Revealing the key antioxidant compounds and potential action mechanisms of Pinus koraiensis pinecones by integrating UPLC-MS- based widely targeted metabolomics, network pharmacology, and molecular docking approaches

Pinus koraiensis represents a vital forest resource with significant economic and ecological value in the forestry and timber industries. Pinus koraiensis pinecone (PKP) is a promising yet underutilized natural antioxidant source with considerable potential. However, due to the limited characterization of its phytochemical composition, PKP is predominantly discarded as firewood, leading to substantial resource wastage. This study comprehensively assessed the antioxidant activity and metabolite profile of PKP from three provenances—Lushuihe (LSH), Dongfanghong (DFH), and Dailing (DL)—using chemical antioxidant assays and widely targeted metabolomics. Additionally, key antioxidant constituents and their underlying mechanisms were elucidated through network pharmacology and molecular docking analyses. The findings indicated that the antioxidant capacity followed the order LSH > DFH > DL. A total of 2,889 metabolites were identified via UPLC-ESI-Q TRAP-MS/MS, predominantly comprising flavonoids (21.4%), terpenoids (14.15%), and phenolic acids (10.18%). Multivariate statistical analysis pinpointed 18 key antioxidant compounds. Network pharmacology revealed their involvement in multiple metabolic pathways, including PI3K/AKT, AGE-RAGE and EGFR signaling pathways. Molecular docking demonstrated that these bioactive compounds interact with core antioxidant targets via hydrogen bonding, hydrophobic interactions, salt bridges, and π-cation interactions. Among them, kaempferol-3- O -(4''- O -p-coumaroyl)rhamnoside, isolugrandoside, rubiprasin A, and deoxyerythrolaccin exhibited strong binding affinity (binding energy ≤ -9.0 kcal/mol) with SRC, CTNNB1, CASP3, and TNF. These findings underscore the potential of PKP as a sustainable industrial antioxidant source with promising applications in nutraceutical and pharmaceutical sectors.