Urate-lowering and renal-protective effects of sugarcane polyphenols in hyperuricemia: mechanisms and key components

Hyperuricemia (HUA) is a metabolic disorder characterized by abnormally elevated levels of uric acid (UA) in the blood, often accompanied by renal damage. The continuous rise in HUA incidence necessitates the development of safe, efficient natural urate-lowering pathways. This study combined network pharmacology prediction with rat model experiments to systematically evaluate the urate-lowering potential of sugarcane polyphenols (SP), a byproduct of the sugarcane sugar industry. The results showed that the intake of low, medium, and high doses of SP significantly reduced the serum UA levels in HUA rats to 19.77%, 27.42%, and 45.54%, respectively. Moreover, SP significantly improved liver and kidney function damage, as evidenced by reduced levels of blood urea nitrogen (BUN), creatinine (CRE), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Mechanistic studies revealed that SP regulates UA metabolism through two distinct mechanisms: reducing production and promoting excretion. Specifically, SP inhibited hepatic xanthine oxidase (XOR) activity, thereby reducing UA synthesis. Concurrently, SP enhanced UA excretion by upregulating the expression of ATP-binding cassette subfamily G member 2(ABCG2) and downregulating the expression of urate transporter 1(URAT1) and glucose transporter 9(GLUT9). When the total phenolic content was equivalent to SP, the chlorogenic acid (CGA) group showed urate-lowering activity similar to that of SP. This suggests that CGA may play an essential role in the ability of SP to reduce UA. Additionally, SP inhibited inflammation-related molecule expression and improved histopathological changes in the kidneys of HUA rats by affecting the PI3K/AKT/NF-κB signaling pathway, further substantiating the renal protective effects of SP in HUA conditions. The results of this study provide a theoretical basis for the in vivo urate-lowering activity of SP rich in CGA and its alleviation of renal damage. This may offer theoretical references for the comprehensive utilization of SP, a byproduct of the sugarcane sugar industry, laying the foundation for the high-value utilization of sugarcane byproducts and the development of polyphenol functional activity products.