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Objective: Hyperuricemia (HUA) is a metabolic disorder characterized by abnormally elevated serum uric-acid levels. This study investigated the inhibitory effect of a chrysanthemum compound formula (CCF) on xanthine oxidase (XOD) in vitro and further elucidated its urate-lowering mechanisms. Methods: The in vitro XOD inhibitory activity of CCF was first validated. Network pharmacology was then employed to identify key therapeutic targets, active ingredients, and signaling pathways involved in CCF-mediated treatment of HUA. Key active constituents were subjected to molecular docking with XOD. In animal experiments, a HUA mouse model was established, and mice were orally administered CCF at three doses (100, 150, and 200 mg/kg). Serum uric acid (UA) and liver XOD activity were measured, along with blood urea nitrogen (BUN) and creatinine (CRE). Renal levels of TNF-α and IL-1β were quantified by ELISA, and histopathological examination of kidney tissue was performed. Western blotting was used to analyze urate transporters and relevant signaling pathways. Results: CCF dose-dependently inhibited XOD activity in vitro. Network pharmacology indicated that CCF might exert therapeutic effects against HUA via the NF-κB signaling pathway. Quercetin, kaempferol, luteolin, β-sitosterol, and isorhamnetin were identified as the principal bioactive constituents; molecular docking confirmed their stable binding to XOD. In vivo, CCF significantly reduced serum UA levels in HUA mice (P<0.001) and alleviated renal inflammation. Western blot results showed down-regulation of the urate re-absorption transporters URAT1 and GLUT9, and up-regulation of the urate excretion transporters OAT1 and ABCG2 (P<0.001 or P<0.05), thereby promoting uric-acid excretion. In treated mice, IκBα expression increased, whereas the p-p65/p65 ratio decreased. Conclusion: CCF effectively reduces serum uric-acid levels and alleviates kidney damage, likely by modulating the NF-κB signaling pathway.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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