Biostimulants reprogram alkaloid biosynthesis through hormonal crosstalk and transcriptional regulation

Alkaloids derived from plants are among the most significant classes of specialized metabolites due to their wide range of applications in pharmaceutical, nutraceutical and industrial sectors. However, the natural accumulation of these compounds is often limited by environmental factors, metabolic bottlenecks, and the inherent trade-off between plant growth and secondary metabolism. Recently, biostimulants have emerged as a sustainable tool to improve alkaloid production because they reprogram plant metabolic networks rather than acting only as nutrient supplements. The review critically synthesizes current knowledge on molecular mechanisms involved in the modulation of alkaloid biosynthesis in medicinal plants by major classes of biostimulants, including seaweed extracts, humic and fulvic substances, microbial biostimulants and protein hydrolysates. Special emphasis is given to the role of specific bioactive components, such as laminarin, fucoidan, alginates, humic fractions, signaling peptides, siderophores, and phytohormones-like compounds, in triggering jasmonic acid-, salicylic acid-, and MAPK-mediated signaling pathways that modulate the expression of key biosynthetic enzymes and transcription factors involved in the regulation of specialized metabolism. Furthermore, the review covers carbon-nitrogen partitioning, growth-defense optimization, timing of application, delivery methods, and interactions with abiotic stresses, all of which influence biostimulant efficacy. Current limitations such as formulation variability, inadequate mechanistic insight, poor multi-omics integration and limited field validation are critically discussed. Finally, future perspectives include the integration of transcriptomics, proteomics, metabolomics, genome editing, synthetic biology, artificial intelligence-assisted metabolic modeling and precision agriculture for the identification of regulatory hubs and development of next generation component biostimulants. These advances are expected to enable predictable, sustainable and commercially scalable production of high-value alkaloids and to improve medicinal plant resilience to changing environmental conditions. Graphical abstract