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    • Since the beginning of s more than

    2023-12-29

    Since the beginning of 1990s, more than 17,000 papers about physiological relevance of antioxidants have been published according to data from web of science. Based on the available literature, it seems that assessing the antioxidant potential of food by means of in vitro assays or solely epidemiological studies could not be sufficient to explain the antioxidant activity of compounds in human body. At the end of the 1990s, it was noticed that there was little information about the extent of TOK-001 and metabolism of different antioxidant compounds and it was tried to elucidate mechanistic explanation to fully understand how these molecules behave in human physiological processes. For example, it was reported that the digestion and absorption of carotenoids and tocopherols, as lipid soluble antioxidants, involved several steps following as the breaking down of food matrix, release of carotenoids or tocopherols, dispersion in lipid emulsion, solubilization in micelles, movement across the unstirred water layer, uptake by enterocytes and incorporation into lymphatic lipoproteins (Furr and Clark, 1997, Rigotti, 2007). As water-soluble antioxidants, polyphenols were also of importance and the metabolism of phenolic compounds was investigated over a course of decades. In several studies, it was emphasized that in addition to amount of antioxidants intake from food, their biological properties might depend on their release from food matrix during digestion; therefore in vitro gastrointestinal model was developed to show their digestion behavior (Pérez-Jiménez and Saura-Calixto, 2005, Saura-Calixto et al., 2000, Serrano et al., 2005, Serrano et al., 2007). Serrano et al. (2007) compared the methods to determine the antioxidant activity of foods using in vitro physiological procedure with classical chemical extraction methods and several differences were found between two methods. According to in vitro studies combined with in vivo, it was enlightened that the metabolism of free phenolic compounds started in the small intestine followed by the absorption of bioavailable parts and their modifications in the liver or other organs (Manach, Williamson, Morand, Scalbert, & Remesy, 2005). Once ingested, phenolic compounds are metabolized and transformed into methylated, glucuronated and sulphated metabolites. Glucuronidation and sulfation conjugation reactions significantly reduce the polyphenols antioxidant activity, since both sulfation and glucuronidation occur at the reducing hydroxyl groups in the phenolic structure (Heleno, Martins, Queiroz, & Ferreira, 2015). It was thought that the chemical structure of polyphenols determined their rate and extent of intestinal absorption in addition to nature of their metabolites in plasma. For example, it was proved that the absorption rates of some flavonoids quercetin and rutin were low, although catechins in green tea, isoflavones in soy, flavanones in citrus fruits or anthocyanidins in red wine showed high absorption capacity (Cao et al., 1998, Scalbert and Williamson, 2000). It was reported that although the ingestion of green tea or catechins had high absorption capacity and caused rapid increase in plasma antioxidant capacity in nanomolar levels, its effect depleted within 2h (Benzie et al., 1999, Rein et al., 2000). On the other hand, it was revealed that flavonoids bound to sugar molecules such as quercetin glycosides firstly broke down via some enzymes (β-glucosidase) in the small intestine followed by releasing of flavonoid skeleton (aglycone) (Donovan et al., 2007, Hollman and Katan, 1999). Numerous studies have also shown that the acidic or enzymatic digestion might not affect the strongly bound antioxidant to food matrix, so they reached colon and became available to metabolize by colon microbiota. After that, in vitro colonic fermentation method was also developed to elucidate what happened to the antioxidants in human gut (Goñi & Martin-Carrón, 2001). It was reported that three possible routes were available in the colon: (1) absorption of antioxidant through colonic epithelium and passage into the blood stream (Rios et al., 2003); (2) breakdown of the antioxidants to the metabolites (Jenner, Rafter, & Halliwell, 2005); (3) creating the reducing environment in the colon where they might counteract the oxidant or toxic species (Serrano et al., 2007).