Juho Hokkanen

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Self-administration of complementary products concurrently with conventional medication is increasingly common. The potential for cytochrome P450 (CYP) inhibition requires investigation. The N-in-one assay with ten probe substrates for nine CYPs was used with human liver microsomes to investigate ten products. CYP inhibition was measured in a single liquid(More)
Phenolic compounds from leaves of lingonberry (Vaccinium vitis-idaea L.), bilberry (Vaccinium myrtillus L.), and the natural hybrid of bilberry and lingonberry (Vaccinium x intermedium Ruthe L., hybrid bilberry) were identified using LC/TOF-MS and LC/MS/MS after extraction from the plant material in methanol in an ultrasonicator. The phenolic profiles in(More)
The TET enzymes are members of the 2-oxoglutarate-dependent dioxygenase family and comprise three isoenzymes in humans: TETs 1-3. These TETs convert 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC) in DNA, and high 5-hmC levels are associated with active transcription. The importance of the balance in these modified cytosines is emphasized by the fact(More)
Hypericins are biologically active constituents of Hypericum perforatum (St John's wort). It is likely that emodin anthrone, an anthraquinone precursor of hypericins, is biosynthesized via the polyketide pathway by type III polyketide synthase (PKS). A PKS from H. perforatum, HpPKS2, was investigated for its possible involvement in the biosynthesis of(More)
The effect of oral contraceptives (OCs) on melatonin metabolism was studied in 29 subjects genotyped for CYP1A2 SNP g.-163C>A polymorphism. Plasma melatonin and 6-OH-melatonin concentrations were measured after a 6-mg dose of melatonin using a validated liquid chromatography/mass spectrometry method. The mean melatonin AUC and C(max) values were 4- to(More)
Bilberry (Vaccinium myrtillus) represents one of the richest flavonoid sources among plants. Flavonoids play variable, species-dependent roles in plant defences. In bilberry, flavonoid metabolism is activated in response to solar radiation but not against mechanical injury. In this paper, the defence reaction and biosynthesis of phenolic compounds of(More)
The metabolism of hyperforin, one of the pharmacologically most active components of St. John's wort (Hypericum perforatum), was characterized in vitro using human liver microsomes and recombinant heterologously expressed P450 enzymes. A total of 57 hyperforin metabolites were detected. Of those, six were identified as monohydroxylations (M1-M6), while the(More)
This study determined the unbound fraction of the peripheral α2 -adrenoceptor antagonist MK-467 alone and combined with medetomidine. MK-467 (0.1, 1 and 10 μm) was incubated in canine plasma with and without medetomidine (molar ratio 20:1), with human serum albumin (HSA) and with α1-acid glycoprotein (AGP). Rapid equilibrium dialysis was used for the(More)
In vitro methods to produce metabolic information have increasingly been applied in toxicity risk assessment. In the current contract project of JRC/ECVAM In vitro-Toxicology Unit, 55 organic chemicals, mostly drugs and pesticides, most belonging to ECVAM/ICCVAM validation compounds, expected to be analyzable by LC-MS technique, were subjected to a(More)
Although several in vitro models have been reported to predict the ability of drug candidates to cross the blood-brain barrier, their real in vivo relevance has rarely been evaluated. The present study demonstrates the in vivo relevance of simple unidirectional permeability coefficient (P(app)) determined in three in vitro cell models (BBMEC, Caco-2 and(More)