Novel colon‐available triterpenoids identified in raspberry fruits exhibit antigenotoxic activities in vitro

Abstract

Abbreviations: CDDO = 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid; FAV = fruit and vegetables; GI = gastrointestinal; TRF = triterpenoid-rich fraction;Key words: Raspberries, metabolic profiling, triterpenoids, colon cancer, ileal fluid ABSTRACT Scope: Ileostomy studies provide a unique insight into digestion of food, allowing identification of physiologically relevant dietary phytochemicals and their metabolites important to gut health. We previously reported the consistent increase of components in ileal fluids of ileostomates after consumption of raspberries with use of non-targeted LC-MS n techniques and data deconvolution software highlighting two major unknown components (m/z 355 and 679). Methods and results:In-depth LC-MS n analyses suggested that the ileal m/z 355 components were p-coumaroyl glucarates. These compounds have not been identified previously and were confirmed in raspberry extracts after partial purification. The major ileal component with m/z 679 was a glycoside with an aglycone of m/z 517 and was present as two peaks in extracts of whole puree, unseeded puree and isolated seeds. These components were purified using Sephadex LH20 and C18 SPE units and identified as major, novel raspberry triterpenoid glycosides. This triterpenoid-enriched fraction (100 nM)protected against H 2 O 2 -induced DNA damage in both colon cancer and normal cell lines and altered expression of cytoprotective genes. Conclusion:The presence of these novel raspberry triterpenoid components in ileal fluids indicates that they would be colon-available in vivo, so confirmation of their anti-cancer bioactivities is of key physiological relevance.www.mnf-journal.comThis article is protected by copyright. All rights reserved.Two major unknown components present in ileal fluids after intake of raspberries were identified as triterpenoid glycosides and p-coumaroyl glucarates using LC-MS n analysis. The triterpenoids were purified from raspberries and were shown to have genoprotective effects at sub-micromolar levels against H 2 O 2 -induced damage in colon cell lines. Therefore these novel triterpenoids combine established colonic bioavailability with potential bioactivity at physiological doses. INTRODUCTIONThere is great interest in the possibility that non-nutritive components could directly contribute to the health benefits attributable to a diet rich in fruit and vegetables (FAV) [1][2][3].One set of phytochemicals of specific interest are the (poly)phenols as are found in high concentrations in certain beverages and FAV, such as berries, and have been attributed a range of important bioactivities [4][5][6][7][8][9]. However, an important issue with ascribing any potential health benefit is the long held view that the bioavailability of many (poly)phenol classes is low. For example, urinary recoveries of anthocyanins, which reflect passage through the circulatory system, are typically <<1% of intake [10], although recent studies with Although previous targeted liquid chromatography mass spectrometry (LC-MS n ) analyses[...

Effect of simulated gastrointestinal digestion and fermentation on polyphenolic content and bioactivity of brown seaweed phlorotannin‐rich extracts

“…In addition, after CF all extracts showed a further reduction of TP and antioxidant capacity, thus they were able to significantly reduce H 2 O 2 -induced DNA damage, indicating how the potential beneficial effects of the extracts are not linked to their in vitro antioxidant potential. Our results are consistent with observations of (poly)phenolic compounds from other terrestrial dietary sources [53][54][55][56]. Our results also highlight the strong impact of GID and CF on the ability of the extracts to induce cell growth inhibition on HT-29 cells.…”

Bioprospection of Natural Sources of Polyphenols with Therapeutic Potential for Redox-Related Diseases

“…The potential of berry extracts to modulate cancer disease progression have been shown both via in vitro and in vitro models and anthocyanins have been found to be major contributors towards inhibiting cell proliferation and inducing apoptosis [ 55 ]. Dietary triterpenoids, which are often found in Rubus species, are able to survive in vivo digestion [ 56 ] and have shown promising results in pre-clinical trials in colorectal cancer models [ 57 ]. Interestingly, (−)-epicatechin has been found to provide synergistic effects in modulating growth and apoptosis in human cancerous cell cultures when combined with other phytochemicals such as curcumin [ 58 ] and EGCG [ 59 ], whereas epidemiological evidence found association between dietary intake of catechin-derived compounds and reduced colorectal cancer incidence [ 60 , 61 ].…”

Lupeol inhibits growth and migration in two human colorectal cancer cell lines by suppression of Wnt&ndash;&beta;-catenin pathway

“…Epidemiological evidence has shown an association between triterpenoid-enriched plant intake and decreased risk of developing CRC. 13 Likewise, considerable evidence has shown that triterpenoids, such as lupeol, show an antitumor effect in certain cell lines. 14 , 15 DNA damage is identified as a premise of cancer development, and lupeol has the potentiality to inhibit chemically induced DNA damage, both in vitro and in vivo.…”