![]() Human serum albumin (HSA) has a major role in the transport of several drugs and xenobiotics in the human circulation. Ĭhemical structures of resorcinol (RES), 4-methylcatechol (4MC), pyrogallol (PYR), phloroglucinol (PHLO), benzoic acid (BA), 4-hydroxybenzoic acid (4HBA), 2,4-dihydroxybenzoic acid (24DHBA), 2-hydroxy-4-methoxybenzoic acid (2H4MBA), 3,4-dihydroxybenzoic acid (34DHBA), 2,4-dihydroxyacetophenone (24DHAP), 2-hydroxyphenylacetic acid (2HPAA), 4-hydroxyphenylacetic acid (4HPAA), 3,4-dihydroxyphenylacetic acid (34DHPAA), 3-hydroxy-4-methoxyphenylacetic acid (3H4MPAA), 3-methoxy-4-hydroxyphenylacetic acid (3M4HPAA), 4-(hydroxymethyl)phenylacetic acid (4HMPAA), 3-phenylpropionic acid (3PPA), 3-(3-hydroxyphenyl)propionic acid (33HPPA), 3-coumaric acid (3CA), 3-(4-hydroxyphenyl)propionic acid (34HPPA), 3-(2,4-dihydroxyphenyl)propionic acid (324DHPAA), 3-(3,4-dihydroxyphenyl)propionic acid (334DHPPA), O-desmethylangolensin (DESMA), and hippuric acid (HIPA). As to pharmacokinetic issues, some colonic metabolites were previously shown to interact with serum albumin or biotransformation enzymes, such as pyrogallol (PYR) which form a stable complex with albumin, and it is a potent inhibitor of xanthine oxidase enzyme. For example, 3-hydroxyphenylacetic, 3-methoxy-4-hydroxyphenylacetic and 3,4-dihydroxyphenylacetic acids were identified as the major colonic metabolites of quercetin, after the oral administration of quercetin-3-rutinoside to healthy human subjects. Typically, the microbial metabolites of flavonols are phenylacetic and phenylpropionic acids, while flavones and flavanones are biotransformed into phenylpropionic acids (then to benzoic acid). The colonic metabolites can be classified as hydroxybenzoic, hydroxyacetic and hydroxycinnamic acids, and hydroxybenzenes ( Figure 1). A large fraction of flavonoids, not absorbed from the small intestines, can be biotransformed by the colon microbiota, leading to the degradation of flavonoid ring(s) to smaller phenolic compounds. In general, flavonoid aglycones are extensively conjugated even in enterocytes and later in hepatocytes, resulting in the production of methyl, sulfate, and glucuronide metabolites. The oral bioavailability of parent flavonoids is low due to their physicochemical properties and high presystemic elimination. Therefore, the high intake of flavonoids may cause pharmacokinetic interactions with clinically used drugs, as has been reviewed in several papers. Furthermore, flavonoids can interact with proteins involved in drug pharmacokinetics, such as serum albumin, biotransformation enzymes, and drug transporters. Some of these dietary supplements contain extremely high doses of flavonoids (ranging from several hundreds to thousands of milligrams). Therefore, flavonoid-containing dietary supplements are widely marketed through the Internet. Our results demonstrate that, besides flavonoid aglycones and their conjugated derivatives, some colonic metabolites are also able to interact with proteins involved in the pharmacokinetics of drugs.įlavonoids, phenolic compounds found in numerous plants (including fruits and vegetables), have been demonstrated to have beneficial health effects in several in vitro and in vivo studies. Furthermore, resorcinol and phloroglucinol showed strong inhibitory effects on CYP3A4. All CYP isoforms examined were significantly inhibited by O-desmethylangolensin nevertheless, only its effect on CYP2C9 seems to be relevant. ![]() ![]() However, the compounds tested did not considerably displace Site I and II marker drugs from albumin. Our results demonstrated that some metabolites (e.g., 2,4-dihydroxyacetophenone, pyrogallol, O-desmethylangolensin, and 2-hydroxy-4-methoxybenzoic acid) form stable complexes with albumin. Therefore, in this in vitro study, we investigated the interactions of 24 microbial flavonoid metabolites with human serum albumin and cytochrome P450 (CYP2C9, 2C19, and 3A4) enzymes. Despite the fact that several colonic metabolites appear in the circulation at high concentrations, we have only limited information regarding their pharmacodynamic effects and pharmacokinetic interactions. However, bacterial microflora in the human intestines also metabolize flavonoids, resulting in the production of smaller phenolic fragments (e.g., hydroxybenzoic, hydroxyacetic and hydroxycinnamic acids, and hydroxybenzenes). They are extensively biotransformed in enterocytes and hepatocytes, where conjugated (methyl, sulfate, and glucuronide) metabolites are formed. ![]() Flavonoids are abundant polyphenols in nature. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |