Anti-inflammatory effects of valdecoxib found in Clonorchis sinensis excretory/secretory products in an Ankylosing Spondylitis

Clonorchis sinensis, a liver fluke, secretes immunomodulatory molecules that may suppress inflammation in autoimmune diseases such as ankylosing spondylitis (AS). However, the specific bioactive compounds involved remain largely unidentified. We performed LC-MS/MS-based metabolomic profiling of CS-ESP and detected a compound identical to valdecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, as a candidate bioactive molecule. Then, we evaluated therapeutic efficacy of valdecoxib in curdlan-induced AS mice. Clinical arthritis scores, paw thickness, and joint histopathology were assessed. In vitro cytotoxicity was tested using an MTS assay in both RAW 264.7 cells and peripheral blood mononuclear cells (PBMCs) obtained from AS patients. Valdecoxib showed no significant cytotoxicity to RAW cells until at 15 μg/ml and to AS PBMCs until at 200 μg/ml, respectively. In the SKG mouse model, valdecoxib treatment effectively delayed the development of arthritis and significantly reduced its severity (clinical scores of disease control group vs. valdecoxib group, mean ± SEM; 5.28 ± 1.00 vs. 3.84 ± 1.08, p < 0.05). Histological evaluation showed reduced arthritis (Histopathology scores of the ankles, mean ± SD; negative control group vs. disease control group: 0.50 ± 0.45 vs. 9.33 ± 4.55, p < 0.001; disease control group vs. valdecoxib group: 9.33 ± 4.55 vs. 4.75 ± 0.76, p < 0.05) in mice treated with valdecoxib. The current study showed that a compound identical to valdecoxib detected in CS-ESP exhibited robust anti-inflammatory and joint-protective effects in an AS model and highlighted the need for investigation into the chemical identity and immunoregulatory mechanisms of CS-ESP metabolites.