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, cilt.34, sa.8, ss.5539-5563, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 34 Sayı: 8
- 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)
- Sayfa Sayıları: ss.5539-5563
- Anahtar Kelimeler: Osteoarthritis, Inflammation, REJENERA, ZeyEX (olive leaf extract), <italic>S</italic>-allylcysteine, Palmitoylethanolamide, NLRP3, Ibuprofen
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Osteoarthritis (OA) primarly involves the degradation of joint cartilage and requires new treatments. REJENERA©, a newly developed nutraceutical formula against OA, contains primarily olive leaf bioflavonoids (ZeyEX©, 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© (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-1β, IL-6, IL-10 and LPO in serum, and IL-6, TNF-α, and IFN-γ 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.