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And Osteoarthritis (OA) is one of the most common degenerative diseases in clinical medicine. Currently, anti-inflammatory drugs and intra-articular drug injection are mainly used, but the treatments only relieve symptoms. Punicalagin (PUN), a hydrolyzable tannin derived from pomegranate extract, the suppression of pro-inflammatory cytokine production in macrophages. The therapeutic potential of PUN in alleviating inflammatory osteolysis remains inadequately elucidated. PUN demonstrated favourable biocompatibility and therapeutic potential in vitro, including potent anti-osteoclastic activity, ROS scavenging capacity, and epigenetic regulatory functions. PUN was found to inhibit bromodomain-containing protein 4 (Brd4)-mediated chromatin space remodeling, consequently upregulating the production of endogenous anti-inflammatory factors and antioxidant factors. This study reveals a new therapeutic mechanism that PUN exerts anti-inflammatory effects and regulates epigenetic regulation by influencing Brd4-mediated chromatin remodeling. These findings showed the therapeutic potential of PUN for inflammatory diseases, especially inflammatory osteolysis. Notably, our work identifies a new strategy that synergistically combines osteoclast inhibition with epigenetic regulation, providing a promising direction for the therapies for bone-related inflammatory diseases.<\/jats:p>","DOI":"10.1038\/s41598-026-41262-3","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T14:47:32Z","timestamp":1773154052000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Punicalagin with anti-inflammatory activities affects Brd-4 mediated chromatin remodeling for attenuating inflammatory osteolysis"],"prefix":"10.1038","volume":"16","author":[{"given":"Huiping","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qilin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhao","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yexin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanyong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"issue":"5","key":"41262_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0540-y","volume":"9","author":"H Wu","year":"2018","unstructured":"Wu, H. et al. 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