Immune Cells Activity, Pharmacokinetics After Oral Intake, Safety After Oral Intake
Conditions
Keywords
Bioavailability, Pharmacokinetics, 8-prenylnaringenin, 6-prenylnaringenin, Prenylflavonoids, PBMC
Brief summary
The prenylflavonoids 6-prenylnaringenin (6-PN) and 8-prenylnaringenin (8-PN) are secondary plant substances, almost exclusively found in hops (Humulus lupulus). Both compounds have known potential biological properties, but poor bioavailability due to their low oral absorption and retention. Our study followed a single dose (500 mg 6- or 8-PN), placebo controlled, randomized, double-blind, three armed crossover study design with ≥2-week washout periods. Plasma, PBMC and urine samples were collected at intervals up to 24 h after intake. Investigators investigated the safety, pharmacokinetics and impact of oral prenylflavonoids on the function of cells of the immune system.
Interventions
DIETARY_SUPPLEMENTPlacebo
DIETARY_SUPPLEMENT6-prenylnaringenin
DIETARY_SUPPLEMENT8-prenylnaringenin
Sponsors
Universität Tübingen
University of Hohenheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy Volunteers with blood chemistry values within normal ranges * Age: 18-45 years * BMI: 19-25 kg/m2
Exclusion criteria
* Pregnancy or lactation * Alcohol and/or drug abuse * Use of dietary supplements or any medications, except contraceptives * Any known malignant, metabolic and endocrine diseases * Previous cardiac infarction * Dementia * Participation in a clinical trial within the past 6 weeks prior to recruitment * Physical activity of more than 5 h/wk
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean area under the curve (AUC) of plasma concentration vs. time of total 6-prenylnaringenin [nmol/L*h] | 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose | Total 6-PN after deconjugation with beta-glucuronidase/sulphatase |
| Mean area under the curve (AUC) of plasma concentration vs. time of total 8-prenylnaringenin [nmol/L*h] | 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose | Total trans-epsilon-viniferin after deconjugation with beta-glucuronidase/sulphatase |
| Mean maximum plasma concentration (Cmax) of total 6-prenylnaringenin [nmol/L] | 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose | Total trans-resveratrol after deconjugation with beta-glucuronidase/sulphatase |
| Mean maximum plasma concentration (Cmax) of total 8-prenylnaringenin [nmol/L] | 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose | Total trans-epsilon-viniferin after deconjugation with beta-glucuronidase/sulphatase |
| Time to reach maximum plasma concentration (Tmax) of total 6-prenylnaringenin [h] | 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose | Total trans-resveratrol after deconjugation with beta-glucuronidase/sulphatase |
| Time to reach maximum plasma concentration (Tmax) of total 8-prenylnaringenin [h] | 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose | Total trans-epsilon-viniferin after deconjugation with beta-glucuronidase/sulphatase |
| Cumulative urinary excretion of total 6-prenylnaringenin [nmol/g creatinine] | 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose | Total trans-resveratrol after deconjugation with beta-glucuronidase/sulphatase |
| Cumulative urinary excretion of total 8-prenylnaringenin [nmol/g creatinine] | 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose | Total trans-epsilon-viniferin after deconjugation with beta-glucuronidase/sulphatase |
| Cell count (dead cells/ml and living cells/ml) of PBMCs after 6-PN administration | 0, 6, and 24 h post dose | — |
| Cell count (dead cells/ml and living cells/ml) of PBMCs after 8-PN administration | 0, 6, and 24 h post dose | — |
| Cell viability of PBMCs after 6-PN administration | 0, 6, and 24 h post dose | — |
| Cell viability of PBMCs after 8-PN administration | 0, 6, and 24 h post dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Serum cystatin C [mg/mL] | 0, 4, 24h post-dose |
| Glomerular filtration rate [mL/min] | 0, 4, 24h post-dose |
| Serum glucose [mg/dL] | 0, 24h post-dose |
| Hemoglobin [g/dL] | 0, 24h post-dose |
| Mean corpuscular hemoglobin concentration [g/dL] | 0, 24h post-dose |
| Mean corpuscular hemoglobin [pg] | 0, 24h post-dose |
| Mean corpuscular volume [fL] | 0, 24h post-dose |
| Hematocrit [%] | 0, 24h post-dose |
| Serum aspartate transaminase activity [U/L] | 0, 4, 24h post-dose |
| Thrombocytes [/nL] | 0, 24h post-dose |
| Leucocytes [/nL] | 0, 24h post-dose |
| Segmented granulocytes [%] | 0, 24h post-dose |
| Lymphocytes [%] | 0, 24h post-dose |
| Monocytes [%] | 0, 24h post-dose |
| Basophil granulocytes [%] | 0, 24h post-dose |
| Eosinophil granulocytes [%] | 0, 24h post-dose |
| Erythrocytes [/pL] | 0, 24h post-dose |
| Serum alanine transaminase activity [U/L] | 0, 4, 24h post-dose |
| Serum gamma-glutamyl transferase activity [U/L] | 0, 4, 24h post-dose |
| Serum alkaline phosphatase activity [U/L] | 0, 4, 24h post-dose |
| Serum bilirubin | 0, 4, 24h post-dose |
| Serum uric acid [mg/dL] | 0, 4, 24h post-dose |
| Serum creatinine [mg/dL] | 0, 4, 24h post-dose |
| Serum total cholesterol [mg/dL] | 0, 4, 24h post-dose |
| Serum HDL cholesterol [mg/dL] | 0, 4, 24h post-dose |
| Serum LDL cholesterol [mg/dL] | 0, 4, 24h post-dose |
| Serum triacylglycerols [mg/dL] | 0, 4, 24h post-dose |
| LDL/HDL cholesterol ratio | 0, 4, 24h post-dose |
Countries
Germany
Outcome results
None listed