Oral Bioavailability and Bioactivity of Prenylflavonoids From Hops

Study Overview
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Brief Summary
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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.

Official Title
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Examination of the Bioavailability and Bioactivity of the Two Natural Food Ingredients 6-Prenylnaringenin and 8-Prenylnaringenin.

Conditions
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Safety After Oral Intake, Pharmacokinetics After Oral Intake, Immune Cells Activity

Intervention / Treatment
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* Dietary Supplement: Placebo
* Dietary Supplement: 6-prenylnaringenin
* Dietary Supplement: 8-prenylnaringenin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Capsules filled with mannitol and silicon dioxide | Dietary Supplement: Placebo<br> <br> |
| Experimental: 6-prenylnaringenin<br>500 mg 6-PN plus mannitol and silicon dioxide | Dietary Supplement: 6-prenylnaringenin<br> <br> * Other names: 6-PN;|
| Experimental: 8-prenylnaringenin<br>500 mg 8-PN plus mannitol and silicon dioxide | Dietary Supplement: 8-prenylnaringenin<br> <br> * Other names: 8-PN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean area under the curve (AUC) of plasma concentration vs. time of total 6-prenylnaringenin [nmol/L*h] | Total 6-PN after deconjugation with beta-glucuronidase/sulphatase | 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose | 
| Mean area under the curve (AUC) of plasma concentration vs. time of total 8-prenylnaringenin [nmol/L*h] | Total trans-epsilon-viniferin after deconjugation with beta-glucuronidase/sulphatase | 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose | 
| Mean maximum plasma concentration (Cmax) of total 6-prenylnaringenin [nmol/L] | Total trans-resveratrol after deconjugation with beta-glucuronidase/sulphatase | 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose | 
| Mean maximum plasma concentration (Cmax) of total 8-prenylnaringenin [nmol/L] | Total trans-epsilon-viniferin after deconjugation with beta-glucuronidase/sulphatase | 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose | 
| Time to reach maximum plasma concentration (Tmax) of total 6-prenylnaringenin [h] | Total trans-resveratrol after deconjugation with beta-glucuronidase/sulphatase | 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose | 
| Time to reach maximum plasma concentration (Tmax) of total 8-prenylnaringenin [h] | Total trans-epsilon-viniferin after deconjugation with beta-glucuronidase/sulphatase | 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose | 
| Cumulative urinary excretion of total 6-prenylnaringenin [nmol/g creatinine] | Total trans-resveratrol after deconjugation with beta-glucuronidase/sulphatase | 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose | 
| Cumulative urinary excretion of total 8-prenylnaringenin [nmol/g creatinine] | Total trans-epsilon-viniferin after deconjugation with beta-glucuronidase/sulphatase | 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum aspartate transaminase activity [U/L] |  | 0, 4, 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 | 
| 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 | 
| Erythrocytes [/pL] |  | 0, 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bioavailability, Pharmacokinetics, 8-prenylnaringenin, 6-prenylnaringenin, Prenylflavonoids, PBMC