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REJENERA\n                    <jats:sup>\u00a9<\/jats:sup>\n                    , a newly developed nutraceutical formula against OA, contains primarily olive leaf bioflavonoids ( ZeyEX\n                    <jats:sup>\u00a9<\/jats:sup>\n                    , quercetin and luteolin),\n                    <jats:italic>S<\/jats:italic>\n                    -allylcysteine, palmitoylethanolamide,\n                    <jats:sc>l<\/jats:sc>\n                    -proline, hyaluronic acid and boron. This study focuses on the efficacy of REJENERA in treating knee OA and aims to compare it with ZeyEX, NPROC\n                    <jats:sup>\u00a9<\/jats:sup>\n                    (a product obtained by combining collagen-rich eggshell membrane with olive leaf extract), and IBUPROFEN in a rat OA model. OA was established by intra-articular injection of monosodium iodoacetate (MIA; 3\u00a0\u00a0mg) into the right knee joints. Rats were either left untreated or treated orally for 12\u00a0weeks with REJENERA, ZeyEX, NPROC (300\u00a0mg\/kg\/day) or IBUPROFEN (3\u00a0mg\/kg\/day). MIA injection produced joint degeneration including increased fissure-index, osteophyte-score, and OARSI-score, joint swelling, synovial inflammation, proteoglycan loss, and decreased cartilage thickness. These histopathological abnormalities were partially but significantly alleviated by REJENERA and other treatments. Only ZeyEX significantly inhibited the OA-induced increase in IL-1\u03b2, IL-6, IL-10 and LPO in serum, and IL-6, TNF-\u03b1, and IFN-\u03b3 in synovial fluid. While increases in MMP-3 and MMP-9 were reduced with all treatments, MMP-13 was inhibited only by REJENERA. ZeyEX increased IL-2, NPROC increased IL-6, and IBUPROFEN inhibited IL-10. All treatments improved TIMP-1 levels; however, TXNIP was more significantly inhibited by ZeyEX, and NLRP3 by REJENERA. REJENERA\u2019s anti-OA effects are accompanied by an increase in cartilage anabolic factors (Ki-67, type-II collagen, BMP-7) and inhibition of apoptosis. REJENERA offers a promising multi-targeted therapeutic approach to treating OA by blocking the iNOS-TXNIP-NLRP3\u00a0signaling axis, and reducing oxidative stress.\n                  <\/jats:p>","DOI":"10.1007\/s10787-026-02314-2","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T04:36:56Z","timestamp":1783312616000},"page":"5539-5563","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["REJENERA\u00a9, a multi-component bioflavonoid-based formula, alleviates osteoarthritis and provides chondroprotection by regulating the NLRP3-TXNIP-iNOS axis and inflammation: a comparative study with olive leaf nutraceuticals and ibuprofen"],"prefix":"10.1007","volume":"34","author":[{"given":"Huseyin Emre","family":"Tepedelenlioglu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zubeyir","family":"Elmazoglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanem Gulistan","family":"Saribas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yildiz","family":"Tutuncu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asli F.","family":"Ceylan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0954-8465","authenticated-orcid":false,"given":"\u00c7imen","family":"Karasu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"issue":"9","key":"2314_CR1","doi-asserted-by":"publisher","first-page":"488","DOI":"10.3390\/metabo14090488","volume":"14","author":"R Altahla","year":"2024","unstructured":"Altahla R, Tao X (2024) Thioredoxin-interacting protein\u2019s role in NLRP3 activation and osteoarthritis pathogenesis by pyroptosis pathway. 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