Gout is an inflammatory arthritis characterized by abrupt self-limiting attacks of inflammation caused by precipitation of monosodium urate crystals (MSU) in the joint. Both anti-hyperuricemia and anti-inflammation could be gout therapeutic strategies, whereas ideal drugs for gout treatment are deficient.
4-(2-(4-chlorophenyl)-1-((4-chlorophenyl)amino)ethyl)benzene-1, 3-diol (CBED) was obtained from a cluster of deoxybenzoins derivatives synthesized by our research group with potent anti-hyperuricemic and anti-inflammatory activities, which was expected to be a dual inhibitor of xanthine oxidase (XOD) and NOD-like receptor protein 3 (NLRP3). This study aimed to investigate effects of CBED on XOD and NLRP3 in vitro, as well as the possible mechanisms by which CBED improved gout in vivo.
After molecular docking detection, inhibitory effects of CBED on XOD and NLRP3 were evaluated in vitro. Subsequently, hyperuricemia and acute gouty arthritis animal models were established by potassium oxonate or MSU, respectively. After CBED treatment, serum uric acid levels, synovial interleukin (IL)-1β concentrations, hepatic XOD activities, as well as synovial morphological changes were examined. More importantly, synovial expressions of NLRP3 inflammasome components including NLRP3, apoptosis-associated speck-like protein (ASC) and caspase-1 in rats were analyzed by immunofluorescence and western blot.
In vitro, CBED obviously inhibited XOD activity with an IC
CBED might serve as a dual XOD and NLRP3 inhibitor for treatment of gout.