Ellagic acid improves osteoarthritis by inhibiting PGE2 production in M1 macrophages via targeting PTGS2

• DOI: 10.1111/1440-1681.13918
• Publication Date: 2024-08-27T05:11:07Z
• Authors: Chen Zhang; Xiaoke Li; Pengyuan Wen; Yuan Li
• Keywords: Ellagic Acid

Abstract Osteoarthritis (OA) is a degenerative joint disease characterised by inflammation and cartilage degeneration. Ellagic acid (EA) might have therapeutic potential in OA, but its molecular mechanisms of action remain unclear. In this study, we aimed to identify the docking protein EA M1 macrophage‐related pro‐inflammation OA. Bioinformatics analysis was performed ellagic acid's targets among OA‐related dysregulated genes. THP‐1 cells were induced into M0 polarised macrophages for vitro studies. Mice knee models OA generated vivo Results showed that PTGS2 (also known as COX‐2) target has multiple low‐energy binding sites on PTGS2, including containing amino residues critical enzyme's catalytic activity. Surface plasmon resonance (SPR) assays confirmed physical interaction between recombinant protein, with dissociation constant (KD) 5.03 ± 0.84 μM. treatment suppressed expression prostaglandin E2 (PGE2) production macrophages. Besides, can directly inhibit enzyme activity, an IC50 around 50 Importantly, mouse model administration alleviated severity, reduced collagen II degradation MMP13 generation, decreased serum PGE2 levels. Collectively, these results suggest key anti‐inflammatory chondroprotective effects