Inflammatory bowel diseases (IBD) are a group of disorders involving the colon and small intestine and are characterized by a persistent immune-mediated inflammatory state that leads to alteration of the gastrointestinal tract. Currently, the main drugs used for the treatment of IBD are not free of side effects and often do not lead to therapeutic success. Therefore, the discovery of new substances of plant origin, capable of preventing or reducing intestinal inflammation could represent a valid alternative to conventional therapies. Cynara cardunculus L. is an herbaceous plant abundantly used as food or as drug in traditional medicine, and its leaves contain numerous polyphenols which have antioxidant and anti-inflammatory activities. Since the leaves represent a food waste material but are a source of bioactive compounds, they could be used to obtain extracts rich in polyphenols. Therefore, the objective of this work was to determine the intracellular mechanisms involved in the protective effects of a standardized extract obtained from the leaves of Cynara cardunculus L. (CCLE), rich in chlorogenic acid and luteolin derivates, against TNF-α-induced intestinal epithelial inflammation by using an in vitro intestinal epithelial system consisting of filter grown Caco-2 monolayers. CCLE demonstrated the ability to suppress NF-κB inflammatory pathway activation induced by TNF-α in addition to IL-8 and COX-2 overexpression. Furthermore, CCLE restored the intracellular redox state altered by TNF-α by increasing the values of TAA and GSH, important markers of the intracellular redox state, both in cells exposed and not to TNF-α. Finally, it has been shown that the beneficial effects of CCLE against intestinal inflammation induced by TNF-α are due to the ability of this extract to stimulate an adaptive cellular response by activating the Nrf2 pathway. In conclusion, our data evidenced that the protective effects of CCLE, rich in polyphenols, are due to its ability to modulate the cellular signaling pathways involved in redox state and inflammation. Indeed, CCLE suppresses NF-κB and activates Nrf2 pathways. Finally, this study demonstrates the possibility of using Cynara cardunculus L. leaves, considered waste products, to obtain extracts rich in polyphenols potentially useful for the prevention and treatment of intestinal inflammatory disorders.

In vitro beneficial effects of a standardized extract from Cynara cardunculus L. leaves against intestinal inflammation induced by TNF-α in Caco-2 cells.

Claudia Muscara';Maria Sofia Molonia;Giovanni Toscano;Francesco Cimino;Antonina Saija;Antonio Speciale
2022-01-01

Abstract

Inflammatory bowel diseases (IBD) are a group of disorders involving the colon and small intestine and are characterized by a persistent immune-mediated inflammatory state that leads to alteration of the gastrointestinal tract. Currently, the main drugs used for the treatment of IBD are not free of side effects and often do not lead to therapeutic success. Therefore, the discovery of new substances of plant origin, capable of preventing or reducing intestinal inflammation could represent a valid alternative to conventional therapies. Cynara cardunculus L. is an herbaceous plant abundantly used as food or as drug in traditional medicine, and its leaves contain numerous polyphenols which have antioxidant and anti-inflammatory activities. Since the leaves represent a food waste material but are a source of bioactive compounds, they could be used to obtain extracts rich in polyphenols. Therefore, the objective of this work was to determine the intracellular mechanisms involved in the protective effects of a standardized extract obtained from the leaves of Cynara cardunculus L. (CCLE), rich in chlorogenic acid and luteolin derivates, against TNF-α-induced intestinal epithelial inflammation by using an in vitro intestinal epithelial system consisting of filter grown Caco-2 monolayers. CCLE demonstrated the ability to suppress NF-κB inflammatory pathway activation induced by TNF-α in addition to IL-8 and COX-2 overexpression. Furthermore, CCLE restored the intracellular redox state altered by TNF-α by increasing the values of TAA and GSH, important markers of the intracellular redox state, both in cells exposed and not to TNF-α. Finally, it has been shown that the beneficial effects of CCLE against intestinal inflammation induced by TNF-α are due to the ability of this extract to stimulate an adaptive cellular response by activating the Nrf2 pathway. In conclusion, our data evidenced that the protective effects of CCLE, rich in polyphenols, are due to its ability to modulate the cellular signaling pathways involved in redox state and inflammation. Indeed, CCLE suppresses NF-κB and activates Nrf2 pathways. Finally, this study demonstrates the possibility of using Cynara cardunculus L. leaves, considered waste products, to obtain extracts rich in polyphenols potentially useful for the prevention and treatment of intestinal inflammatory disorders.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3229579
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