Abstract
Enterolactone (EL) is a gut microbe metabolite of the flaxseed lignan secoisolariciresinol diglucoside (SDG). Studies suggest a correlation between EL systemic levels and protective effects against cancer and cardiovascular disease. EL's oral bioavailability is low and highly variable due to extensive first-pass metabolism. To better understand the contribution of liver and intestine to first-pass glucuronidation we conducted an in vitro enzyme kinetic analysis of EL glucuronidation in liver and intestinal microsomes from both human and rat. An intrinsic clearance (CLint) value was calculated using the substrate depletion approach. In addition to monitoring substrate depletion, HPLC analysis allowed detection of EL glucuronides which were further substantiated by LC-MS/MS. EL monoglucuronide was identified in human and rat liver and intestinal microsomes. Enzyme kinetic studies indicated the extent of hepatic microsomal glucuronidation exceeded intestinal glucuronidation in both human and rat, while the human liver CLint value was slightly higher than that of rat liver. The CLint value generated in human intestinal microsomes was only one third of human liver, whereas the CLint of rat jejunum or colon was one-twentieth of rat liver suggesting the human intestine makes a greater contribution to EL glucuronidation than rat intestine. Our results suggest that both liver and intestine contribute to EL glucuronidation and the human intestine may exert a greater influence on the first-pass glucuronidation of EL than rat intestine. The rat might underestimate the extent of intestinal metabolism of EL relative to human.
Keywords: Enterolactone, flaxseed, glucuronidation, intestine, liver, lignan.
The Natural Products Journal
Title:The Comparison of Rat and Human Intestinal and Hepatic Glucuronidation of Enterolactone Derived from Flaxseed Lignans
Volume: 3 Issue: 3
Author(s): Chaojie Lin, Ed S Krol and Jane Alcorn
Affiliation:
Keywords: Enterolactone, flaxseed, glucuronidation, intestine, liver, lignan.
Abstract: Enterolactone (EL) is a gut microbe metabolite of the flaxseed lignan secoisolariciresinol diglucoside (SDG). Studies suggest a correlation between EL systemic levels and protective effects against cancer and cardiovascular disease. EL's oral bioavailability is low and highly variable due to extensive first-pass metabolism. To better understand the contribution of liver and intestine to first-pass glucuronidation we conducted an in vitro enzyme kinetic analysis of EL glucuronidation in liver and intestinal microsomes from both human and rat. An intrinsic clearance (CLint) value was calculated using the substrate depletion approach. In addition to monitoring substrate depletion, HPLC analysis allowed detection of EL glucuronides which were further substantiated by LC-MS/MS. EL monoglucuronide was identified in human and rat liver and intestinal microsomes. Enzyme kinetic studies indicated the extent of hepatic microsomal glucuronidation exceeded intestinal glucuronidation in both human and rat, while the human liver CLint value was slightly higher than that of rat liver. The CLint value generated in human intestinal microsomes was only one third of human liver, whereas the CLint of rat jejunum or colon was one-twentieth of rat liver suggesting the human intestine makes a greater contribution to EL glucuronidation than rat intestine. Our results suggest that both liver and intestine contribute to EL glucuronidation and the human intestine may exert a greater influence on the first-pass glucuronidation of EL than rat intestine. The rat might underestimate the extent of intestinal metabolism of EL relative to human.
Export Options
About this article
Cite this article as:
Lin Chaojie, Krol S Ed and Alcorn Jane, The Comparison of Rat and Human Intestinal and Hepatic Glucuronidation of Enterolactone Derived from Flaxseed Lignans, The Natural Products Journal 2013; 3 (3) . https://dx.doi.org/10.2174/2210315511303030001
DOI https://dx.doi.org/10.2174/2210315511303030001 |
Print ISSN 2210-3155 |
Publisher Name Bentham Science Publisher |
Online ISSN 2210-3163 |
Call for Papers in Thematic Issues
Ayurvedic medicinal therapeutic approaches for inflammatory and neurodegenerative disorders
Usually, in our elderly population, neurodegenerative disorders occur due to neuron death. Alzheimer?s disease (AD) is an irreversible and progressive neurodegenerative disease. Dementia is the leading cause of AD, which affects about 30 million people worldwide. According to the World Alzheimer report 2018, a new case of dementia develops every ...read more
Recent Advances in Biotransformation of Bioactive Terpenoids using Aspergillus niger
Biotransformation is the reaction catalyzed by biological catalysts of either isolated enzymes or whole cell cultures of microorganisms. This process has been extensively applied in the conversion of bioactive terpenoids with high regio- and stereospecifity. This process has been also applied in the lead discovery and development. Aspergillus niger has ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Current Pharmacologic Management of Pediatric Heart Failure in Congenital Heart Disease
Current Vascular Pharmacology Relationship between SNP rs1764391 and Susceptibility, Risk Factors, Gene-environment Interactions of Acute Myocardial Infarction in Guangxi Han Chinese Population
Current Pharmaceutical Biotechnology Current Role and Future Perspectives of Radioiodinated MIBG in the Evaluation of Dementia with Lewy Bodies
Current Radiopharmaceuticals Expanding the Therapeutic Potential of Statins by Means of Nanotechnology Enabled Drug Delivery Systems
Current Topics in Medicinal Chemistry Polyunsaturated Fatty Acids and Cardiovascular Disease
Current Pharmaceutical Design Long-Term Multimodal Therapy (Verapamil Associated with Propolis, Blueberry, Vitamin E and Local Diclofenac) on Patients with Peyronie's Disease (Chronic Inflammation of the Tunica Albuginea). Results of a Controlled Study
Inflammation & Allergy - Drug Targets (Discontinued) Prolyl Hydroxylase Domain-2 Silencing Induced by Hydrodynamic Limb Vein Injection Enhances Vascular Regeneration in Critical Limb Ischemia Mice through Activation of Multiple Genes
Current Gene Therapy Targeting Resveratrol to Mitochondria for Cardiovascular Diseases
Recent Patents on Cardiovascular Drug Discovery Micro- and Macrovascular Treatment Targets in Scleroderma Heart Disease
Current Pharmaceutical Design Metabolic Syndrome, Thyroid Function and Autoimmunity - The PORMETS Study
Endocrine, Metabolic & Immune Disorders - Drug Targets Tofacitinib, an Oral Janus Kinase Inhibitor: Perspectives in Dermatology
Current Medicinal Chemistry Pathogenetic Pathways of Cardiorenal Syndrome and their Possible Therapeutic Implications
Current Pharmaceutical Design Benefits of SGLT2 Inhibitors Beyond Glycemic Control – A Focus on Metabolic, Cardiovascular and Renal Outcomes
Current Diabetes Reviews Screening of Antioxidant, Antimicrobial Activities and Chemical Contents of Edible Mushrooms Wildly Grown in the Black Sea Region of Turkey
Combinatorial Chemistry & High Throughput Screening Flavonoids Health Benefits and Their Molecular Mechanism
Mini-Reviews in Medicinal Chemistry Cardioprotective Activity of Agaricus bisporus Against Isoproterenol- Induced Myocardial Infarction in Laboratory Animals
Current Nutrition & Food Science Antioxidant Effects of Natural Bioactive Compounds
Current Pharmaceutical Design Oxaliplapin and Capecitabine (XELOX) Based Chemotherapy in the Treatment of Metastatic Colorectal Cancer: The Right Choice in Elderly Patients
Anti-Cancer Agents in Medicinal Chemistry The Bioactive Compounds Obtained from Hawthorn, Chokeberry, Rosehip and Bilberry by Microfiltration
Current Bioactive Compounds Cardiac Applications for Human Pluripotent Stem Cells
Current Pharmaceutical Design