Lignans: current trends in production through plant tissue culture, biological activities, and formulation methods

Lignans constitute an important class of plant secondary metabolites, widely distributed throughout the plant kingdom and biosynthesized via the oxidative coupling of phenylpropane units. These phenolic compounds have become key components of translational medicine and the nutraceutical industry, thanks to their wide range of biological activities. These activities include antitumor, antioxidant, anti-inflammatory, antiviral, neuroprotective, cardioprotective, and hormone-modulating effects, making them strategic candidates for treating chronic degenerative diseases with high global prevalence. However, harnessing their therapeutic potential presents significant challenges, as their taxonomic distribution is limited and their concentrations are concentrated in a few plant families, thereby hindering their commercial availability. Furthermore, the stereochemical complexity of their structures, characterized by multiple chiral centers, imposes significant barriers to total chemical synthesis and reduces the economic viability of synthetic routes. This gap between growing demand and limited natural supply underscores the urgent need to explore new plant species that produce lignans. In this context, this review critically examines the main sources of lignans, including direct extraction from plant biomass, chemical synthesis, and biotechnological production through callus cultures, cell suspensions, and hairy root cultures. The bioactivities and molecular mechanisms of lignans and neolignans obtained by biotechnological methods are further explored, including analyses of species distribution and molecular targets. Finally, the review discusses the advantages and limitations of different production platforms, challenges associated with industrial-scale production, and future perspectives for the sustainable and scalable development of lignan-based products.