Modulation of NLRP3 inflammasome and uric acid metabolism by small molecule pectin from Premna ligustroides Hemsl leaves: Implications for hyperuricemia management.

Abstract

The NOD-like receptor protein 3 (NLRP3) inflammasome represents a promising target for drug therapies and dietary interventions aimed at reducing uric acid secretion. This study explored the effects of enzymatically hydrolyzed small-molecule pectin derived from Premna ligustroides Hemsl leaves (SMP) on the NLRP3 inflammasome and PDZ domain-containing 1 (PDZK1)/urate transporters. The findings demonstrated that SMP significantly lowered serum levels of uric acid, creatinine, urea nitrogen, xanthine oxidase, adenosine deaminase, and liver interleukins (IL)-1β, IL-18, IL-6, and tumor necrosis factor-α (TNF-α) compared to the hyperuricemic model group. In the renal medulla and cortex, SMP upregulated the expression of uric acid secretion proteins, including organic anion transporter 1 (OAT1), type 1 sodium-dependent phosphate transporter (NPT1), NPT4, and ATP-binding cassette subfamily G member 2 (ABCG2), as well as the transport scaffold protein PDZK1, while downregulating uric acid reabsorbing proteins such as recombinant urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), and OAT4. In the intestine, SMP significantly increased the expression of PDZK1 and ABCG2. Additionally, SMP inhibited the protein expression of monosodium urate (MSU), NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase1. SMP also alleviated hyperuricemia-induced alterations in gut microbiota, particularly by modulating unclassified_f-Lachnospiraceae. The results indicate that SMP effectively attenuates inflammation and enhances uric acid metabolism, positioning it as a promising dietary intervention for hyperuricemia management.