D'Urso, Emanuela (2017) Nutraceutical potential of vegetal food products typical of Campania region: Mela Annurca Campana IGP. [Tesi di dottorato]

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The nutraceutical potential of a specific apple cultivar, “Annurca”, was evaluated by both in vitro and in vivo studies. Particularly, the effects of Annurca polyphenolic extract on lipid uptake and metabolism were evaluated and compared with those obtained from polyphenolic extracts coming from other conventional cultivars. In vitro experiments performed on HepG2 (human hepatocellular liver carcinoma) cells indicated Annurca flesh polyphenolic extract as the most active in reducing cholesterol and triglyceride uptake (about, 15 and 20 times than control cells, respectively), in inhibiting lipase activity (-55% than control cells), in enhancing low-density lipoprotein (LDL) receptor binding activity (+46% than control cells), in increasing Apolipoprotein A1 (ApoA1) cell expression (+71.4% above control levels) and in protecting from oxidative stress (cell proliferation: +47.5%; cell radical levels: -33.3% than control cells). All the amazing in vitro properties of Annurca flesh polyphenolic extract were attributed to its high content in procyanidins, and good linear correlations between procyanidin content and cellular effects were registered. In vitro experiments of gastrointestinal digestion showed a good bioaccessibility of apple procyanidins during the three digestive steps. After salivary digestion, their bioaccessibility was 35% of undigested samples, suggesting a potential good absorption through the oral mucosa, and it increased during gastric (+5.1% compared to salivary digestion) and intestinal (+16% in respect to gastric digestion) phases. However, their bioavailability was very low (6.7% of their native pattern and 12.0% of the intestinal digestion), suggesting they would act mainly in the gut. The small portion absorbed was strongly bound to plasma proteins (93.4%), especially to high-density lipoproteins (HDLs, 58.7%), suggesting a role in cholesterol metabolism. The results of the first clinical trial showed that Annurca apple was the most effective, since it decreased total cholesterol (TC, -8.4%) and low-density lipoprotein cholesterol (LDL-C, -14.5%) levels, and raised high-density lipoprotein cholesterol levels (HDL-C, +14.0%). The results of the second clinical trial showed that the treatment with AppleMetS™ (AMS) resulted in a significant decrease in plasma LDL-C levels (-37.5%), an effect comparable to that obtained after treatment with 40 mg of simvastatin or 10 mg of atorvastatin. Moreover, it increased HDL-C levels of about 49.2%, an effect never observed in any pharmaceutical or nutraceutical substance. These amazing results suggested that Annurca polyphenols represent an important tool for the treatment of mild hypercholesterolemia, especially in elderly people with higher values of baseline total cholesterol.

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