Gastritis is an inflammatory-based disease, involving millions of people in the world. Helicobacter pylori (H. pylori) is the main cause of inflammation at the gastric level, inducing the expression and release of different pro-inflammatory cytokines (ex. IL-8 and IL-6) by gastric epithelial cells. The presence of H. pylori results also in reactive oxygen species (ROS) production by the gastric mucosa; gastric epithelial cells contribute to the production of ROS, thus exacerbating oxidative stress in this district. Strawberry is one of the most commonly consumed fruits in the world and it is an important source of sugars, vitamins, fibers, micronutrients and polyphenols, including anthocyanosides (i.e. pelargonidin and cyanidin glycosides) and tannins. Condensed (procyanidins) and hydrolysable tannins (especially ellagitannins, such as agrimoniin) are among the most abundant polyphenols. Although tannins are important components of strawberries, until now the activity of these strawberry compounds, on gastric inflammation, is unknown. In the present study, the chemical profile and the biological properties of tannin-enriched extracts from strawberries were analyzed in cell models of gastric inflammation, considering also the chemical and biological features of strawberry tannins after in vitro simulated gastric digestion. The anti-inflammatory activities of pure strawberry tannins were assayed to get mechanistic insights. Tannin-enriched extracts from strawberries inhibit IL-8 secretion in TNFα-treated human tumour gastric epithelial cells (AGS) by dampening the NF-κB signaling. In vitro simulated gastric digestion slightly affects the chemical composition and the biological properties of strawberry tannins. By using pure compounds, I found that casuarictin may act as a pure NF-B inhibitor while agrimoniin inhibits IL-8 secretion also acting on other biological targets; in our system procyanidin B1 prevents the TNFα-induced effects without interfering with the NF-κB pathway. The effects of strawberry tannins are maintained in normal gastric epithelial cells (GES-1) showing an inhibitory effect on NF-κB activity and the expression and release of some pro-inflammatory mediators (like IL-8, IL-6 and MMP-9). Comparing the IC50s between AGS and GES-1 cells, the activity of strawberry tannins appear slightly higher in AGS cells than in GES-1 cells. Compounds from strawberry are able to counteract H. pylori-induced IL-8 release in both GES-1 and AGS cells, although the effect appears at higher concentrations than in TNFα-treated cells. Concentrations showing efficacy are easily reachable in vivo after with a moderate consumption of the fruit. Agrimoniin and casuarictin are able to exert an antioxidant activity in a cell-free system and to suppress basal Nrf2 activation. Taken together these results suggest that strawberry tannins, even after in vitro simulated gastric digestion, exert anti-inflammatory activities at nutritionally relevant concentrations.

STRAWBERRY (FRAGARIA X ANANASSA DUCH.) TANNINS AS INGREDIENTS OF NUTRACEUTICALS WITH POTENTIAL ANTI-GASTRITIS PROPERTIES / M. Fumagalli ; TUTOR: M. DELL'AGLI ; COORDINATORE: A.L. CATAPANO. - : . DIPARTIMENTO DI SCIENZE FARMACOLOGICHE E BIOMOLECOLARI, 2018 Dec 17. ((31. ciclo, Anno Accademico 2018. [10.13130/fumagalli-marco_phd2018-12-17].

STRAWBERRY (FRAGARIA X ANANASSA DUCH.) TANNINS AS INGREDIENTS OF NUTRACEUTICALS WITH POTENTIAL ANTI-GASTRITIS PROPERTIES

FUMAGALLI, MARCO
2018-12-17

Abstract

Gastritis is an inflammatory-based disease, involving millions of people in the world. Helicobacter pylori (H. pylori) is the main cause of inflammation at the gastric level, inducing the expression and release of different pro-inflammatory cytokines (ex. IL-8 and IL-6) by gastric epithelial cells. The presence of H. pylori results also in reactive oxygen species (ROS) production by the gastric mucosa; gastric epithelial cells contribute to the production of ROS, thus exacerbating oxidative stress in this district. Strawberry is one of the most commonly consumed fruits in the world and it is an important source of sugars, vitamins, fibers, micronutrients and polyphenols, including anthocyanosides (i.e. pelargonidin and cyanidin glycosides) and tannins. Condensed (procyanidins) and hydrolysable tannins (especially ellagitannins, such as agrimoniin) are among the most abundant polyphenols. Although tannins are important components of strawberries, until now the activity of these strawberry compounds, on gastric inflammation, is unknown. In the present study, the chemical profile and the biological properties of tannin-enriched extracts from strawberries were analyzed in cell models of gastric inflammation, considering also the chemical and biological features of strawberry tannins after in vitro simulated gastric digestion. The anti-inflammatory activities of pure strawberry tannins were assayed to get mechanistic insights. Tannin-enriched extracts from strawberries inhibit IL-8 secretion in TNFα-treated human tumour gastric epithelial cells (AGS) by dampening the NF-κB signaling. In vitro simulated gastric digestion slightly affects the chemical composition and the biological properties of strawberry tannins. By using pure compounds, I found that casuarictin may act as a pure NF-B inhibitor while agrimoniin inhibits IL-8 secretion also acting on other biological targets; in our system procyanidin B1 prevents the TNFα-induced effects without interfering with the NF-κB pathway. The effects of strawberry tannins are maintained in normal gastric epithelial cells (GES-1) showing an inhibitory effect on NF-κB activity and the expression and release of some pro-inflammatory mediators (like IL-8, IL-6 and MMP-9). Comparing the IC50s between AGS and GES-1 cells, the activity of strawberry tannins appear slightly higher in AGS cells than in GES-1 cells. Compounds from strawberry are able to counteract H. pylori-induced IL-8 release in both GES-1 and AGS cells, although the effect appears at higher concentrations than in TNFα-treated cells. Concentrations showing efficacy are easily reachable in vivo after with a moderate consumption of the fruit. Agrimoniin and casuarictin are able to exert an antioxidant activity in a cell-free system and to suppress basal Nrf2 activation. Taken together these results suggest that strawberry tannins, even after in vitro simulated gastric digestion, exert anti-inflammatory activities at nutritionally relevant concentrations.
DELL'AGLI, MARIO
CATAPANO, ALBERICO LUIGI
Gastric inflammation; tannins; strawberry; Helicobacter pylori
Settore BIO/14 - Farmacologia
STRAWBERRY (FRAGARIA X ANANASSA DUCH.) TANNINS AS INGREDIENTS OF NUTRACEUTICALS WITH POTENTIAL ANTI-GASTRITIS PROPERTIES / M. Fumagalli ; TUTOR: M. DELL'AGLI ; COORDINATORE: A.L. CATAPANO. - : . DIPARTIMENTO DI SCIENZE FARMACOLOGICHE E BIOMOLECOLARI, 2018 Dec 17. ((31. ciclo, Anno Accademico 2018. [10.13130/fumagalli-marco_phd2018-12-17].
Doctoral Thesis
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/606032
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