Integrated metabolomics, network pharmacology and molecular docking to characterize differences associated with geographical origin and subspecies on the antioxidant and α-glucosidase inhibition activity of sea buckthorn (Hippophae rhamnoides L.)

Introduction Sea buckthorn ( Hippophae rhamnoides L.) (SB) is a food-medicine homologous berry with well-recognized antioxidant and hypoglycemic potential. However, the influence of geographical origin and subspecies on its chemical composition and bioactivity remains incompletely understood. Methods In this study, untargeted metabolomics, network pharmacology, and molecular docking were integrated to characterize the metabolite profiles of SB berries harvested from Shanxi, Inner Mongolia, and Xinjiang, China, and to elucidate the mechanisms underlying their differential bioactivities. Results and discussion A total of 1,608 metabolites were annotated, and multivariate statistical analyses (PCA and OPLS-DA) revealed pronounced metabolic divergence among the three origins. The SB from Inner Mongolia (MG) exhibited the strongest activities in vitro antioxidant capacity (DPPH, ABTS, and FRAP assays) and α-glucosidase inhibitory capacity. This might be due to differences in subspecies and the dry and cold climate conditions in Inner Mongolia. Network pharmacology analysis found that the key proteins, including GAPDH, AKT1, TNF, IL-6, TP53 and EGFR, were might combined with core compounds of SB, such as 3,4-di-O-methylellagic acid. These findings preliminarily found how geographical origin and subspecies influenced the metabolite composition and bioactivity of SBs and provided a theoretical basis for the development of origin-specific functional foods.