Supplements extracted from <i>Lophatherum gracile</i> Brongn. ameliorates hyperuricemia by regulating nucleotide metabolic enzymes and urate transporters

Hyperuricemia (HUA) has gradually become the fourth most prevalent chronic disease and the incidence rate is getting younger. In this study, <i>Lophatherum</i> <i>gracile</i> Brongn. with uric acid (UA)-lowering effects were screened from medicine food homology (MFH) plants by UA overproduction and excessive absorption cell models. Further, a murine model of potassium oxonate and yeast-induced HUA was used to evaluate the <i>in vivo</i> anti-high UA and nephroprotective effects of <i>L. gracile,</i> which significantly reduced serum UA and increased urine UA levels in HUA mice. <i>L. gracile</i> effectively inhibits the overproduction of UA by decreasing the activities of xanthine oxidase and adenosine deaminase (ADA), promoting excrement by regulating the mRNA expression of glucose transporter 9<i>.</i> Moreover, active components of <i>L. gracile</i> were analyzed by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry/mass spectrometry (HPLC-QTOF-MS/MS), network pharmacology was used to identify active ingredients further and validate targets. The results of network pharmacology showed that the components of the <i>L. gracile</i> acted on the targets xanthine dehydrogenase (XDH), adenosine deaminase (ADA), solute carrier family 2 member 9 (SLC2A9), and so on, which was consistent with the previous verification. The most likely active substances of <i>L. gracile</i> hydrojuglone glucoside. The effect of reducing UA is discovered for the first time in <i>L. gracile</i>. These findings suggested that <i>L. gracile</i> could be used as a potential confrontational strategy for the development of anti-HUA functional foods, providing the theoretical basis for the application of MFH plants and the development of related functional food products.