## 4 Discussion
OA-induced rabbits exhibited significant decreases in AC thickness of the femur and tibia. It is also reported that the number of chondrocytes significantly increased synovial IL-1\(\beta\), IL-6, and TNF-\(\alpha\) levels and significantly increased numbers of femoral and tibial subchondral IL-1\(\beta\) and TNF-\(\alpha\)-immunolabeled cells [42]. In this trial, treatment of PS favorably inhibited surgically induced OA through anti-inflammatory and AC preserving effects (Figure 3). The inflammatory cytokine (IL-1\(\beta\) IL-6, TNF-\(\alpha\)) levels increased in the NC group versus those of the normal control CON group. Conversely, these OA-induced symptoms of inflammation were significantly inhibited by 12 weeks of supplement with PS (100 and 300 mg/kg body weight). PS decreased the release of IL-1\(\beta\), IL-6, and TNF-\(\alpha\) into the serum of OA rats. These findings represent reliable evidence that PS has favorable anti-inflammatory effects on surgically induced OA rats, and these results are consistent with the report showing a strong correlation between low inflammatory levels and anti-osteoarthritis effects in animals supplemented with functional foods [22; 25]. MMPs are involved in the degradation of the ECM [42], although their expression can be suppressed by metalloprotein inhibitors [43]. The MMPs are reliable predictors of cartilage loss during the development of OA [44], and their increase has been reported in the synovium and chondrocytes of surgically induced OA models [45]. Lipocalin-2 is believed to play a significant functional role in OA cartilage [46] as a biomarker for cartilage degradation in arthritic disease [47], although [PERSON] and [PERSON] suggested that its upregulation in osteoarthritic cartilage is not necessary for cartilage destruction in mice [16]. In this study, we found that PS decreased serum MMP-2, MMP-7, MMP-9, MMP-13, and lipocalin-2 levels when administered at a dose of 100 or 300 mg/kg (\(p<0.05\)) compared with those of the NC group. After treating the rats with PC, weak effects on the serum MMP-2, -3, -7, -8, and lipocalin-2 levels of OA rats were observed (\(p>0.05\)). It is interesting that PS improved the biomarkers such as MMP-2, -7, and lipocalin-2 in a dose-dependent manner and was more effective than diclofenac sodium salt for the PC group. Furthermore, not only Plebeian age extracted with 95% \(v/v\) EtOH at 70 \({}^{\circ}\)C [33] but also Plebeian age extracted with 50% \(v/v\) EtOH at room temperature effectively inhibited osteoarthritis. This is a great news to customers and health food producers with its low producing price and higher safety. Thus, the PS used in this study may be used widely for osteoarthritis treatment with lower prices and improved safety. iNOS is induced by pro-inflammatory cytokines and is involved in high levels of NO production during the inflammatory process [48; 49]. NF-kB proteins constitute a family of transcription factors stimulated by pro-inflammatory cytokines, chemokines, stress-related factors, and ECM degradation products. The activated NF-kB molecules trigger the expression of genes that induce destruction of the articular joint [10]. The activation of stress- and inflammation-induced signaling, transcriptional, and posttranscriptional events may cause a phenotypic shift, apoptosis, and aberrant expression of inflammation-related genes, including catabolic genes [25]. These include nitric oxide synthase (NOS)-2, cyclooxygenase (COX)-2, and several matrix metalloproteinases (MMPs) [26; 45]. In this study, we evaluated whether PS could ameliorate inflammation and cartilage degradation in surgically induced osteoarthritis rats. Extended evaluation should be performed by measuring joint pain of experimental animals and by studying chondrocytes and synovioocytes to verify its effects on controlling pro-inflammatory cytokines, chemokines, and stress-related factors.