Ligand Binding Affinities of Arctigenin and Its Demethylated Metabolites to Estrogen Receptor Alpha

Phytoestrogens are defined as plant-derived compounds with estrogen-like activities according to their chemical structures and activities. Plant lignans are generally categorized as phytoestrogens. It was reported that (−)-arctigenin, the aglycone of arctiin, was demethylated to (−)-dihydroxyenterolactone (DHENL) by Eubacterium (E.) sp. ARC-2. Through stepwise demethylation, E. sp. ARC-2 produced six intermediates, three mono-desmethylarctigenins and three di-desmethylarctigenins. In the present study, ligand binding affinities of (−)-arctigenin and its seven metabolites, including DHENL, were investigated for an estrogen receptor alpha, and found that demethylated metabolites had stronger binding affinities than (−)-arctigenin using a ligand binding screen assay method. The IC50 value of (2R,3R)-2-(4-hydroxy-3-methoxybenzyl)-3-(3,4-dihydroxybenzyl)-butyrolactone was 7.9 × 10−4 M.

• Publication year

  2013

• Venue

  Molecules

• Publication date

  2013-01-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.3390/molecules18011122PMID 23325100PMCID 6269892
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Transformation of trachelogenin, an aglycone of tracheloside from safflower seeds, to phytoestrogenic (−)-enterolactone by human intestinal bacteria

  2012cited by this paper
• A new mammalian lignan precursor, asarinin

  2011cited by this paper
• Human intestinal bacterium, strain END-2 is responsible for demethylation as well as lactonization during plant lignan metabolism.

  2010cited by this paper
• Further studies on a human intestinal bacterium Ruminococcus sp. END-1 for transformation of plant lignans to mammalian lignans.

  2009cited by this paper
• Receptor binding and transactivation activities of red clover isoflavones and their metabolites.

  2008cited by this paper
• Enantioselective oxidation of enterodiol to enterolactone by human intestinal bacteria.

  2007cited by this paper
• Clostridium saccharogumia sp. nov. and Lactonifactor longoviformis gen. nov., sp. nov., two novel human faecal bacteria involved in the conversion of the dietary phytoestrogen secoisolariciresinol diglucoside.

  2007cited by this paper
• Enantioselective dehydroxylation of enterodiol and enterolactone precursors by human intestinal bacteria.

  2007cited by this paper
• Isolation and characterization of a human intestinal bacterium, Eubacterium sp. ARC-2, capable of demethylating arctigenin, in the essential metabolic process to enterolactone.

  2007influential reference
• Phylogeny of human intestinal bacteria that activate the dietary lignan secoisolariciresinol diglucoside.

  2006cited by this paper
• Occurrence and activity of human intestinal bacteria involved in the conversion of dietary lignans.

  2006cited by this paper
• Intestinal Bacterial Communities That Produce Active Estrogen-Like Compounds Enterodiol and Enterolactone in Humans

  2005cited by this paper
• Dietary sesamin is converted to enterolactone in humans.

  2005cited by this paper
• Phytoestrogens and Their Human Metabolites Show Distinct Agonistic and Antagonistic Properties on Estrogen Receptor α (ERα)and ERβ in Human Cells

  2004cited by this paper
• Phytoestrogens and their human metabolites show distinct agonistic and antagonistic properties on estrogen receptor alpha (ERalpha) and ERbeta in human cells.

  2004cited by this paper
• Structure-activity relationship study of a diverse set of estrogen receptor ligands (I) using MultiCASE expert system.

  2003cited by this paper
• Transformation of arctiin to estrogenic and antiestrogenic substances by human intestinal bacteria.

  2003cited by this paper
• Bioavailability of phyto-oestrogens

  2003cited by this paper
• Biotransformation of pinoresinol diglucoside to mammalian lignans by human intestinal microflora, and isolation of Enterococcus faecalis strain PDG-1 responsible for the transformation of (+)-pinoresinol to (+)-lariciresinol.

  2003cited by this paper
• Structure-activity relationships for a large diverse set of natural, synthetic, and environmental estrogens.

  2001cited by this paper
• Human intestinal bacteria capable of transforming secoisolariciresinol diglucoside to mammalian lignans, enterodiol and enterolactone.

  2000cited by this paper
• Phyto-oestrogens: where are we now?

  1998cited by this paper
• Lignans from the roots of Urtica dioica and their metabolites bind to human sex hormone binding globulin (SHBG).

  1997cited by this paper
• Structural transformation of lignan compounds in rat gastrointestinal tract.

  1992cited by this paper
• Dietary phytoestrogens and cancer: in vitro and in vivo studies.

  1992cited by this paper

• Potential roles of gut microbes in biotransformation of natural products: An overview

  2022cites this paper
• Serial five-membered lactone ring ions in the treatment of Alzheimer’s diseases-comprehensive profiling of arctigenin metabolites and network analysis

  2022cites this paper
• Targeting Estrogen Signaling in the Radiation-induced Neurodegeneration: A Possible Role of Phytoestrogens

  2022cites this paper
• In Vivo and In Vitro Effects of Tracheloside on Colorectal Cancer Cell Proliferation and Metastasis

  2021cites this paper
• Arctigenin upregulates apoptosis through the AKT/MTOR pathway, inhibiting the proliferation of glioma

  2019cites this paper
• Human-relevant potency threshold (HRPT) for ERα agonism

  2018cites this paper
• Differential and directional estrogenic signaling pathways induced by enterolignans and their precursors

  2017cites this paper
• The anti-metastatic effects of the phytoestrogen arctigenin on human breast cancer cell lines regardless of the status of ER expression.

  2017cites this paper
• Biological effects induced by estrogenic activity of lignans

  2016cites this paper
• Estrogenic endocrine disruptors: Molecular mechanisms of action.

  2015cites this paper
• An 8-O-4' norlignan exerts oestrogen-like actions in osteoblastic cells via rapid nongenomic ER signaling pathway.

  2015cites this paper
• Effect of Natural Polyphenols on CYP Metabolism: Implications for Diseases.

  2015cites this paper
• Biological Evaluation of Anti-androgenic Effect of Some Plant Foods

  2014cites this paper
• Biotransformation on the flavonolignan constituents of Silybi Fructus by an intestinal bacterial strain Eubacterium limosum ZL-II.

  2014cites this paper
• Study on human intestinal bacterium Blautia sp. AUH-JLD56 for the conversion of arctigenin to (-)-3'-desmethylarctigenin.

  2013cites this paper