百合-车前草复合固体饮料抗高尿酸血症的体内作用机制研究

Therapeutic Mechanisms of a Lilium brownii-Plantago asiatica L.Compound Solid Beverage Against Hyperuricemia

摘要:

【目的】探讨百合-车前草复合固体饮料对高尿酸血症的缓解作用及其潜在机制。【方法】采用网络药理学筛选活性成分、作用靶点及相关通路，基于蛋白-蛋白相互作用（PPI）网络筛选关键靶蛋白并进行分子对接，最后通过动物试验验证百合-车前草复合固体饮料对血清尿酸水平、肾功能指标及尿酸生成相关酶活性和肾脏尿酸转运体水平的影响。【结果】网络药理学分析结果表明，百合和车前草中共有9种活性成分，与高尿酸血症的交集靶点共计61个，其中有13个靶点与高尿酸血症的治疗密切相关，主要涉及NF-κB、PI3K-Akt等信号通路。将蛋白-蛋白相互作用网络筛选得到的连接度排名前4的靶蛋白与9个活性成分进行分子对接，其对接能均小于-5.0 kJ/mol，表明对接良好，提示其具有降尿酸潜力。动物试验结果表明，与模型组相比，百合-车前草复合固体饮料干预后可使尿酸浓度下降30.46%，并能明显降低肌酐和尿素氮水平，同时还降低了小鼠肾脏黄嘌呤氧化酶（xanthine oxidase，XOD）和腺苷脱氨酶（adenosine deaminase，ADA）的酶活力，降低了肾脏尿酸转运体1（urate transporter 1，URAT1）水平，提高了肾脏有机阴离子转运体1（organic anion transporter 1，OAT1）和ATP结合转运蛋白G超家族成员2（ATP-binding cassette sub-family G member 2，ABCG2）水平。【结论】百合-车前草复合固体饮料可通过“多成分-多靶点-多通路”协同调控，降低尿酸水平并改善肾功能相关指标，该研究可为降尿酸功能饮料的研发提供理论依据。

Abstract:

[Objective] This study aims to investigate the ameliorative effects of a Lilium brownii-Plantago asiatica L. compound solid beverage on hyperuricemia and to elucidate its potential mechanisms.[Method] Network pharmacology was employed to screen the active constituents, potential targets, and related pathways. Key targets were identified based on a protein-protein interaction (PPI) network. Molecular docking was conducted between the key proteins and active constituents. An animal experiment was performed to validate the effects of the compound solid beverage on serum uric acid levels, renal function indices, activities of uric acid-producing enzymes, and the levels of renal urate transporters.[Result] Network pharmacology analysis indicated that Lilium brownii and Plantago asiatica L. contain a total of 9 active constituents and had 61 common targets with hyperuricemia, among which 13 targets were closely related to the treatment of hyperuricemia, mainly involving the NF-κB and PI3K-Akt signaling pathways. Molecular docking between the top 4 connectivity degree-ranked target proteins identified from the protein-protein interaction network and the 9 active constituents showed binding energy below -5.0 kJ/mol, indicating favorable interactions and suggesting uric acid-lowering potential. The animal experiment showed that compared with the model group, the Lilium brownii-Plantago asiatica L. compound solid beverage reduced the serum uric acid concentration by 30.46% and lowered serum creatinine and blood urea nitrogen levels (P<0.05). In addition, the beverage also decreased renal xanthine oxidase (XOD) and adenosine deaminase (ADA) enzyme activities, downregulated the urate transporter 1 (URAT1) level, and upregulated organic anion transporter 1 (OAT1) and ATP-binding cassette sub-family G member 2 (ABCG2) levels in the renal tissue.[Conclusion]The Lilium brownii-Plantago asiatica L. compound solid beverage may lower uric acid levels and improve renal function-related indices through a multi-constituent, multi-target, and multi-pathway synergistic mechanism. The findings provide a theoretical basis for the development of uric acid-lowering functional beverages.