biostudies-literatureWang HKunming Institute of Botany, Chinese Academy of SciencesNational Natural Science Foundation of China103637https://www.ebi.ac.uk/biostudies/studies/S-EPMC12907897biostudies-literatureUnknown34Coffee "husks", as primary by-products whose inadequate disposal causes environmental pollution, are rich in bioactive ingredients. The in-depth exploration and practical application of these by-products remain insufficient. A comprehensive investigation was performed with the combination of LC-MSⁿ-IT-TOF analysis, antioxidant and xanthine oxidase (XO) inhibitory assays. A total of 55 main characteristic compounds were identified and their detailed mass spectrometry cleavage patterns were elucidated. Chlorogenic acid analogs as key bioactive constituents comprised over 66% of the identified phenols, which spontaneously bind to XO, with binding energy ranging from -4.46 to -3.32 kcal/mol. The antioxidant activities of di-substituted chlorogenic acids were significantly higher than those of mono-substituted molecules. Flavonoids from the "husks" with XO inhibitory activities were attributed to the flavone skeleton, in which the presence of a stable chromone group was vital. These results provided novel perspectives for discovery of XO inhibitors from widely discarded natural by-products like coffee "husks".Food chemistry: XMain characteristic metabolites with xanthine oxidase inhibitory activities from Yunnan <i>Coffea arabica</i> husks.PMC1290789732160536Li YLiang WWan LZhao WWang HWang YfalseMain characteristic metabolites with xanthine oxidase inhibitory activities from Yunnan <i>Coffea arabica</i> husks.Coffee "husks", as primary by-products whose inadequate disposal causes environmental pollution, are rich in bioactive ingredients. The in-depth exploration and practical application of these by-products remain insufficient. A comprehensive investigation was performed with the combination of LC-MSⁿ-IT-TOF analysis, antioxidant and xanthine oxidase (XO) inhibitory assays. A total of 55 main characteristic compounds were identified and their detailed mass spectrometry cleavage patterns were elucidated. Chlorogenic acid analogs as key bioactive constituents comprised over 66% of the identified phenols, which spontaneously bind to XO, with binding energy ranging from -4.46 to -3.32 kcal/mol. The antioxidant activities of di-substituted chlorogenic acids were significantly higher than those of mono-substituted molecules. Flavonoids from the "husks" with XO inhibitory activities were attributed to the flavone skeleton, in which the presence of a stable chromone group was vital. These results provided novel perspectives for discovery of XO inhibitors from widely discarded natural by-products like coffee "husks".2026-01-01T00:00:00Z2026 Feb2026-07-16T05:11:59.206Z2026-07-09T10:36:49.213ZS-EPMC129078974170487410.1016/j.fochx.2026.103637