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Öğe Anti-diabetic and anti-hyperlipidemic properties of Capparis spinosa L.: In vivo and in vitro evaluation of its nutraceutical potential(ELSEVIER SCIENCE BV, 2017) Mollica, Adriano; Zengin, Gökhan; Locatelli, Marcello; Stefanucci, Azzurra; Mocan, Andrei; Macedonio, Giorgia; Carradori, SimoneIn this study, the nutraceutical potential of Capparis spinosa L for the treatment of hyperglycemic states has been thoroughly investigated. A series of in vivo and in vitro tests have been conducted on fresh leaf, buds and salty buds (24 h desalted) processed to dry powder. 60% MeOH/H2O extracts were obtained for HPLC analysis and for alpha-amylase and alpha-glucosidase inhibition tests. To estimate the in vivo anti-diabetic effect, dry powders of C spinosa leaf and buds were orally administered to streptozocin-induced diabetic rats over a period of 28 days. At the end of the experiment, animals were sacrificed, blood taken for assessment of lipid profile and liver/kidney biochemistry while section of the pancreas, liver and kidneys were processed for general histology. Results showed that the regular administration of C. spinosa leaf or buds normalized all the biochemical parameters and reversed the liver/kidney injury with variable degrees of organ protection. (C) 2017 Elsevier Ltd. All rights reserved.Öğe Anti-oxidant and tyrosinase inhibitory in vitro activity of amino acids and small peptides: new hints for the multifaceted treatment of neurologic and metabolic disfunctions(MDPI, 2019) Luisi, Grazia; Stefanucci, Azzurra; Zengin, Gökhan; Dimmito, Marilisa Pia; Mollica, AdrianoOxidative damage is among the factors associated with the onset of chronic pathologies, such as neurodegenerative and metabolic diseases. Several classes of anti-oxidant compounds have been suggested as having a protective role against cellular stressors, but, in this perspective, peptides' world represents a poorly explored source. In the present study, the free radical scavenging properties, the metal ion reducing power, and the metal chelating activity of a series of sulfurated amino acids and tripeptides were determined in vitro through canonical assays (DPPH, ABTS, CUPRAC, FRAP, PM, and EECC) and estimated in comparison with the corresponding activities of synthetic peptide semicarbazones, incorporating the peculiar non-proteinogenic amino acid, tert-leucine (tLeu). The compounds exhibited remarkable anti-oxidant properties. As expected, sulfurated compounds 1-5 were found to be the most efficient radical scavengers and strongest reductants. Nevertheless, tLeu-containing peptides 7 and 8 disclosed notable metal reducing and chelating activities. These unprecedented results indicate that tLeu-featuring di- and tripeptide backbones, bearing the semicarbazone chelating moiety, are compatible with the emergence of an anti-oxidant potential. Additionally, when tested against a panel of enzymes usually targeted for therapeutic purposes in neurodegenerative and metabolic disorders, all samples were found to be good inhibitors of tyrosinase.Öğe Chemical characterization, antioxidant properties, anti-inflammatory activity, and enzyme inhibition of Ipomoea batatas L. leaf extracts(TAYLOR & FRANCIS INC, 2017) Zengin, Gökhan; Locatelli, Marcello; Stefanucci, Azzurra; Macedonio, Giorgia; Novellino, Ettore; Mirzaie, Sako; Dvoracsko, SzabolcsIpomoea batatas L. is widely used as a functional food in many countries. In this work, I. batatas leaf extracts (Soxhlet extract, microwave [MW] extract, and decoction extract) were characterized for the first time, and their total flavonoid and phenolic compound contents were measured by spectrophotometric and chromatographic analyses. These extracts were investigated for their antioxidant activities (free radical scavenging and reducing power assays), enzyme inhibitory activities (cholinesterase, tyrosinase, alpha-amylase, and alpha-glucosidase) and effects on inflammation pathways. Various bioactive secondary metabolites were identified; among them, chlorogenic acid appeared to be the most abundant. The decoction extract displayed the highest level of phenolics (89.26mg GAE/g extract) and thus exhibited stronger antioxidant ability than the Soxhlet and MW extracts. Each preparation was tested in in vitro enzymatic assays, which revealed that all three extracts exhibited interesting inhibitory activities against acetylcholinesterase, alpha-glucosidase, and alpha-amylase. Moreover, in vitro and ex vivo anti-inflammatory activities were observed for the decoction extract. Collectively, these results indicated that I. batatas leaf can be considered a potential candidate for the development of functional foods to combat the symptoms of metabolic disorders, such as type II diabetes mellitus.Öğe Chemical profile, antiproliferative, antioxidant, and enzyme inhibition activities and docking studies of Cymbopogon schoenanthus (L.) Spreng. and Cymbopogon nervatus (Hochst.) Chiov. from Sudan(WILEY, 2020) Yagi, Sakina; Mohammed, Atif B. A.; Tzanova, Tzvetomira; Schohn, Herve; Abdelgadir, Haider; Stefanucci, Azzurra; Mollica, Adriano; Zengin, GökhanEssential oils from the inflorescence of Cymbopogon schoenanthus and C. nervatus growing in Northern Sudan were examined for their chemical composition, antiproliferative activity against human breast carcinoma and human colon adenocarcinoma cell lines, antioxidant activity (phosphomolybdenum, antiradical, reducing power, and ferrous chelating), and enzyme inhibition activity against acetylcholinesterase butyrylcholinesterase, tyrosinase, alpha-glucosidase, and alpha-amylase. In silico study on the inhibition of tyrosinase and alpha-amylase was also performed. Piperitone (59.1%) and isomers of para-menthadienols (35.3%) were the main compounds in C. schoenanthus and C. nervatus oils, respectively. Oil from C. nervatus possessed higher antioxidant activity than that from C. schoenanthus except for its metal chelating ability. Both oils showed high antiproliferative activity. In silico study showed that trans-p-mentha-2,8-dien-1-ol and piperitone (both isomers) revealed the best docking scores for alpha-amylase and tyrosinase, respectively. In conclusion, oils from these two Cymbopogon species could be new natural agents with functional properties for food, cosmetics, and pharmaceutical industries. Practical applications Recently, there is a growing tendency to replace synthetic oils by natural ones in the cosmetic, food, and pharmaceutical products. In this context, we investigated the chemical characterization and biological activities of two Cymbopogon species essential oils (C. schoenanthus (L.) Spreng. and C. nervatus). Antioxidant capacity, enzyme inhibition, and antiproliferative effects were tested for biological activities. Chemical characterization was identified by GC-MS. Based on our findings, the Cymbopogon species may be utilized as sources of natural bioactive agents in food industries.Öğe Combinatorial peptide library screening for discovery of diverse alpha-glucosidase inhibitors using molecular dynamics simulations and binary QSAR models(TAYLOR & FRANCIS INC, 2019) Mollica, Adriano; Zengin, Gökhan; Durdağı, Serdar; Salmas, Ramin Ekhteiari; Macedonio, Giorgia; Stefanucci, Azzurra; Dimmito, Marilisa Pia; Novellino, EttoreHuman alpha-glucosidase is an enzyme involved in the catalytic cleavage of the glucoside bond and involved in numerous functionalities of the organism, as well as in the insurgence of diabetes mellitus 2 and obesity. Thus, developing chemicals that inhibit this enzyme is a promising approach for the treatment of several pathologies. Small peptides such as di- and tri-peptides may be in natural organism as well as in the GI tract in high concentration, coming from the digestive process of meat, wheat and milk proteins. In this work, we reported the first tentative hierarchical structure-based virtual screening of peptides for human alpha-glucosidase. The goal of this work is to discover novel and diverse lead compounds that my act as inhibitors of alpha-glucosidase such as small peptides by performing a computer aided virtual screening and to find novel scaffolds for further development. Thus, in order to select novel candidates with original structure we performed molecular dynamics (MD) simulations among the 12 top-ranked peptides taking as comparison the MD simulations performed on crystallographic inhibitor acarbose. The compounds with the lower RMSD variability during the MD, were reserved for in vitro biological assay. The selected 4 promising structures were prepared on solid phase peptide synthesis and used for the inhibitory assay, among them compound 2 showed good inhibitory activity, which validated our method as an original strategy to discover novel peptide inhibitors. Moreover, pharmacokinetic profile predictions of these 4 peptides were also carried out with binary QSAR models using MetaCore/MetaDrug applications.Öğe Discovery of kynurenines containing oligopeptides as potent opioid receptor agonists(MDPI AG, 2020) Szucs, Edina; Stefanucci, Azzurra; Dimmito, Marilisa Pia; Zádor, Ferenc; Pieretti, Stefano; Zengin, Gökhan; Vécsei, LászlóKynurenine (kyn) and kynurenic acid (kyna) are well-defined metabolites of tryptophan catabolism collectively known as “kynurenines”, which exert regulatory functions in host-microbiome signaling, immune cell response, and neuronal excitability. Kynurenine containing peptides endowed with opioid receptor activity have been isolated from natural organisms; thus, in this work, novel opioid peptide analogs incorporating L-kynurenine (L-kyn) and kynurenic acid (kyna) in place of native amino acids have been designed and synthesized with the aim to investigate the biological effect of these modifications. The kyna-containing peptide (KA1) binds selectively the ?-opioid receptor with a Ki = 1.08 ± 0.26 (selectivity ratio ?/?/? = 1:514:10000), while the L-kyn-containing peptide (K6) shows a mixed binding affinity for ?, ?, and ?-opioid receptors, with efficacy and potency (Emax = 209.7 + 3.4%; LogEC50 = ?5.984 + 0.054) higher than those of the reference compound DAMGO. This novel oligopeptide exhibits a strong antinociceptive effect after i.c.v. and s.c. administrations in in vivo tests, according to good stability in human plasma (t1/2 = 47 min). © 2020 by the authors. Licensee MDPI, Basel, Switzerland.Öğe Discovery of novel µ-opioid receptor inverse agonist from a combinatorial library of tetrapeptides through structure-based virtual screening(MDPI, 2019) Poli, Giulio; Dimmito, Marilisa Pia; Mollica, Adriano; Zengin, Gökhan; Benyhe, Sandor; Zador, Ferenc; Stefanucci, AzzurraMorphine, oxycodone, fentanyl, and other mu-opioid receptors (MOR) agonists have been used for decades in antinociceptive therapies. However, these drugs are associated with numerous side effects, such as euphoria, addiction, respiratory depression, and adverse gastrointestinal reactions, thus, circumventing these drawbacks is of extensive importance. With the aim of identifying novel peptide ligands endowed with MOR inhibitory activity, we developed a virtual screening protocol, including receptor-based pharmacophore screening, docking studies, and molecular dynamics simulations, which was used to filter an in-house built virtual library of tetrapeptide ligands. The three top-scored compounds were synthesized and subjected to biological evaluation, revealing the identity of a hit compound (peptide 1) endowed with appreciable MOR inverse agonist effect and selectivity over delta-opioid receptors. These results confirmed the reliability of our computational approach and provided a promising starting point for the development of new potent MOR modulators.Öğe Discovery of orexant and anorexant agents with indazole scaffold endowed with peripheral antiedema activity(MDPI, 2019) Dimmito, Marilisa P.; Stefanucci, Azzurra; Pieretti, Stefano; Minosi, Paola; Dvoracsko, Szabolcs; Tomboly, Csaba; Zengin, Gökhan; Mollica, AdrianoThe endocannabinoid system represents an integrated neuronal network involved in the control of several organisms' functions, such as feeding behavior. A series of hybrids of 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (mimonabant), a well-known inverse agonist of the type-1 cannabinoid receptor (CB1), once used as an antiobesity drug, and the N-(2S)-substitutes of 1-[(4-fluorophenyl)methyl]indazole-3-carboxamide with 1-amino-3-methyl-1-oxobutane (AB-Fubinaca), 1-amino-3,3-dimethyl-1-oxobutane (ADB-Fubinaca), and 3-methylbutanoate (AMB-Fubinaca), endowed with potent agonistic activity towards cannabinoid receptors CB1 and CB2 were in solution as C-terminal amides, acids, methyl esters and N-methyl amides. These compounds have been studied by binding assays to cannabinoid receptors and by functional receptor assays, using rat brain membranes in vitro. The most active among them as an agonist, (S)-1-(2,4-dichlorobenzyl)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-1H-indazole-3-carboxamide (LONI11), and an antagonist, (S)-2-(1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoic acid (LONI4), were tested in vivo in mic, to evaluate their ability to stimulate or suppress feeding behavior after intraperitoneal (i.p.) administration. For a LONI11 formalin test and a tail flick test after an administration by the subcutaneous (s.c.) and intracerebroventricular (i.c.v.) routes, respectively, were also carried out in vivo in mice to investigate the antinociceptive property at the central and peripheral levesl. We observed a significant orexant effect for LONI11 and an intense anorexant effect for (S)-methyl 2-(1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (LONI2) and LONI4. In zymosan-induced edema and hyperalgesia, LONI11 reduced the percent of paw volume increase and paw latency after s.c. administration, also suggesting a possible peripheral anti-inflammatory activity.Öğe Exogenous opioid peptides derived from food proteins and their possible uses as dietary supplements: A critical review(TAYLOR & FRANCIS INC, 2018) Stefanucci, Azzurra; Mollica, Adriano; Macedonio, Giorgia; Zengin, Gökhan; Ahmed, Abdelkareem A.; Novellino, EttoreEndogenous opioid peptides are neuro-hormones and neurotransmitters involved in several physiological actions such as stress reactions, nociception control, sedation, breathing tone, depression, hypotension, appetite, digestion, etc. It is now clear that hydrolysis by the digestion of certain food-proteins can lead to the production of bioactive peptides. Commonly diffused foods like milk, wheat, meat, and spinach may produce after enzymatic digestion a variable amount of opioid peptides. The aim of this review is to provide arising perspectives on opioid peptides, focusing on their production from milk, their potential benefits, drawbacks, and safety issues related to infants' feeding.Öğe Exploring the halophyte Cistanche phelypaea (L.) Cout as a source of health promoting products: In vitro antioxidant and enzyme inhibitory properties, metabolomic profile and computational studies(ELSEVIER, 2019) Trampetti, Francesca; Pereira, Catarina; Rodrigues, Maria Joao; Celaj, Odeta; D'Abrosca, Brigida; Zengin, Gökhan; Mollica, Adriano; Stefanucci, Azzurra; Custodio, LuisaIn this study, ethyl acetate, acetone, ethanol and water extracts from flowers, stems and roots of Cistanche phelypaea (L.) Cout were appraised for radical scavenging activity (RSA) towards 1,1-diphenyl-2-picrylhydrazyl,2,2-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) and superoxide free radicals, and for metal chelating activities on iron and copper ions. The water extracts had the highest antioxidant activity, especially those from roots and flowers, and were further appraised for in vitro inhibition of enzymes implicated on the onset of human ailments, namely acetyl- (AChE) and butyrylcholinesterase (BuChE) for Alzheimer's disease, alpha-glucosidase and alpha-amylase for diabetes, and tyrosinase for skin hyper-pigmentation disorders. The extracts had a higher activity towards BuChE, and the roots extract had the highest capacity to inhibit tyrosinase. Samples showed a low capacity to inhibit carbohydrate hydrolysing enzymes, except for the root extract with a good inhibition on glucosidase. Samples were then characterized by NMR (1D and 2D): the main metabolites identified in the flowers extract were iridoid glycosides, in particular gluroside and bartsioside. In stems, phenylehanoid glycosides (PhGs) and iri doids were detected, especially acteoside. In roots were detected essentially PhGs, mainly echinacoside and tubuloside A. Docking studies were performed on the identified compounds. A favorable binding energy of tubuloside A to tyrosinase was calculated, and indicated this compound as a possible competitive inhibitor of alpha-glucosidase and tyrosinase. Our results suggest that C. phelypeae is a promising source of biologically-active compounds with health promoting properties for pharmaceutical and biomedical applications. (C) 2018 Elsevier B.V. All rights reserved.Öğe In vitro and in silico Studies of Mangiferin from Aphloia theiformis on Key Enzymes Linked to Diabetes Type 2 and Associated Complications(BENTHAM SCIENCE PUBL LTD, 2017) Picot, Marie C. N.; Zengin, Gökhan; Mollica, Adriano; Stefanucci, Azzurra; Carradori, Simone; Mahomoodally, Mohamad F.Background: Mangiferin, was identified in the crude methanol extract, ethyl acetate, and n-butanol fractions of Aphloia theiformis (Vahl.) Benn. Objective: This study aimed to analyze the plausible binding modes of mangiferin to key enzymes linked to diabetes type 2 (DT2), obesity, hypertension, Alzheimer's disease, and urolithiasis using molecular docking. Method: Crystallographic structures of alpha-amylase, alpha-glucosidase, glycogen phosphorylase (GP), pancreatic lipase, cholesterol esterase (CEase), angiotensin-I-converting enzyme (ACE), acetyl cholinesterase (AChE), and urease available on the Protein Databank database were docked to mangiferin using Gold 6.0 software. Results: We showed that mangiferin bound to all enzymes by pi-pi and hydrogen bonds mostly. Mangiferin was docked to both allosteric and orthosteric sites of a-glucosidase by pi-pi interactions. However, several hydrogen bonds were observed at the orthosteric position, suggesting a preference for this site. The docking of mangiferin on AChE with the catalytic pocket occupied by paraoxon could be attributed to pi-pi stacking involving amino acid residues, Trp341 and Trp124. Conclusion: This study provided an insight of the molecular interaction of mangiferin with the studied enzymes and can be considered as a valuable tool for designing new drugs for better management of these diseases.Öğe Metabolomics profiling, bio-pharmaceutical properties of Hypericum lanuginosum extracts by in vitro and in silico approaches(ELSEVIER SCIENCE BV, 2019) Mahomoodally, Mohamad Fawzi; Zengin, Gökhan; Zheleva-Dimitrova, Dimitrina; Mollica, Adriano; Stefanucci, Azzurra; Sinan, Kouadio Ibrahime; Aumeeruddy, Muhammad ZakariyyahHypericum species are important as a source of natural-bioactive compounds in the Turkish folk medicine. Among them, Hypericum lanuginosum has not been explored so far for its biological properties. The current study aimed to determine the antioxidant activity, enzyme inhibitory potential, and phenolic content (spectrophotometric and liquid chromatography/high resolution mass spectrometry (LC-HRMS) analysis) of different solvent extracts (ethyl acetate, methanol, and aqueous) of H. lanuginosum aerial parts. Twenty one phenolic compounds including phenolic acids, acylquinic acids, flavonoids and bioflavonoids were identified by LC-HRMS profiles. Quinic acid was the dominant compound in all H. lanuginosum extracts. The highest total phenolic (168.56 mg gallic acid equivalent (GAE)) and flavonoid (53.22 mg rutin equivalent (RE)) contents were observed in the aqueous extract. Also, the aqueous extract was the best antioxidant, showing the highest 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) scavenging, ferric reducing antioxidant power (FRAP), cupric reducing antioxidant capacity (CUPRAC), and activity in the phosphomolybdenum assay. The methanol extract exhibited the strongest metal chelating and inhibitory effect on alpha-amylase and tyrosinase. In contrast, the most efficient inhibitor of cholinesterases and alpha-glucosidase was the ethyl acetate extract. Docking showed that the selected compounds are all possible inhibitor candidates of tyrosinase. To conclude, each solvent extract of H. lanuginosum varied in its chemical and biological profile but overall, possess a good source of many natural agents which can be used to manage ailments inked with oxidative stress.Öğe Multi-targeted potential of Pittosporum senacia Putt.: HPLC-ESI-MSn analysis, in silico docking, DNA protection, antimicrobial, enzyme inhibition, anticancer and apoptotic activity(ELSEVIER SCI LTD, 2019) Mahomoodally, Mohamad Fawzi; Picot-Allain, Carene; Hosenally, M.; Uğurlu, Aslı; Mollica, Adriano; Stefanucci, Azzurra; Llorent-Martinez, E. J.; Baloğlu, Mehmet Cengiz; Zengin, GökhanPittosporum senacia (PS) Putt. (Pittosporaceae), indigenous to the Mascarene Islands, is a common ingredient in traditional medicines. However, there is currently a dearth of studies to validate some of these traditional claims. Given the broad traditional uses of PS against several diseases, we aimed to provide a comprehensive insight into the biological and chemical profile of P. senacia. The antioxidant, enzyme inhibitory activity, anticancer, and phytochemical composition of the methanolic extract of P. senacia leaf extracts were studied. The possible interaction and binding mode of the most abundant phytochemicals were studied via in silico docking experiments on tyrosinase and alpha-glucosidase. The mechanism behind the cytotoxic property of P. senacia extract for MDA-MB-231 was also examined using different methods including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability test checking apoptosis-associated genes, and wound healing assays. Twenty-six compounds were identified, of which caffeoylquinic acid derivatives, ferulic acid derivative, cinnamoylquinic acid derivative and two other polyphenols (oleuropeine and isoramnetin glucoside) being abundant, have been tested using in silico studies, against alpha-glucosidase and tyrosinase. The extract (IC50 = 118.8 mu g/ml) exhibited time and dose dependent anti-proliferative effect on human breast cancer cell line, MDA-MB-231. According to the expression profile of apoptosis inhibitors and apoptosis promoters genes, expression of Bar and Bak genes were significantly increased compared to Bcl-2 and Birc5 genes. Based on wound healing analysis, cell migration was inhibited after the application of the plant extract. The present findings suggested that PS might be a good candidate as sources of bioactive compounds for designing functional applications.Öğe Multifunctional approaches to provide potential pharmacophores for the pharmacy shelf: Heracleum sphondylium L. subsp. ternatum (Velen.) Brummitt(ELSEVIER SCI LTD, 2019) Uysal, Ahmet; Özer, Ömer Yılmaz; Zengin, Gökhan; Stefanucci, Azzurra; Mollica, Adriano; Picot-Allain, Carene Marie Nancy; Mahomoodally, Mohamad FawziHeracleum sphondylium L. subsp. ternatum (Velen.) Brummitt. commonly known as "hogweed" is traditionally used to manage several human ailments. This investigation assessed, for the first time, the enzyme inhibitory properties, antioxidant activity, phytochemical profile, antimutagenic, and antimicrobial potential of the ethyl acetate, methanol, and water extracts of H. sphondylium. We also established the possible interactions of identified phenolic compounds with cholinesterases, amylase, glucosidase, and tyrosinase using in silico docking studies. Chlorogenic acid was found in high amounts in the methanol extract of H. sphondyliurn. The methanol extract was an effective inhibitor of acetylcholinesterase (1.70 mg galantamine equivalent (GALAE)/g extract) while the ethyl acetate extract showed pronounced inhibitory action against butyrylcholinesterase (1.77 mg GALAE/g extract). The extracts exhibited low inhibition against amylase (0.12-0.84 mmol acarbose equivalent (ACAE)/g extract) and a more pronounced inhibition against glucosidase (2.29-3.65 mmol ACAE/g extract). In silico results showed that rutin and quercetin (-70.4 and -72.2 Kcal/mol, for rutin and quercetin respectively) docked to the enzymatic cavity of acetylcholinesterase but these phenolic compounds showed less affinity with butyrylcholinesterase (-15.0 and -5.2 Kcal/mol, for rutin and quercetin respectively). The extracts did not induce any mutations on the bacterial strains, while they have excellent antimutagenic capacity against well-known mutagens (inhibition values 98%, 97% and 96%). The methanol extract (0.78 mg/ml) showed moderate antifungal activity while the ethyl acetate extract (0.78-3.12 mg/ml) showed weak to moderate antimicrobial activity. This study provides valuable baseline data which might serve for the development of future pharmacophores for the management of human ailments.Öğe Nutraceutical potential of Corylus avellana daily supplements for obesity and related dysmetabolism(ELSEVIER SCIENCE BV, 2018) Mollica, Adriano; Zengin, Gökhan; Stefanucci, Azzurra; Ferrante, Claudio; Menghini, Luigi; Orlando, Giustino; Brunetti, LuigiIn this study, the nutraceutical potential of two hazelnut varieties (Turkey and Italy) were examined by studying several aspects including the phytochemical properties, antioxidant potential, cell viability and ex vivo neuroprotective potential. Results showed that the Turkish hazelnut had the higher concentration of phenolic acids, flavonoids, higher antioxidant capacity and enzyme inhibition properties and lower saturated fatty acid concentration than the Italian sample. The in vivo studies showed that compared to the Italian hazelnuts, the addition of Turkish hazelnuts to high fat diet was associated with a more significant decrease in body weight, food consumption, atherogenic index, lipid peroxidation levels and biochemical/morphological markers of liver injury. Also, from our results, the two hazelnut varieties were protective against beta-amyloid-induced neurochemical changes and high-fat diet induced alteration of metabolic indices.Öğe Scrophularia Lucida L. As A Valuable Source Of Bioactive Compounds For Pharmaceutical Applications: In Vitro Antioxidant, Anti-İnflammatory, Enzyme İnhibitory Properties, İn Silico Studies, And HPLC Profiles(ELSEVIER SCIENCE BV, 2019) Zengin, Gökhan; Stefanucci, Azzurra; Rodrigues, Maria Joao; Mollica, Adriano; Custodio, Luisa; Aumeeruddy, Muhammad Zakariyyah; Mahomoodally, Mohamad FawziThe genus Scrophularia has received much interest with regards to its traditional uses against eczema, psoriasis, and mastitis. Yet, the medicinal properties of some species still need to be scientifically validated. The present study was designed to investigate into the biological properties of various solvent extracts (ethyl acetate, methanol, and aqueous) of the roots and aerial parts of Scrophularia lucida based on its antioxidant, anti-inflammatory, and enzyme inhibitory activities together with phytochemical screening. Our results revealed that the solvent extracts differed in their biological effectiveness. The root ethyl acetate extract showed the highest ABTS scavenging, FRAP, CUPRAC, and inhibitory activity against AChE and alpha-glucosidase. The ethyl acetate extract of the aerial parts displayed the highest BChE and alpha-amylase inhibition and antioxidant effect in the phosphomolybdenum assay, while the methanol extracts of both parts were the most effective DPPH center dot scavengers and tyrosinase inhibitors. The methanol extracts of the root and aerial parts also inhibited NO production in lipopolysaccharide (LPS)-stimulated murine leukemic monocyte-macrophage cell (4.99% and 10.77%, respectively), at 31.25 mu g/mL concentration. The highest TPC (34.98 mg GAE/g extract) and TFC (48.33 mg RE/g extract) were observed in the ethyl acetate extract of the root and aerial parts, respectively. The most abundant compounds in the root ethyl acetate extract were luteolin (852 mu g/g extract), rosmarinic acid (522 mu g/g extract), and hesperidin (394 mu g/g extract) while kaempferol was most abundant in the ethyl acetate extract of the aerial parts (628 mu g/g extract). In silico experiments were conducted on tyrosinase and the higher docking values were observed for rosmarinic acid and hesperidin. The present findings provide base line information which tend to support the potential use of S. lucida in the management of several chronic diseases, including Alzheimer's disease and diabetes mellitus. (C) 2018 Elsevier B.V. All rights reserved.
