Biological effects induced by estrogenic activity of lignans

•The biological effects induced by estrogenic activity of lignans are summarized.•Structural characteristics of estrogenic lignans, and their signaling pathways and cell functions are summarized.•The importance of mechanism-based understanding of estrogenic lignans is discussed.

BackgroundLignans are an important category of phytoestrogens and contribute to human health as food, supplements and medicines. Estrogenic lignans are classified by their various biological effects as revealed by assays used to evaluate estrogenicity, and cell signaling pathways and functions that are often associated with other signaling pathways and signal mediators. Although some assays give consistent results, others have shown contradictory results.Scope and approachThe biological effects induced by estrogenic activity of lignans are summarized here by a comprehensive search of literature associated with their signaling pathways and cell functions.Key findings and conclusionsEstrogenic lignans have structural characteristics, such as those mimicking the presence of and the distance between the hydroxyl groups at position 3 of the steroid A-ring and position 17 of the D-ring, and aromatic hydrophobicity. The signaling pathways induced by lignans include specific pathways, such as the estrogen receptor (ER) and mitogen-activated protein kinase (MAPK) pathways, and specific cell functions such as chromatin/epigenetic regulation, apoptosis, autophagy, cellular metabolism, translational control, cell cycle/DNA damage control, cytoskeletal/adhesion regulation, immunological/inflammatory response, neurodegenerative diseases and development/differentiation. In addition, crosstalk of receptor signaling was observed between estrogen signaling and other signaling pathways. Due partly to the fact that lignans do not cause adverse reactions or increase health risks, applications of estrogenic lignans in food, supplements, diagnostics, therapeutics and medicines have been explored. To further explore the applications of estrogenic lignans, it is essential to understand their mechanism of action, especially at the cell signaling level.