Black Rice Anthocyanin–Hyaluronic Acid Complex Alleviates Hyperuricemia-Associated Renal Injury Through Synergistic Inhibition of the TLR4/NF-κB Pathway and Modulation of Uric Acid Transport

Abstract

Hyperuricemia-associated renal injury is closely linked to oxidative stress and inflammation, highlighting the need for safe dietary intervention. This study evaluated the protective effects of a black rice anthocyanin (ATC)–hyaluronic acid complex (HAA) against uric acid (UA)-induced injury. In UA-induced human renal proximal tubular epithelial (HK-2) cells, black rice ATCs, HA, and HAA improved cell viability and antioxidant defenses, as shown by increased glutathione (GSH) levels and catalase (CAT) and superoxide dismutase (SOD) activities. They also reduced malondialdehyde (MDA), reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). HAA produced a greater reduction in TLR4/NF-κB-related inflammatory gene expression, suggesting that its cytoprotective and anti-inflammatory effects may be associated with modulation of this inflammatory axis. In hyperuricemic mice, HAA lowered serum UA, creatinine, and blood urea nitrogen levels, inhibited hepatic xanthine oxidase and adenosine deaminase activities, and attenuated renal histopathological injury. HAA also reduced the mRNA expression of urate reabsorption-related genes, including GLUT9, OAT4, and OAT10, while increasing that of urate excretion-related genes, including OAT1 and ABCG2, which may contribute to improved urate homeostasis. These findings support the potential of HAA as a functional dietary ingredient for the management of hyperuricemia-associated metabolic disturbances and renal injury.