THESIS
2021
1 online resource (vii, 51 pages) : illustrations (some color)
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 medi...[
Read more ]
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.
Post a Comment