Enterodiol

International Journal of Angiology, 2000, 9(04):220-225.

Antioxidant activity of secoisolariciresinol diglucoside-derived metabolites, secoisolariciresinol, Enterodiol, and enterolactone.[Reference: WebLink]

METHODS AND RESULTS:
Secoisolariciresinol diglucoside (SDG), an antioxidant isolated from flaxseed, is metabolized to secoisolariciresinol (SECO), Enterodiol (ED), and enterolactone (EL) in the body. The effectiveness of SDG in hypercholesterolemic atherosclerosis, diabetes, and endotoxic shock could be due to these metabolites. These metabolites may have antioxidant activity. However, the antioxidant activity of these metabolites is not known. The antioxidant activity of SECO, ED, and EL was investigated using chemiluminescence (CL) of zymosan-activated polymorphonuclear leukocytes (PMNLs) [PMNL-CL]. Other antioxidants (SDG and vitamin E) were also used for comparison. SDG, SECO, ED, EL, and vitamin E, each in the concentration of 0.5, 1.0, 2.5, 5.0 and 10.0 mg/ml, produced a concentration-dependent reduction in zymosan-activated PMNL-CL. SDG, SECO, ED, EL, and vitamin E, in the concentration of 2.5 mg/ml, produced a reduction of zymosan-activated PMNL-CL by 23.8%, 91.2%, 94.2%, 81.6% and 18.7%, respectively. Activated PMNLs produce reactive oxygen species and luminol-dependent CL reflects the amount of oxygen species generated from activated PMNLs. The reduction of PMNL-CL, therefore, reflects the antioxidant activity of the compounds studied.
CONCLUSIONS:
These results suggest that the metabolites of SDG have antioxidant activity. The antioxidant activity was highest with SECO and ED and lowest with vitamin E. The antioxidant potency of SECO, ED, EL, and SDG was 4.86, 5.02, 4.35, and 1.27 respectively, as compared to vitamin E. SECO, ED and EL are respectively 3.82, 3.95, and 3.43 more potent than SDG.

Journal of the Science of Food & Agriculture,2019,99(4):2411-2419.

Apoptotic effect of enterodiol, the final metabolite of edible lignans, in colorectal cancer cells.[Reference: WebLink]

Enterodiol (END) is transformed by human intestinal bacteria from lignans contained in various whole‐grain cereals, nuts, legumes, flaxseed, and vegetables. It is known to have several physiological effects, but its effects on mitogen‐activated protein kinase (MAPK) signaling and apoptosis in colorectal cancer (CRC) cells have not yet been elucidated.
METHODS AND RESULTS:
We therefore investigated the effects of END on apoptosis in CRC cells and whether these effects are mediated via MAPK signaling. Cell proliferation was decreased by END treatment in a time‐dependent manner. In particular, END treatment resulted in an apoptosis rate of up to 40% in CT26 cells but showed no cytotoxicity toward RAW264.7 macrophages. Treatment with END also suppressed the migration of CRC cells in a concentration‐dependent manner. The phosphorylation of extracellular signal‐regulated kinase (ERK), jun N‐terminal kinase (JNK), and p38 was down‐regulated with END treatment. Furthermore, END decreased the expression levels of anti‐apoptotic proteins in CRC cells. Enterodiol inhibited the growth of CRC cells by controlling the MAPK signaling pathway involved in proliferation and apoptosis.
CONCLUSIONS:
These results demonstrate that END has an apoptotic effect in CRC cells.

Journal of steroid biochemistry & molecular biology, 2008, 110(1-2):0-185.

Enterodiol and enterolactone, two major diet-derived polyphenol metabolites have different impact on ERα transcriptional activation in human breast cancer cells.[Reference: WebLink]

Lignans are plant compounds metabolized in the mammalian gut to produce the estrogenic enterolignans, Enterodiol (ED) and enterolactone (EL). Because estrogens have been linked to breast cancer etiology, enterolignans could affect breast cancer risk, but to our knowledge, the mechanisms by which they exert their estrogenic and/or anti-estrogenic effects in humans are still unclear.
METHODS AND RESULTS:
To better understand how estrogenic compounds from the food, such as the enterolignans, might influence breast cancer progression and their mechanisms to interfere with human estrogen receptor (ER) signalling in hormone-dependant diseases, we examined and compared the ability of ED, EL and 17β-estradiol (E2) to induce the transactivation of ERα and ERβ, to modulate ERα target genes, to exert either growth stimulatory or anti-proliferative effects and finally to modulate MCF-7 cell migration by acting on matrix metalloproteases (MMP)-2 and -9, at concentrations that are achievable through a lignan-rich diet. This study indicates that enterolignans show distinct properties for transactivation of ERα and ERβ. ED, as E2, induces ERα transcriptional activation through transactivation functions AF-1 and AF-2, while EL is less efficient in inducing AF-1, acting predominantly through AF-2. Furthermore, ED and EL modulate ERα mRNA and protein contents as well as MCF-7 cell proliferation and secreted MMP activities in a different way.
CONCLUSIONS:
Enterolignans are compounds of wide interest nowadays and our results help to unveil their mechanisms of action on ER, emphasizing the fact that the dietary load in lignans could be of importance in the balance between being risk or chemopreventive factors for breast cancer and women's health.

Journal of Agricultural & Food Chemistry, 2010, 58(11):6678-6684.

Enterodiol and enterolactone modulate the immune response by acting on nuclear factor-kappaB (NF-kappaB) signaling.[Reference: WebLink]

Lignan-rich whole-grain cereals, beans, berries, and nuts show protective effects against a variety of chronic diseases, including cancer.
METHODS AND RESULTS:
Lignans are converted by intestinal microflora to enterolactone (EL) and its oxidation product Enterodiol (ED). To investigate the immunomodulatory effect of EL and ED in human cells, peripheral blood lymphocytes were treated with increasing physiologically relevant concentrations of EL and ED (0-1000 microM) and stimulated with lipopolysaccharide (LPS) and anti-CD3 plus anti-CD28 monoclonal antibodies. A dose-related inhibition of cell proliferation and cytokine production was observed, with EL being the most active.
CONCLUSIONS:
Molecular investigations in THP-1 cells showed that both EL and ED prevented inhibitory-kappaB (I-kappaB) degradation and nuclear factor-kappaB (NF-kappaB) activation, which in turn resulted in decreased tumor necrosis factor-alpha (TNF-alpha) production. EL and ED were also able to pass the intestinal barrier and modulate cytokine production. The findings of the present study reveal potential mechanisms that could explain some in vivo beneficial effects of lignans.