抄録
This article discusses the absorption and metabolism of polyphenols, focusing on the glycosides of quercetin, a representative flavonoid, and the effects of side chain structure and hydrophilicity/hydrophobicity on bioavailability.
Most flavonoids are O-glycosides in which a sugar chain is β-linked to a phenolic hydroxyl group. Only a small proportion of flavonoid glycosides are absorbed in their original form after ingestion; most are hydrolyzed before absorption and/or further catabolized by intestinal microbiota. It is known that the site of absorption in the digestive tract differs depending on the number and type of sugar chains attached to O-glycosides. The stomach is an important site for anthocyanin absorption in their intact glycoside form. Flavonoid glycosides other than anthocyanins do not undergo structural changes in the stomach and are transported to the small intestine. Lactase hydrolyzes O-monoglucosides with various flavonoid backbones. In addition to the LPH pathway, it has also been reported that glucosides are taken up into the enterocytes as substrates of the sodium-glucose cotransporter (SGLT1) and then hydrolyzed by cytosolic β-glucosidase.
Glycosides other than monoglucosides are transported intact to the distal intestine, where they undergo metabolism by intestinal microbiota. The contribution of microbial degradation and enterohepatic circulation may exceed the influence of LPH expression. Flavonoid C-glycosides are poorly absorbed in the small intestine because they are not hydrolyzed; however, some are absorbed intact as glycosides.
Monoglucosides exhibit higher polarity than their aglycone forms after sugar removal, yet their polarity is not enough to dissolve readily in aqueous solutions. Industrially, molecules with enhanced water solubility are produced by enzymatically modifying the glycoside side chain, namely, removing β-linkages and then modifying the sugar chain with α-glucoside linkages that can be hydrolyzed by digestive enzymes in the body. Enzymatically modified isoquercitrin is one such example, and we have shown that it promotes the absorption of quercetin.
Polyphenols exist in the body as various conjugated metabolites. Flavonoid conjugates produced in the small intestine are mainly transported to the liver via the portal vein. Quercetin metabolites are not localized to lipoproteins in plasma. We have reported that flavonoids appear in lymphatic fluid after gastric and intestinal absorption. They exist in lymphatic fluid as highly water-soluble conjugates similarly to plasma, and are not incorporated into chylomicrons, unlike fat-soluble substances that are generally transported to the lymphatic system. However, due to their affinity for liposome membranes, conjugates may interact with the surfaces of lipoproteins such as chylomicrons in lymph and LDL in plasma.
To date, the physiological significance of lymphatic transport of flavonoids has not been elucidated. It is known that lymphatic transport functions as a pathway for delivering drug molecules with less metabolic change to peripheral tissues by bypassing the first-pass metabolic process in the liver. If lymphatic transport reduces the complex conjugates produced in the liver, it may facilitate flavonoid activity regulation through deconjugation. Since simultaneous administration with lipids promotes lymphatic transport of polyphenols, modifications that increase hydrophobicity, such as prenylation, can be expected to further promote lymphatic transport.
