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• W4284972953 abstract "Abstract Urolithin A (UA, 1 ), a gut microbiota postbiotic metabolite is attributed to express interesting biological activities indicated by in vitro, in vivo and clinical studies. Due to its strong anti-inflammatory properties it is considered as a promising lead molecule for further drug development, however, its strong phase II metabolism, severely limits its oral application. Therefore, monoesterified UA derivatives with selected NSAIDs: ibuprofen (Mix 3a / 3b ), mefenamic acid (Mix 4a / 4b ), diclofenac (Mix 5a / 5b ) and aspirin (Mix 6a / 6b ) were designed. Performed array of stability assays indicated Mix 4a / 4b as a most suitable candidate for further studies due to its exceptional stability in human plasma. Thus, we evaluated effects of Mix 4a / 4b on cell viability as well as the impact on cytokines secretion in THP-1 derived macrophages and compared it to UA. At high concentration (50 µM) Mix 4a / 4b expressed a cytotoxic effect, however at concentration of 5 µM it significantly suppressed TNF-α secretion, and significantly increased ani-inflammatory IL-10 secretion at 10 µM without affecting cell viability. This work has led to selection of a novel UA derivatives, which are stable in solutions and in human plasma as well as posess anti-inflammatory activity towards THP-1 macrophages at non-cytotoxic concentrations." @default.
• W4284972953 created "2022-07-10" @default.
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• W4284972953 date "2022-07-08" @default.
• W4284972953 modified "2023-09-25" @default.
• W4284972953 title "Conjugates of urolithin A with NSAIDs, their stability, cytotoxicity, and anti-inflammatory potential" @default.
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• W4284972953 doi "https://doi.org/10.1038/s41598-022-15870-8" @default.
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