Metabolism of flavonoids mediated by cytochrome P450 1A2

Flavonoidi su velika grupa sekundarnih metabolita biljaka, a poznati su po svojim pozitivnim učincima na zdravlje. Osnovna struktura flavonoida sačinjena je od dva benzenska prstena povezana s heterocikličkim piranskim prstenom. Veliki broj spojeva flavonoida proizlazi iz supstitucije osnovnog flavonoidnog kostura s različitim kombinacijama višestrukih hidroksi i metoksi skupina. Većina ljudi svakodnevno je izložena flavonoidima pa je njihov utjecaj na ljudsko zdravlje važan. Dokazano je da imaju antibakterijsko, antivirusno, hepatoprotektivno, antitrombotsko i protuupalno djelovanje, a najbolje je istraženo njihovo antioksidativno svojstvo. Iako flavonoidi osiguravaju brojne povoljne učinke na zdravlje, oni su ksenobiotici pa ih je potrebno primjenjivati s određenim oprezom. Metabolizam flavonoida ide preko faze 1 i faze 2 biotransformacije kao i kod drugih ksenobiotika, na primjer lijekova. U fazi 1 metabolizma ksenobiotika ključnu ulogu ima citokrom P450, a pokazalo se da citokrom P450 1A2 (CYP1A2) ima glavnu ulogu u hidroksilaciji i demetilaciji flavonoida. Ovaj rad baziran je na istraživanju metabolizma flavonoida posredovanog s CYP1A2 kako bi proširili znanja o metabolizmu i metabolitima. Ispitan je metabolizam 11 flavonoida, a za pronalazak metabolita tih flavonoida korištena je tekućinska kromatografija spregnuta sa spektrometrijom masa (LC/MS) i UV-VIS detektor. Metaboliti su pronađeni kod 9 ispitanih flavonoida čime je dokazano da je u njihov metabolizam uključen CYP1A2 enzim. Važnost ove informacije leži u tome što flavonoidi i mnogi prepisani lijekovi dijele metaboličke procese faze 1 i faze 2 te je moguće da flavonoidi u određenoj mjeri utječu na metabolizam lijekova i potrebu za promjenom doziranja istih.Flavonoids are a large group of secondary metabolites of plants known for their beneficial effects on human health. Their structure is based on two benzene rings linked with a heterocyclic pyrane ring. The large number of flavonoid compounds is made from various combinations of substitution of the basic flavonoid skeleton with multiple hydroxyl and methoxyl groups. Humans are exposed to flavonoids on a daily basis and their impact on human health is of relevance. They have been found to have antimicrobial, antiviral, antihepatotoxic , antiplatelet and anti-inflammatory activities, but the best described property is antioxidant capacity. Although flavonoids provide numerous beneficial properties to human health, they are xenobiotics, so they have to be used with caution. Metabolism of flavonoids goes via phase 1 and phase 2 biotransformation, which is similar to other xenobiotics such as drugs. Cytochrome P450 play a key role in phase 1 metabolism of xenobiotics and it has been shown that cytochrome P450 1A2 (CYP1A2) has a major role in hydroxylation and demethylation of flavonoids. This thesis is based on research of flavonoids metabolism mediated by CYP1A2 for the purpose of expanding knowledge about flavonoid metabolism and metabolites. In this study, the interest was focused on metabolism of 11 flavonoids mediated by CYP1A2. Liquid chromatography mass spectrometry (LC/MS) and UV-VIS detector was used to found the metabolites of flavonoids. Of the 11 analysed flavonoids, 9 showed the tendency of biotransformation which proves the presence of enzyme CYP1A2 in their metabolism. This is important information because the flavonoids and many prescribed medications share phase 1 and phase 2 metabolic processes. Therefore, it is possible that flavonoids have an effect on drug metabolism and dosing amounts