Figure 4.

Flaxseed lignan absorption, first-pass metabolism, and enterohepatic recycling. The flaxseed lignan, secoisolariciresinol diglucoside (SDG), is biotransformed by bacteria in the gastrointestinal tract upon oral intake. Due to their lipophilicity, the aglycones and mammalian lignans may cross biological membranes via passive diffusion. With permeation into the enterocyte a portion of the aglycone and mammalian lignans undergo first-pass metabolism by phase II enzymes (e.g., UDP-glucuronosyltransferases (UGT), sulfotransferases (ST)). The polar, water-soluble glucuronide and sulfate conjugates require transport across the basolateral membrane of the intestinal epithelium by active transporters to gain access to the portal blood supply. Unmetabolized aglycone and mammalian lignans enter the hepatocyte by passive diffusion and undergo phase II metabolism by UGTs and STs. The conjugated metabolites are actively transported into the bile and can be reintroduced into the gastrointestinal tract. Here, they can be deconjugated and undergo reabsorption, a process called enterohepatic recirculation (EHR). The various lignans and their corresponding metabolites may elicit biological responses upon entering the systemic circulation by interacting with various enzymes, transporters, and other cell signaling macromolecules. Elimination of the conjugated metabolites can occur through either fecal or renal excretion. Adopted from reference [403].