Suppression of Cartilage Degradation by Zingerone Involving the p38 and JNK MAPK Signaling Pathway

Abstract

Zingerone, an active compound that is present in cooked ginger, has been claimed to be a bioactive ingredient that holds the potential of preventing and/or treating diseases involving inflammation. In this study, zingerone was used to discover its properties against joint inflammation using interleukin-1-induced osteoarthritis in cartilage explant and cell culture models. Zingerone was supplemented into the cartilage explant and cell culture media at different concentrations along with the presence of interleukin-1, an inducer of osteoarthritis. Markers indicating cartilage degradation, inflammation, and the signaling molecules involved in the inflammatory induction were investigated. Diacerien, an anti-osteoarthritic drug, was used as a positive control. Zingerone at a concentration of 40 µM reduced the level of matrix metalloproteinase-13 to about 31.95 ± 4.33 % compared with the interleukin-1-treated group and halted cartilage explant degradation as indicated by reducing the accumulative release of sulfated glycosaminoglycans by falling to the control concomitantly with an elevation of the remaining contents of uronic acid and collagen in the explant tissues when zingerone was added. In the SW1353 cell line model, zingerone efficiently suppressed the expression of TNF-, interleukin-6, and interleukin-8 mRNA levels and tended to reduce the levels of both p38 and c-Jun N-terminal kinase phosphorylation. From the results of this study, it can be concluded that zingerone potentially reduced cartilage degradation, which is partially involved in p38 and c-Jun N-terminal kinases of the mitogen activator protein kinase signaling pathway leading to the reduction of proinflammatory cytokine amplification effects and cartilage-degrading enzyme syntheses. This finding supports the contention that ginger holds positive pharmaceutical effects against osteoarthritis.

The mechanism of TDP‐43 gene expression on inflammatory factors and the JNK and p38 MAPK signalling pathways in ischaemic hypoxic stress dependence

“…19 Ruangsuriya et al found that JNK and p38 MAPK phosphorylation was related to secondary OA after trauma. 9 This study also confirmed that the expression levels of JNK and p38 MAPK in the cartilage tissues of rats in the OA model group were significantly higher than those of the control group. However, after TDP-43-mMSCs were transplanted into the OA model rats, the expression levels of JNK and p38 MAPK in the cartilage tissues of rats were significantly lower than those of the model group.…”

“…Bo et al confirmed that the activation of JNK and P38 MAPK could cause the calcification, hypertrophy, and apoptosis of chondrocytes in the articular cartilage of OA patients and participate in the imbalance of degradation and synthesis of chondrocytes . Ruangsuriya et al found that JNK and p38 MAPK phosphorylation was related to secondary OA after trauma . This study also confirmed that the expression levels of JNK and p38 MAPK in the cartilage tissues of rats in the OA model group were significantly higher than those of the control group.…”

“…In addition, studies by Joos et al have shown that p38 MAPK activation can cause pain in the patient's joints and lead to malignant circulation in the internal environment of articular cartilage . Phosphorylated Jun N‐terminal kinase (JNK) increases the expression of matrix metalloproteinase through its downstream transcription factors, leading to progressive degradation of the chondrocyte extracellular matrix …”

“…8 Phosphorylated Jun N-terminal kinase (JNK) increases the expression of matrix metalloproteinase through its downstream transcription factors, leading to progressive degradation of the chondrocyte extracellular matrix. 9 Mesenchymal stromal cells (MSCs) are a group of homogenous cells with the potential of multidirectional differentiation, which have an effective anti-inflammatory effect. Especially in the treatment of rheumatic diseases, the anti-inflammatory effect of MSCs has been confirmed.…”

Hyperbaric oxygen protects type II collagen in interleukin-1β-induced mandibular condylar chondrocyte via inhibiting the JNK/c-Jun signaling pathway

“…Previous researches have shown that the JNK/c-Jun signaling pathway was activating by inflammatory factors and the inhibition of it could suppress the cartilage degradation [ 35 , 36 ]. The activation of JNK/c-Jun signaling pathway results in the expression of MMPs and then breaks chondrocytes of cartilage [ 37 ].…”