Discovery and Characterization of Moracin C as an Anti-Gouty Arthritis/Hyperuricemia Candidate by Docking-Based Virtual Screening and Pharmacological Evaluation.

In the present study, a natural product database of compounds associated with herbs traditionally verified to treat gout/hyperuricemia/arthritis was constructed. 3D-shape and docking-based virtual screening was conducted. To identify potential xanthine oxidase (XOD) inhibitors in the database, eight compounds with commercial availability were identified as high 3D-shape similarity with febuxostat (), a known XOD inhibitor. Docking was used to further predict the possible interactions between XOD and these compounds. Moracin C (), moracin D (), and isoformononetin () exhibited higher docking scores and binding energies than other compounds. In vitro, inhibited XOD with an IC value of 0.25 ± 0.14 μM, which is similar to that of (0.16 ± 0.08 μM). In a hyperuricemic mouse model, 5-20 mg/kg exhibited satisfying urate-lowering and XOD inhibitory effects. Compound also exhibited antiarthritis activities. In RAW264.7 cells, at 1-10 μM inhibited the expression of IL-1β and TNF-α induced by MSU. In an acute gouty arthritis model in SD rats, 5-20 mg/kg significantly alleviated the toe swelling, inflammatory response, and dysfunction disorder caused by monosodium urate (MSU). Compound inhibited serum IL-1β and TNF-α cytokines as well as reduced the expression of the NLRP3/ASC/caspase-1 inflammasome in joints. In summary, was an effective compound for the treatment of hyperuricemia/gouty arthritis.