Effects of Luteolin on an MIA-Induced Osteoarthritis Rat Model via Reducing IL-18

Background/Aims: Luteolin (LUT), a flavone abundant in Reseda luteola, possesses well-documented anticancer, antioxidant, and anti-inflammatory properties. This study aimed to investigate whether LUT attenuates osteoarthritis (OA) progression by suppressing interleukin (IL)-18 expression in a monosodium iodoacetate (MIA)-induced OA rat model.

Materials and Methods: Osteoarthritis was induced by intra-articular injection of MIA. Luteolin and celecoxib (CLX) were administered orally once daily for 2 weeks, beginning 2 weeks after MIA injection (n = 6 per group). Pain-related behaviors were evaluated using weight-bearing and von Frey tests. Structural pathology was assessed using hematoxylin and eosin (H&E), Safranin O, and Toluidine Blue staining, followed by modified Mankin scoring. Interleukin-18 expression was quantified in serum and articular cartilage using immunohistochemistry and quantitative realtime polymerase chain reaction (qRT-PCR).

Results: Luteolin significantly increased the weight-bearing ratio and mechanical withdrawal threshold. Luteolin also showed a trend toward attenuating cartilage damage and reducing modified Mankin scores, although these effects were not statistically significant. In addition, LUT significantly reduced the number of IL-18-positive chondrocytes in cartilage and showed a tendency to decrease IL-18 mRNA expression and serum IL-18 concentrations. These effects were comparable to those observed with CLX treatment.

Conclusion: This study provides preclinical evidence that LUT may exert anti-inflammatory and chondroprotective effects in MIA-induced OA, potentially through modulation of IL-18. These findings support further investigation of LUT as a potential therapeutic candidate for OA.

Cite this article as: Kim JH, Lee SH, Lee YJ, Song JY, Gil HH, Lee J. Effects of luteolin on an MIA-induced osteoarthritis rat model via reducing IL-18. ArchRheumatol. Published online July 03, 2026. doi: 10.5152/ArchRheumatol.2026.25143.