Plant Metabolome Between Root and Aerial Parts of Cichorium intybus L. and Anti-Hyperuricemia Mechanisms Based on Cell Metabolomics

<b>Background/Objectives</b>: Hyperuricemia (HUA) is a metabolic disease with increasing incidence. Chicory (<i>Cichorium intybus</i> L.), a traditional medicinal and edible plant, has demonstrated anti-HUA effects. However, the metabolic profiles of its aerial parts and roots are still not fully characterized. Moreover, few studies have investigated its anti-HUA effects using cell metabolomics. <b>Methods</b>: The metabolomes of chicory root and aerial parts were characterized using UPLC-QTOF-MS-based untargeted metabolomics. Subsequently, the anti-HUA mechanism of chicory root was investigated by performing non-targeted metabolomics in HK-2 cells. <b>Results</b>: The results demonstrated that various hydroxycinnamic acids and flavonoids were more abundant in aerial parts, whereas sesquiterpenes and oligosaccharides were characteristic of the root. Both chicory root and aerial part extracts significantly reduced uric acid (UA) levels in HK-2 cells induced by adenosine with xanthine oxidase (XO). Cellular metabolomic profiling indicated a distinct separation between the root extract (CR40, 40 mg/mL) and the model group. OPLS-DA identified 165 differential metabolites, including acylcarnitines, acylamino acids, peptides, phospholipids, glycerides, and lipid-like molecules. These metabolites were associated with key metabolic pathways of sphingolipids, glycerophospholipids, phosphonate and phosphinate, linoleic acid, biotin, purine, as well as taurine and hypotaurine metabolism. <b>Conclusions</b>: Chicory is rich in diverse bioactive compounds and exhibits significant anti-HUA activity by modulating multiple metabolic pathways.