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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 An assessment of the nutraceutical potential of Juglans regia L.leaf powder in diabetic rats(PERGAMON-ELSEVIER SCIENCE LTD, 2017) Mollica, Adriano; Zengin, Gökhan; Locatelli, Marcello; Stefariucci, Azzurra; Macedonio, Giorgia; Bellagamba, Giuseppe; Onaolapo, OlakunleIn this study, we evaluated the nutraceutical potential of juglans regia L (a dietary supplement and food additive) by evaluating the in-vitro anti-diabetic potential and by assessing the in-vivo anti hyperglycaemic, anti-hyperlipidaemic, and organ-protective effects of freshly-dried and powdered leaves of J. regia L in diabetic rats. In the in-vivo experiments, dry powder of J. regia L leaf (25, 50 and 100 mg/kg) was administered orally, twice daily (9.00 a.m. and 5 p.m.) to streptozocin-induced diabetic rats over a period of 28 days, during which body weight and blood glucose were monitored weekly. At the end of the experimental period, animals were sacrificed, blood was taken for assessment of lipid profile, antioxidant activity and liver/kidney biochemistry; while samples of the pancreas, liver and kidneys were fixed, processed, sectioned, and stained for general histology. Phytochemical evaluations of three extracts were carried out using HPLC-PDA validated procedures, while enzyme-inhibitory potentials were tested against alpha-amylase and alpha-glucosidase. In-vivo assays showed that twice-daily administration of J. regia L leaf resulted in weight gain, glycaemic control, reversal of dyslipidaemia and biochemical evidences of liver/kidney injury, and protection against pancreas, liver and kidney tissue injury. (C) 2017 Elsevier Ltd. All rights reserved.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 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 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 Microwave-assisted extraction, HPLC analysis, and inhibitory effects on carbonic anhydrase I, II, VA, and VII isoforms of 14 blueberry Italian cultivars(TAYLOR & FRANCIS LTD, 2016) Mollica, Adriano; Locatelli, Marcello; Macedonio, Giorgia; Carradori, Simone; Sobolev, Anatoly P.; De Salvador, Roberto F.; Monti, Simona M.The multi-component fingerprint and the biological evaluation of plant-derived material are indispensable for the pharmaceutical field, in food quality control procedures, and in all plant based products. We investigated the quantitative content of biologically active compounds (anthocyanins and chlorogenic acid) of microwave-assisted blueberry extracts from 14 different Italian cultivars, using validated high-performance liquid chromatography-photodiode array detector (HPLC-PDA) method and routinely instrument configuration. The carbonic anhydrase (CA, EC 4.2.1.1) inhibition profiles against several pharmacologically relevant CA isoforms of blueberry extracts and some bioactive compounds were also investigated. The various cultivars showed a highly variable content in anthocyanins and chlorogenic acid, and their CA inhibitory effects were also highly variable. Overall these data prove that antioxidant natural products found in blueberries may be useful for designing pharmacological agents in which various CAs are involved, e.g., antiobesity, antitumor, or anticonvulsants agents.