REJENERA, 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
INFLAMMOPHARMACOLOGY, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s10787-026-02314-2
- Dergi Adı: INFLAMMOPHARMACOLOGY
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO), Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Health Research Premium Collection (ProQuest)
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Gazi Üniversitesi Adresli: Evet
Özet
Osteoarthritis (OA) primarly involves the degradation of joint cartilage and requires new treatments. REJENERA (c), a newly developed nutraceutical formula against OA, contains primarily olive leaf bioflavonoids ( ZeyEX (c), quercetin and luteolin), S-allylcysteine, palmitoylethanolamide, l-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 (c) (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 mg) into the right knee joints. Rats were either left untreated or treated orally for 12 weeks with REJENERA, ZeyEX, NPROC (300 mg/kg/day) or IBUPROFEN (3 mg/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 beta, IL-6, IL-10 and LPO in serum, and IL-6, TNF-alpha, and IFN-gamma 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's 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 signaling axis, and reducing oxidative stress.