An altered tissue distribution of flaxseed lignans and their metabolites in Abcg2 knockout mice

Abstract

Lignans are dietary polyphenols, which are metabolized by gut microbiota into the phytoestrogenic metabolites enterolignans, mainly enterolactone and enterodiol. Breast Cancer Resistance Protein (BCRP/ABCG2) is an efflux transporter that affects the plasma and milk secretion of several drugs and natural compounds. We hypothesized here that Abcg2 could influence the levels of lignans and their derived metabolites in target tissues. Consequently, we aimed to evaluate the role of Abcg2 in the tissue distribution of these compounds. We used Abcg2 knockout and wild-type male mice fed with a lignan-enriched diet for one week and analysed their plasma, small intestine, colon, liver, kidneys and testicles. High levels of lignans as well as enterolignans and their glucuronide and sulfate conjugates in the small intestine and colon were detected, with higher concentrations of the conjugates in the wild-type compared with Abcg2 mice. Particularly relevant was the detection of 24-fold and 8-fold higher concentrations of enterolactone-sulfate and enterolactone-glucuronide, respectively, in the kidney of Abcg2 compared with wild-type mice. In conclusion, our study showed that lignans and their derived metabolites were in vivo substrates of Abcg2, which affected their plasma and tissue levels. These results highlight the role of Abcg2 in influencing the health-beneficial properties of dietary lignans.

In silico and in vitro identification of secoisolariciresinol as a re-sensitizer of P-glycoprotein-dependent doxorubicin-resistance NCI/ADR-RES cancer cells

“…It is, thus, logical that both transporters might share the same inhibitors of DOX transport. A lignan derived from flaxseed, namely secoisolariciresinol (SECO), was reported as an inhibitor of BCRP (García-Mateos et al, 2018). The aim of the current study was to prove, using in silico MD studies, that SECO interacts with P-gp by comparing it to verapamil, as well as to confirm this interaction by in vitro studies using cancer cells.…”

Secoisolariciresinol Diglucoside of Flaxseed and Its Metabolites: Biosynthesis and Potential for Nutraceuticals

“…SDG might have the potential to promote early enhancement of mammary gland differentiation, which could protect against breast cancer (Tan et al, 2004; Adolphe et al, 2010). However, García-Mateos et al (2018) showed that the preventive potential of SDG and its metabolites could be affected by the breast cancer resistance protein (BCRP/ABCG2) (García-Mateos et al, 2018).…”

Serumal Lipidomics Reveals the Anti-inflammatory Effect of Flax Lignans and Sinapic Acid in High-Fat-Diet-Fed Mice

“…5−7 These compounds effectively bind to glucuronic acid or to a lesser extent bind to sulfate radicals in the intestinal epithelium and liver and pass through the enterohepatic circulation. 7 Several studies have focused on the beneficial effects of SDG or SA, especially on antioxidation 6,8,9 and antiinflammation function. 10−12 However, the inflammationalleviating effect of SDG or SA in obesity, hyperglycemia, hypertension, and even cardiovascular disease in these studies was usually validated via biochemical measurements, gene expression analysis, and clinical assessments.…”

“…In nature, one of the richest dietary sources of lignans is flaxseed (Linum usitatissimum), in which the lignan production is 800 times higher than that of other oil seeds, cereals, legumes, fruits, and vegetables . The principal dietary lignan present in flaxseed is secoisolariciresinol diglucoside (SDG), which is metabolized by the intestinal microbiota via secoisolariciresinol (SECO) into the phytoestrogenic enterolignans enterodiol (END) and enterolactone (ENL). − These compounds effectively bind to glucuronic acid or to a lesser extent bind to sulfate radicals in the intestinal epithelium and liver and pass through the enterohepatic circulation . Several studies have focused on the beneficial effects of SDG or SA, especially on antioxidation ,, and anti-inflammation function. − However, the inflammation-alleviating effect of SDG or SA in obesity, hyperglycemia, hypertension, and even cardiovascular disease in these studies was usually validated via biochemical measurements, gene expression analysis, and clinical assessments.…”