Anthocyans are biologically active constituents of various berry fruits and they are also contained in nutritional supplements derived from extracts or dry matter from berry fruits. In this study we evaluated the effects of anthocyans on the expression of selected drug-metabolizing phase II genes in primary cultures of human hepatocytes by qRT-PCR. Most of the tested anthocyanidins (6) and anthocyanins (21) did not induce the expression of mRNA of UGT1A/2B members in human hepatocytes. The same can be stated for expression of selected GST genes on the mRNA level. However, some of them e.g. cyanidin-3-O-rutinoside consistently decreased the level of GSTP1 mRNA in all tested cultures. In conclusion, most of the anthocyans did not affect the expression of selected phase II metabolizing enzymes in vitro.

• MeSH
• anthokyaniny farmakologie   MeSH
• glukuronosyltransferasa genetika   metabolismus   MeSH
• hepatocyty účinky léků   enzymologie   metabolismus   MeSH
• II. fáze biotransformace * MeSH
• kultivované buňky MeSH
• lidé MeSH
• xenobiotika metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anthokyaniny MeSH
• glukuronosyltransferasa MeSH
• xenobiotika MeSH

Anthocyanidins and anthocyanins are pharmacologically active constituents of various berry fruits, such as blueberry and cranberry. These compounds are also contained in massively used nutritional supplements based on extracts or dry matter from berry fruits. The current study evaluated the effects of anthocyanidins and anthocyanins on the expression and catalytic activity of major drug-metabolizing enzymes CYP2C9, CYP2A6, CYP2B6, and CYP3A4 in primary cultures of human hepatocytes and human liver microsomes. Expression of mRNA was quantified by qRT-PCR. Expression of proteins was evaluated by Western blotting and immunochemiluminescence. The catalytic activity of CYP enzymes was measured by HPLC using specific enzyme substrates. Tested anthocyanidins (6) and anthocyanins (21) did not induce the expression of mRNA and protein of CYP2C9, CYP2A6, CYP2B6, and CYP3A4 genes in human hepatocytes. Catalytic activities of CYP2C9, CYP2A6, CYP2B6, and CYP3A4 enzymes were inhibited by all anthocyanidins to different extents (e.g., delphinidin inhibits CYP3A4 by >90% at 100 μM with IC50 = 32 μM). Of 21 anthocyanins tested, only cyanidin-3-O-rhamnoside (CYP3A4 by >75% at 100 μM with IC50 = 44 μM) and two glycosides of delphinidin significantly inhibited examined cytochromes P450. It may be concluded that in the ranges of common ingestion of either food or dietary supplement an induction or significant inhibition of CYP2C9, CYP2A6, CYP2B6, and CYP3A4 activity is most probably not expected.

• Klíčová slova
• anthocyans, cytochrome P450, food−drug interactions, human hepatocytes, xenobiotics,
• MeSH
• anthokyaniny farmakologie   MeSH
• biokatalýza MeSH
• brusnice s jedlými plody chemie   MeSH
• cytochrom P-450 CYP3A genetika   metabolismus   MeSH
• cytochrom P450 CYP2B6 genetika   metabolismus   MeSH
• cytochrom P450 CYP2C9 genetika   metabolismus   MeSH
• hepatocyty enzymologie   MeSH
• jaterní mikrozomy enzymologie   MeSH
• lidé MeSH
• regulace genové exprese enzymů účinky léků   MeSH
• rostlinné extrakty farmakologie   MeSH
• Vaccinium macrocarpon chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anthokyaniny MeSH
• cytochrom P-450 CYP3A MeSH
• cytochrom P450 CYP2B6 MeSH
• cytochrom P450 CYP2C9 MeSH
• rostlinné extrakty MeSH

P-glycoprotein (P-gp) inhibition represents a promising therapeutic strategy for oncologic patients. The inhibition by naturally occurring anthocyans would bring certain benefits. Unfortunately, due to the low bioavailability and consequently low blood level, they cannot be used for cancer therapy. However, due to the food supplementation, significant concentration can raise up in the intestine, where P-gp is abundantly expressed. As many drugs are orally taken, simultaneous administration might affect the concentration of these drugs in the blood. Here, we found that anthocyanidins (aglycons) but not anthocyanins (glycosides) can significantly inhibit P-gp up to 60% of positive control, verapamil. This inhibitory activity was observed for 500 μm concentrations of malvidin and pelargonidin. We conclude that these compounds may be the source of food-drug interactions either for orally taken drugs or for intravenously administered drugs eliminated via biliary excretion which are the substrates of P-gp.

• Klíčová slova
• MDR1, calcein assay, inhibition, malvidin, pelargonidin,
• MeSH
• anthokyaniny aplikace a dávkování   metabolismus   MeSH
• aplikace orální MeSH
• fluoresceiny aplikace a dávkování   metabolismus   MeSH
• interakce mezi potravou a léky * fyziologie   MeSH
• lidé MeSH
• P-glykoprotein antagonisté a inhibitory   metabolismus   MeSH
• potravní doplňky * MeSH
• prasata MeSH
• verapamil aplikace a dávkování   metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anthokyaniny MeSH
• fluoresceiny MeSH
• fluorexon MeSH Prohlížeč
• P-glykoprotein MeSH
• verapamil MeSH

Foliar anthocyanins shape a peculiar shade in a red leaf's interior leading to uneven energy distribution between the two photosystems. Accordingly, a readjustment of PSII/PSI stoichiometry could restore excitation balance. To test this hypothesis, 77 K fluorescence emission spectra of thylakoids from green and red leaves of seven species with different pigment profiles were compared. The ratio of F686/F736 served as an indication of the PSII/PSI functional ratio. To avoid possible species-dependent differences in the measured parameters, plants showing intra-individual, intra-species, or intra-leaf variation in the expression of the anthocyanic character were used. Red leaves or red leaf areas displayed higher PSII/PSI ratio, irrespectively of species and anthocyanin accumulation pattern. PSII/PSI ratio declined in parallel with anthocyanin decrease. In five species, red leaves displayed also a lower Chl a/b ratio. We conclude that red leaves growing in full sunlight develop adaptive adjustments in their chlorophyll and photosystem ratios, compatible with the shade-acclimation syndrome.

• Klíčová slova
• fluorescence emission spectra, foliar anthocyanins, photosystem ratio, shade-acclimation syndrome,
• Publikační typ
• časopisecké články MeSH