An integrated analysis of metabolomics and transcriptomics offers profound insights into the mechanisms of metabolic differentiation between Semen Ziziphi Spinosae and Semen Jujubae

The seeds of Ziziphus jujuba var. spinosa, known as Semen Ziziphi Spinosae (wild jujube), serve as a significant medicinal and edible herb. In contrast, the seeds of Ziziphus jujuba var. jujuba, Semen Jujubae (cultivated jujube), are a by-product of fruit processing with underexplored potential. Although their functional differences are notable, the systematic metabolic distinctions and molecular regulatory mechanisms are not well understood. This study conducted a multi-omics comparative analysis under strictly controlled growth conditions. We analyzed the wild jujube seeds (Suanzao Ren, SR group) and the cultivated jujube seeds (Dazao Ren, DR group). Integrated analyses included morphological measurements, assessment of nutritional and bioactive components, antioxidant activity assays, and widely targeted metabolomics and transcriptomics. Phenotypic analysis demonstrated that DR had nutritional advantages in dry weight, total protein, and total soluble sugar content, whereas SR excelled in total flavonoids, total phenols, total saponins, and antioxidant activity. Metabolomics identified 933 differential metabolites, with flavonoids being the primary differential category. SR specifically accumulated flavonoid C-glycosides, while DR was enriched with anthocyanins. Transcriptome analysis revealed that differentiation stemmed from variations in the flavonoid metabolic pathway: the genes for flavonoid B-ring hydroxylase (F3’H/F3’5‘H) were upregulated in SR, inhibiting the downstream anthocyanin synthesis pathway; conversely, in DR, the complete anthocyanin synthesis module was activated. Weighted gene co-expression network analysis identified a gene module significantly associated with the accumulation of flavonoid C-glycosides in SR, including a module of 57 UDP-glycosyltransferase (UGT) genes, whose expression is highly correlated with the accumulation of flavonoid C-glycosides. The expression patterns of key genes in flavonoid synthesis were confirmed by quantitative real-time polymerase chain reaction (qPCR). This study revealed the metabolic and transcriptional basis of the functional differentiation between SR and DR. A putative core mechanism involves the reprogramming of flavonoid metabolic flux and the coordinated activation of the UGT gene module. This research provides essential metabolic markers and candidate gene targets for the precise differentiation and quality evaluation of SR and DR, and for the molecular breeding of SR varieties with enhanced medicinal value.