Establishment and characterization of a novel cell model for anti-gout medicine screening and testing using needle-like uric acid crystals to induce inflammation responses

Abstract

This research aimed to develop a novel cell model for gout medicine screening and testing. In the human body, accumulation of uric acid crystals results in gout, and uric acid crystals are formed mainly due to excessive uric acid precipitating in the joint areas. Uric acid crystallizes to trigger immune response through NLRP3 inflammasome activation, resulting in serious gout pain. The current medicines for gout prevention and acute gout pain treatment are not satisfactory. The first type of medicine focuses on uric acid lowering to reduce the gout attack frequency but is not able to prevent the gout onset. The second type of drugs are painkillers, which only suppress the pain but cannot cure gout or increase uric acid crystals’ resolution. To establish a better cell model for gout medicine screening and testing, needle-like uric acid crystals were generated under a homothermic environment. The uric acid crystals were applied to HEK293T cells, and they induced more profound immune response than soluble uric acid. Moreover, the increased dissolution of uric acid crystals by cells was observed, and this was used for the evaluation of anti-gout activities of drug candidates. Subsequently, three herbal extracts, Astragali Radix (AR), Lilii Bulbus (LB), and Poria cocos (PC), were tested using the novel drug screening method. AR and PC increased uric acid transportation and dissolution, and PC suppressed the inflammation induced by uric acid crystals. The novel cell model for gout medicine screening and testing has been established in this study for discovering the next-generation gout medicines.

Date of Award	2021
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Chun LIANG (Supervisor)