Objective - To test the hypothesis that simulated digests of Biota orientalis (BO) and a dietary nutraceutical (DN; composed of mussel, shark cartilage, abalone, and BO seed lipid extract) inhibit prostaglandin E2 (PGE2), nitric oxide (NO), and glycosaminoglycan (GAG) production in interleukin (IL)-1-stimulated cartilage explants. Sample Population - Cartilage tissue from 12 pigs. Procedures - Articular cartilage explants were conditioned with a simulated digest of BO (BOsim) or DN (DNsim) at concentrations of 0, 0.06, or 0.18 mg/mL or indomethacin (INDO sim; 0 or 0.02 mg/mL) for 72 hours. Control explants received digest vehicle only. Explants were or were not stimulated with recombinant human-IL-1β (10 or 0 ng/mL) during the final 48 hours of culture. Concentrations of PGE2, GAG, and NO in media samples (mPGE2, mGAG, and mNO concentrations, respectively)-were analyzed, and explant tissue was stained fluorochromatically to determine chondrocyte viability. Treatment effects during the final 48-hour culture period were analyzed. Results - IL-1 increased mPGE2, mGAG, and mNO concentrations in control explants without adversely affecting cell viability. Treatment with INDOsim blocked PGE2 production and increased mNO concentration in IL-1-stimulated and unstimulated explants and increased mGAG concentration in unstimulated explants. Treatment with DNsim (0.06 and 0.18 mg/mL) reduced mPGE2 concentration in IL-1-stimulated and unstimulated explants, reduced mNO concentration in IL-1-stimulated explants, and increased mNO concentration in unstimulated explants. Treatment with 0.18 mg of DNsim/mL increased cell viability in the presence of IL-1. In IL-l-stimulated explants, BOsim (0.06 and 0.18 mg/mL) reduced mPGE2 concentration, but 0.18 mg of BOsim/mL increased cell viability. Conclusions and Clinical Relevance - Effects of IL-1 on cartilage explants in vitro were modulated by DNsim and BOsim.