Geographical origin orchestrates acteoside accumulation in Rehmannia glutinosa via coordinated transcriptomic and metabolomic reprogramming

Introduction The geo-authenticity of medicinal plants, exemplified by Rehmannia glutinosa , is largely attributed to environmentally driven variation in bioactive compounds; yet, the underlying systemic molecular mechanisms remain elusive. Methods This study employed an integrated approach combining targeted quantitative analysis, transcriptomics, and metabolomics to dissect how geographical origin shapes the medicinal quality of Rehmannia glutinosa , using two cultivars ('Wen 85-5' and 'Jin Jiu') sourced from two distinct production regions (Henan and Hebei). Results Targeted quantification confirmed origin-specific accumulation patterns of key bioactive compounds, most notably a significantly higher acteoside content in roots from the Henan origin. Multi-omics profiling revealed a conserved core molecular response to geographical origin, involving 894 common differentially expressed genes and 443 common differentially abundant metabolites enriched in hormone signaling, primary metabolism, and specialized biosynthesis pathways. While the response amplitude was genotype-dependent (stronger in 'Wen 85-5'), its fundamental architecture was consistent. Crucially, we identified a coordinated upregulation of the entire acteoside biosynthetic network in Henan-sourced roots. This was evidenced by the concerted induction of key structural genes ( PAL, C4H, 4CL, TyDC, UGT ) across both phenylpropanoid and tyrosine-derived branches, coupled with elevated levels of pathway intermediates. Conclusion This study elucidates that the geo-authenticity of Rehmannia glutinosa arises from an origin-triggered, systemic reconfiguration of interconnected transcriptional and metabolic networks. The identified core regulatory network provides a mechanistic framework for understanding quality formation and paves the way for molecular-assisted cultivation and breeding strategies.