ABSTRACT: Sunflower (Helianthus annuus L.) calathide is becoming more well-known as a result of its anti-hyperuricemia bioactivity. Aiming at developing anti-hyperuricemic ingredients in sunflower calathide extract (SCE), we were fortunate to discover abietic acid (AA), identified from SCE, has the capacity to inhibit xanthine oxidase activity at low concentrations (IC50 = 10.60 µM and inhibition constant was 193.5 nM) that examined by inhibitor screening experiment in vitro and computer-simulated molecular docking. To further explore the anti-hyperuricemia effects, the UA-stimulated human embryonic kidney (HEK) 293T cells were evaluated as a conceivable model in the current study. The huge amounts of high-throughput sequencing data, which mapping to reference genome, were analyzed by bioinformatics approaches: Weighted Gene Co-Expression Network Analysis (WGCNA) along with Kyoto Encyclopedia of Genes and Genomes (KEGG). Interestingly, the purine metabolism-related genes expressed in the AA treatment were nearly opposite to that of the UA group, indicating negative feedback regulations that AA perhaps contributes to maintain urate homeostasis in the high UA-exposed kidney cellular environment. Here, we consider that HEK293T cells ought to be an achievable in vitro model for UA metabolism research because the PNPase, PRPS1, PRPS2, and RPIA, which participate in UA generation, widely expressed in the untreated 293T cells as well. And AA markedly suppressed the PNPase, PRPS2, and RPIA expressed in UA-stimulated 293T cells, implying inhibitions for UA biosynthesis. As a result, AA not only inhibited xanthine oxidase activity efficiently but also regulated genes PNPase, PRPS2, and RPIA. It is promising to be developed as an inhibitor against hyperuricemia. Therefore, abietic acid, which could be isolated from plants, has the potential for anti-hyperuricemia, and the current study provided a precedent for pharmacology analysis of natural ingredients.
