Angelica biserrata (Shan et Yuan) Yuan et Shan ( A. biserrata ) roots polysaccharides (ABP) are important bioactive constituents with considerable antioxidant potential. However, the ecological regulation of their activity variation and the underlying structure–activity relationships remain poorly understood. In this study, MaxEnt modeling combined with field surveys was used to identify highly suitable habitats for A. biserrata and representative sampling sites for four ecotypes. ABP from these ecotypes were comparatively characterized by physicochemical and structural analyses, in vitro antioxidant assays, an H₂O₂ induced oxidative injury model in MRC 5 cells, transcriptomic profiling, and machine learning based association analysis. The results revealed that, among the four ecotypes, the Hubei Enshi (HE) sample had the highest polysaccharide, glucose (Glc), and galacturonic acid (Gal-UA) contents and the lowest molecular weight. It also exhibited the strongest scavenging activities against hydroxyl, ABTS⁺, and DPPH radicals, with IC₅₀ values of 0.52, 0.49, and 0.88 mg/mL, respectively, as well as the greatest protective effect in H₂O₂ injured MRC-5 cells (EC₅₀ = 0.27 mg/mL). Random forest and correlation analyses identified annual precipitation (Bio12), precipitation of the warmest quarter (Bio18), minimum temperature of the coldest month (Bio6), and solar radiation in May (Srad5) as the major environmental drivers. GlC, Gal-UA, and Mw were key structural determinants of ABP antioxidant activity. Integrated transcriptomic analysis identified PFKA3 , AAPC1 , and PGKY as potential key genes influencing the structural characteristics of ABP. This study provides a theoretical basis for the ecological cultivation of high quality A. biserrata and the efficient utilization of ABP resources. • Integrated environment, structure, genes, and bioactivity decoded ecotype variation. • Bio12, Bio18, etc. were key drivers of gene expression and polysaccharide structure. • PFKA3 and AAPC1 may be key upstream responsive nodes for ecotype divergence. • Antioxidant activity was co-regulated by Glc, Gal-UA, and molecular weight.
HU et al. (Wed,) studied this question.