Ispitivanje učinka ekstrakta planike (Arbutus unedo L.) na enzimsku aktivnost CYP2C8

master's thesis

• Title (english): Assessment of the effect of strawberry tree (Arbutus unedo L.) extract on CYP2C8 enzyme activity
• Author: Marija Škrlec
• Mentor: Mirza Bojić (mentor)
• Committee member: Mirza Bojić (predsjednik povjerenstva)
• Committee member: Kristina Pavić (član povjerenstva)
• Committee member: Hrvoje Rimac (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medicinal chemistry); Zagreb
• Defense date and country: 2020-05-05, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Arbutus unedo L. ili planika je biljka koja raste u mediteranskom podrucju, a njeni listovi koriste se kao urinarni
antiseptik, antidijaroik, adstringens, purgativ, antioksidans, antihipertenziv, antitrombotik i protuupalna tvar.
Biljka je bogata raznim spojevima, poput fenolnih kiselina, trjeslovina, masnih kiselina, vitamina E i C, [3-
karotena, triterpena, iridoida, etericnog ulja, secera, organskih kiselina i flavonoida. Zadnje navedena skupina
spojeva odgovoma je za pozitivne ucinke u ljudskom tijelu. Radi se o polifenolnim spojevima koji su inace
prisutni i u velikom broju drugih biljaka te u biljnim proizvodima. Iako su flavonoidi pokazali brojne pozitivne
ucinke na ljudsko tijelo, oni takoder mogu utjecati na enzimsku aktivnost metabolickih enzima zaduzenih za
biotransformaciju lijekova te na taj nacin interferirati s farmakoloskim ucinkom lijeka. Ponajprije se misli na
citokrom P450 enzime, zasluzne za oksidativnu biotransformaciju 96% lijekova, koji se vecinom nalaze u jetri.
Cilj ovog rada bio je utvrditi utjecaj metanolnih ekstrakata planike na enzimsku aktivnost CYP2C8. U tu svrhu
koristeno je 12 uzoraka planike skupljenih tijekom 12 mjeseci tijekom 2018. godine. Aktivnost CYP2C8 pracena
je primjenom paklitaksela kao marker supstrata koji se djelovanjem navedenog enzima prevodi u 6-
hidroksipaklitaksel. Nastali metabolit odreden je primjenom obmuto fazne tekucinske kromatografije visoke
djelotvomosti spregnute s UV detekcijom. Rezultat je iskazan kao postotak nastalog metabolita u odnosu na
kontrolu bez inhibitora. Svi ispitani uzorci inhibirali su nastanak 6-hidroksipaklitaksela te je preostala enzimska
aktivnost iznosila od 27% do 54%. Rezultati ukazuju da ekstrakti planike mogu utjecati na enzimsku aktivnost
CYP2C8, a temeljem usporedbe s kemijskim sastavom ekstrakata ucinak se djelomicno moze povezati s
polifenolnim sastavnicama ekstrakta planike.

Abstract (english)

Arbutus unedo L. or strawberry tree is a plant that grows in the Mediterranean area and its leaves of the plant are used
as urinary antiseptic, antidiarrheal, astringent, purgative, antioxidant, antihypertensive, antithrombotic and antiinflammatory
substance. The plant is rich in various compounds, such as phenolic acids, tannins, fatty acids, vitamins
E and C, 􀁛-carotene, triterpene, iridoids, essential oils, sugars, organic acids and flavonoids. The latter group of
compounds is responsible for the positive effects in the human body. Flavonoids are polyphenolic compounds that are
otherwise present in many other plants and plant products. Although they have shown numerous positive effects in
the human body, they can also interact with certain enzymes responsible for drug metabolism and thus interfere with
the pharmacological effect of the drug. This primarily refers to cytochrome P450 enzymes, responsible for oxidative
biotransformation of 96% of drugs.
The aim of this study was to determine the influence of methanolic extracts of strawberry tree on CYP2C8 enzymatic
activity. For this purpose, 12 samples of the plant collected over 12 months during 2018 were used. CYP2C8 activity
was monitored by the use of paclitaxel as a marker substrate, which is converted to 6-hydroxypaclitaxel by the enzyme.
The resulting metabolite was determined using high performance reverse phase liquid chromatography coupled with
a UV detection. The result is expressed as the percentage of metabolite produced relative to the control without
inhibitors. All samples tested inhibited the formation of 6-hydroxypaclitaxel and the residual enzyme activity ranged
from 27% to 54%. The results indicate that strawberry tree extracts can influence the enzymatic activity of CYP2C8,
and on the basis of comparison with the chemical composition of the extracts, the effect can be partially related to the
polyphenolic constituents of strawberry tree extract.

• Keywords: Arbutus unedo; flavonoidi; citokrom P450; HPLC
• Keywords (english): Arbutus unedo; flavonoids; cytochrome P450; HPLC
• Language: croatian
• URN:NBN: urn:nbn:hr:163:082651
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Reformatted digital
• Access conditions: Open access
• Created on: 2022-08-29 11:08:50