The combined transcriptome and metabolome analysis reveals the regulatory mechanisms and temporal differences of exogenous selenium in promoting flavonoids and glycyrrhizic acid metabolism in licorice under cadmium stress

Glycyrrhiza uralensis Fisch. is a valuable medicinal plant whose roots contain glycyrrhizic acid and flavonoids as key bioactive compounds. However, soils in major licorice-producing areas are increasingly threatened by cadmium (Cd) contamination, which adversely affects both plant yield and the accumulation of medicinal components. Although selenium (Se) can reduce Cd uptake, its regulatory effects on glycyrrhizic acid and flavonoids biosynthesis under Cd stress remain unclear. This study established three treatment groups (Cd0_Se0, Cd20_Se0, and Cd20_Se1) across two time points (12 h and 30 d) and integrated multi-omics analyses to elucidate how exogenous Se modulates the metabolism of flavonoids and glycyrrhizic acid in G. uralensis under Cd stress. Compared with Cd20_Se0, Cd20_Se1 increased biomass (shoots: +46.56%; roots: +41.57%) and alleviated oxidative stress. Se restored glycyrrhizic acid biosynthesis by regulating the MVA and MEP pathways and UGT genes, enhancing accumulation at 30 d. For flavonoids, Se upregulated key genes ( F3H , CHI , CHS , and ANR ) at 12 h, promoting EGCG and baicalin. At 30 d, a gene network ( PAL , 4CL , CHS , and ANR ) strengthened phenylpropanoid metabolism and increased liquiritin and baicalin levels. Collectively, these findings demonstrate that Se effectively alleviates Cd-induced stress, with long-term application exerting particularly pronounced benefits, sustainably mitigating the inhibition of glycyrrhizic acid biosynthesis, and temporally regulating key genes to maintain flavonoids homeostasis. This study provides valuable insights into Cd contamination control and quality enhancement in licorice cultivation and offers novel molecular-level evidence for Se-mediated biofortification in medicinal plants. • Selenium treatment alleviated cadmium-induced growth inhibition in licorice. • Selenium promoted glycyrrhizic acid and flavonoids synthesis, improving licorice quality. • Selenium boosted glycyrrhizic acid through MVA/MEP/ UGTs , while restoring flavonoids via gene regulation under Cd stress. • Long-term selenium addition alleviated cadmium toxicity in cadmium-treated licorice. • This co-application strategy enhanced both the quality and yield of licorice plants.