Conjugates of urolithin A with NSAIDs, their stability, cytotoxicity, and anti-inflammatory potential
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 developme...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-15870-8 |
| _version_ | 1828775069005905920 |
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| author | Maciej Korczak Piotr Roszkowski Sebastian Granica Jakub P. Piwowarski |
| author_facet | Maciej Korczak Piotr Roszkowski Sebastian Granica Jakub P. Piwowarski |
| author_sort | Maciej Korczak |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T15:32:33Z |
| format | Article |
| id | doaj.art-8ade1e4cf42e4ca8b1716f34df24c26d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-11T15:32:33Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-8ade1e4cf42e4ca8b1716f34df24c26d2022-12-22T01:00:01ZengNature PortfolioScientific Reports2045-23222022-07-0112111510.1038/s41598-022-15870-8Conjugates of urolithin A with NSAIDs, their stability, cytotoxicity, and anti-inflammatory potentialMaciej Korczak0Piotr Roszkowski1Sebastian Granica2Jakub P. Piwowarski3Microbiota Lab, Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of WarsawLaboratory of Natural Products Chemistry, Faculty of Chemistry, University of WarsawMicrobiota Lab, Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of WarsawMicrobiota Lab, Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of WarsawAbstract 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.https://doi.org/10.1038/s41598-022-15870-8 |
| spellingShingle | Maciej Korczak Piotr Roszkowski Sebastian Granica Jakub P. Piwowarski Conjugates of urolithin A with NSAIDs, their stability, cytotoxicity, and anti-inflammatory potential Scientific Reports |
| title | Conjugates of urolithin A with NSAIDs, their stability, cytotoxicity, and anti-inflammatory potential |
| title_full | Conjugates of urolithin A with NSAIDs, their stability, cytotoxicity, and anti-inflammatory potential |
| title_fullStr | Conjugates of urolithin A with NSAIDs, their stability, cytotoxicity, and anti-inflammatory potential |
| title_full_unstemmed | Conjugates of urolithin A with NSAIDs, their stability, cytotoxicity, and anti-inflammatory potential |
| title_short | Conjugates of urolithin A with NSAIDs, their stability, cytotoxicity, and anti-inflammatory potential |
| title_sort | conjugates of urolithin a with nsaids their stability cytotoxicity and anti inflammatory potential |
| url | https://doi.org/10.1038/s41598-022-15870-8 |
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