{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:38:22Z","timestamp":1760146702946,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FU 408\/11-1"],"award-info":[{"award-number":["FU 408\/11-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Activation of inflammatory pathways releases a storm of cytokines. Moreover, unregulated cytokines contribute to chronic inflammatory disorders. However, ligand-activated peroxisome proliferator-activated receptor gamma (PPAR\u03b3) is involved in suppressing inflammatory cytokines via transrepression of nuclear factor kappa B (NF\u03baB). Therefore, in this study, the anti-inflammatory saponin DT-13 is explored as a ligand of PPAR\u03b3. DT-13 upregulated the expression of PPAR\u03b3 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in comparison to treatment with LPS alone. Applying a HEK transfection model, we observed a DT-13 dose-dependent increase in ligand-dependent activation of PPAR\u03b3, which was compared with troglitazone and rosiglitazone. DT-13 was not able to compete with the synthetic fluoromone tracer for binding to PPAR\u03b3 as observed in a fluorescence polarization binding assay, whereas molecular docking showed a possible binding interaction of DT-13 with the PPAR\u03b3 nuclear receptor. We proved the expression of PPAR\u03b3 protein in the presence of DT-13 using a robust cell-based HEK293FT transfection model. More in-depth analysis needs to be performed to evaluate the efficiency of the binding of DT-13 to PPAR\u03b3. A possible binding interaction of DT-13 to PPAR\u03b3 was observed, similar to that of rosiglitazone. This study revealed a novel mechanism for anti-inflammatory effects by DT-13 through PPAR\u03b3-dependent transrepression of NF\u03baB.<\/jats:p>","DOI":"10.3390\/biology13121015","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T10:07:10Z","timestamp":1733306830000},"page":"1015","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["DT-13 Mediates Ligand-Dependent Activation of PPAR\u03b3 Response Elements In Vitro"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4060-9219","authenticated-orcid":false,"given":"Shikha","family":"Raina","sequence":"first","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Institute of Diagnostic Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Augustenburger Platz 1, D-13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6295-1202","authenticated-orcid":false,"given":"Esther","family":"Samuel","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Institute of Diagnostic Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Augustenburger Platz 1, D-13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9153-9594","authenticated-orcid":false,"given":"Hendrik","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Institute of Diagnostic Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Augustenburger Platz 1, D-13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature07201","article-title":"Origin and physiological roles of inflammation","volume":"454","author":"Medzhitov","year":"2008","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"King, T.C. 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