol and water extracts revealed promising sources of antioxidant compounds. Additionally, we evaluated protective effects of EO and extracts in isolated rat colon tissue challenged with lipopolysaccharide (LPS), as an ex vivo model of colon inflammation, and human colon cancer HCT116 cell line. Particularly, we observed that, among all tested samples, A. santonicum ethyl acetate displayed the best pharmacological profile, being able to blunt LPS-induced levels of all tested biomarkers of inflammation and oxidative stress, including colon nitrites, lactate dehydrogenase, prostaglandin E-2, and serotonin. Additionally, this extract was also able to reduce HCT116 cell viability, thus suggesting potential antiproliferative effects against colon cancer cells. Based on our results, A. santonicum has great potential for developing novel functional agents including pharmaceuticals, cosmeceuticals, and nutraceuticals.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