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-1β-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-1β, 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-1β-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-α, 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.

Combinations of IL-1β and other proinflammatory cytokines reportedly promote the severity of arthritis. We aimed to investigate the effects of IL-1β combined with IL-17A on cartilage degradation and synthesis in in vitro models. Cartilage explant degradation was determined using sulfated glycosaminoglycans (S-GAGs) levels, matrix metalloproteinase (MMP13) gene expression, uronic acid, and collagen contents. Cell morphology and accumulation of proteoglycans were evaluated using hematoxylin-eosin and safranin O staining, respectively. In the pellet culture model, expressions of cartilage-specific anabolic and catabolic genes were evaluated using real-time qRT-PCR. Early induction of MMP13 gene expression was found concomitantly with significant S-GAGs release. During the prolonged period, S-GAGs release was significantly elevated, while MMP-13 enzyme levels were persistently increased together with the reduction of the cartilaginous matrix molecules. The pellet culture showed anabolic gene downregulation, while expression of the proinflammatory cytokines, mediators, and MMP13 genes were elevated. After cytokine removal, these effects were restored to nearly basal levels. This study provides evidence that IL-1β combined with IL-17A promoted chronic inflammatory arthritis by activating the catabolic processes accompanied with the suppression of cartilage anabolism. These suggest that further applications, which suppress inflammatory enhancers, especially IL-17A, should be considered as a target for arthritis research and therapy.

Ongchai S, et al. J Vet Sci. 2018 Nov;19(6):735-743. https://doi.org/10.4142/jvs.2018.19.6.735

Senna species and anthraquinone derivatives generated by these organisms, rhein and aloe-emodin, exert anti-inflammatory effects. These species present a similar morphology but produce different ingredients when they are used as medicinal products. In this study, a DNA barcoding- (Bar-) high-resolution melting (HRM) technique was developed using internal transcribed sequence 2 (ITS2) to differentiate between Senna alata and Senna tora as a result of significant differences in their melting profiles. We used this approach for confirmation of S. alata and S. tora raw materials, and we examined the chondroprotective properties of the ethanolic extracts of S. alata and S. tora using a porcine model of cartilage degradation induced by a combination of interleukin-17A (IL-17A) and IL-1β. We found that both Senna ethanolic extracts, at a concentration of 25 μg/mL, effectively prevented cartilage degradation. Rhein and aloe-emodin were present in the extract of S. alata but not in that of S. tora. We observed a reduction in the release of sulfated glycosaminoglycans (S-GAGs) and hyaluronic acid (HA) into media in both treatments of Senna extracts, which indicated proteoglycan preservation in explant tissues. These results suggest that neither rhein nor aloe-emodin are the main factors responsible for cartilage-protecting properties. Taken together, results show that both S. alata and S. tora are promising for further development as anti-osteoarthritic agents and that Bar-HRM using ITS2 could be applied for species confirmation with Senna products.