To explore the effects of Kaempferide on the NF-κB pathway and its role in cartilage cells of a rat model of rheumatoid arthritis (RA).

A rat model of collagen-induced arthritis (CIA) was used in this study. Twenty-four SD rats were randomly divided into four groups: control group, RA model group, low-dose Kaempferide group, and high-dose Kaempferide group, with 6 rats in each group. After treatment for four weeks, gross specimens of knee joints were observed in each group; cartilage conditions were examined by safranin staining; immunohistochemistry was used to detect the expression of MMP-13, Aggrecan, and NF-κB in cartilage tissue; and Western blot was performed to measure the expression of MMP-13, Aggrecan, and NF-κB in rat cartilage tissues. Rat joint cartilage cells were cultured in vitro, and their viability in the presence of different concentrations of Kaempferide was assessed by CCK8 assay. The cells were divided into control, IL-1β, low-dose Kaempferide, and high-dose Kaempferide groups, and qRT-PCR was used to detect the expression of IL-6 and MMP-13 in cartilage cells, and Western blot analysis was performed to measure the expression of IL-6, MMP-13, and NF-κB.

Compared to the control group, significant cartilage injury was observed in the RA group, which was mitigated by Kaempferide treatment at both low and high doses, with more significant effects observed in the high-dose group. Safranin staining showed that Kaempferide treatment significantly reduced cartilage injury in RA rats (P<0.05). Immunohistochemical results indicated that, in Kaempferide-treated RA rats, the expression of Aggrecan was significantly upregulated (P<0.05), while the expression of MMP-13 was significantly downregulated (P<0.05), especially in the high-dose Kaempferide group. Similarly, the expression of phosphorylated p65 was significantly reduced in the Kaempferide treatment groups (P<0.05), a finding also observed in Western blot analysis. CCK8 assay showed that Kaempferide at concentrations of 10 μM and 50 μM significantly enhanced the viability of IL-1β-treated rat cartilage cells (P<0.05). qRT-PCR revealed that after Kaempferide treatment, the mRNA expression levels of IL-6 and MMP-13 were significantly decreased in the RA cell model (P<0.05). Western blot results showed that after Kaempferide treatment, the protein expression levels of IL-6, MMP-13, and phosphorylated p65 were significantly decreased in the RA cell model (P<0.05).

Kaempferide can inhibit the activation of NF-κB, and reduce the production of IL-6 and MMP-13 in cartilage cells under inflammatory conditions, thereby decreasing cartilage inflammation and matrix degradation and playing a protective role in cartilage.