Schisano, Connie (2020) Research and development of nutraceuticals useful for metabolic syndrome and inflammatory diseases. [Tesi di dottorato]


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Item Type: Tesi di dottorato
Lingua: English
Title: Research and development of nutraceuticals useful for metabolic syndrome and inflammatory diseases.
Date: 12 March 2020
Number of Pages: 140
Institution: Università degli Studi di Napoli Federico II
Department: Farmacia
Dottorato: Scienza del farmaco
Ciclo di dottorato: 32
Coordinatore del Corso di dottorato:
D'Auria, Maria
Tenore, Gian CarloUNSPECIFIED
Date: 12 March 2020
Number of Pages: 140
Uncontrolled Keywords: nutraceuticals; metabolic syndrome; chia seeds; peptides; abscisic acid
Settori scientifico-disciplinari del MIUR: Area 03 - Scienze chimiche > CHIM/10 - Chimica degli alimenti
Date Deposited: 19 Mar 2020 11:30
Last Modified: 08 Nov 2021 13:39


Metabolic syndrome (MetS) represents a cluster of metabolic abnormalities that include hypertension, central obesity, insulin resistance, and atherogenic dyslipidaemia, and is strongly associated with an increased risk for developing diabetes and atherosclerotic and nonatherosclerotic cardiovascular disease (CVD). The pathogenesis of MetS involves both genetic and acquired factors that contribute to the final pathway of inflammation that leads to CVD. MetS has gained significant importance recently due to the exponential increase in obesity worldwide. Early diagnosis is important in order to employ lifestyle and risk factor modification, and the research of novel natural remedies for prevention and treatment of MetS is the basis of reduction of standard therapy side effects. In the present thesis, I focused the attention on omega-3 and omega-6 fatty acids, milk-derived peptides and abscisic acid, three compounds potentially involved in the regulation of plasma triglycerides, intestinal permeability and glycaemia. Three nutraceutical sources have been considered, Salvia hispanica L., Buffalo Mozzarella cheese and peschiole, as a novel complementary and/or alternative safe remedy with clinical relevance in the MetS prevention. The first aim was to test a chia seed-based nutraceutical formulation (CSN) for its potential effects on plasma triglyceride levels of healthy subjects with moderate dyslipidaemia. A cohort of 52 individuals were administered daily, for 8 weeks, with four gastro-resistant capsules of CSN, each one containing 500 mg of cryo-micronized chia seeds and 15 mg of vitamin E, according to a single centre, randomised, placebo controlled, 16 weeks trial. Data showed the following mean lipid changes: triglycerides, −27.5% (P = .0095); total cholesterol, −8.0% (P = .0019); High Density Lipoprotein cholesterol, +5.7% (P = .0042); Low Density Lipoprotein cholesterol, −10.2% (P = .0021). Secondly, the bioactive properties of milk and milk-products are largely attributed to the peptides released during gastrointestinal digestion. Nevertheless, no similar studies on “Mozzarella di Bufala Campana DOP” (MBC), the European name given to a unique protected origin designation buffalo milk product, are available so far. A novel antioxidant peptide (MBCP) after MBC gastrointestinal digestion was identified and its in vitro intestinal protection, bioavailability, and anti-haemolytic capacity were assayed. A 0.2 mg/ml MBCP incubation dose made H2O2-stressed CaCo2 cell line proliferation increase by about 100%. Less than 10% hydrolysis in the apical solution and about 10% concentration in the basolateral solution indicated for MBCP good stability and bioavailability, respectively. A 0.2 mg/ml MBCP incubation dose reduced H2O2-induced human erythrocyte haemolysis by 91.25%. The next step was to evaluate the therapeutic potential of MBCP in inflammatory bowel disease (IBD). I studied the effect of MBCP on (i) inflamed human intestinal Caco2 cells, (ii) dinitrobenzene sulfonic acid (DNBS) mice model of colitis and (iii) the administration in a clinical trial of a nutraceutical formulation corresponding quali-quantitative to MBCP composition. I have shown that MBCP, at non-cytotoxic concentrations, both in vitro and in vivo induced the adherens epithelial junctions organization, modulated the nuclear factor (NF)-κB pathway and reduced the intestinal permeability. Furthermore, the clinical trial showed, after 8 weeks of treatment, a reduction of lactulose/mannitol ratio, an index on intestinal permeability, of -75.2% (P < .01). The results obtained underline that MBCP possesses anti-inflammatory effects both in vitro and in vivo, and it is confirmed by a randomised, placebo controlled, study. Lastly, I tested the effect of a peschiole-based novel nutraceutical formulation, rich in abscisic acid, on the metabolic parameters that are dysregulated in prediabetes and MetS. A cohort of 20 patients were administered daily, for 12 weeks, with two sachets for meal (breakfast, lunch, and dinner) corresponding to 30 μg abscisic acid. Data showed the following metabolic parameters mean: glycaemia, -26,85% *; insulin, -33,63% *; HOMA-IR, -58,89% *; glycated haemoglobin (HbA1c), -20,18% * (*P < .01). Thus, CSN showed a clinical relevance in the primary cardiovascular disease prevention, MBCP helps to restore the intestinal epithelium integrity damaged by inflammation, and peschiole-based novel nutraceutical formulation may control plasma glycaemia, collaborating in the development of nutraceuticals useful for the treatment and prevention of MetS.


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