Diacerhein and Rhein Prevent Interleukin‐1β‐Induced Nuclear Factor‐κB Activation by Inhibiting the Degradation of Inhibitor κB‐α

Abstract

Diacerhein and rhein are anthraquinone compounds that ameliorate the course of osteoarthritis. Recent reports also suggest that these compounds may have antiinflammatory properties, but the cellular mechanisms by which they exert antiosteoarthritic and possibly antiinflammatory effects are still incompletely understood. The purpose of this study was to investigate the ability of diacerhein and rhein to inhibit the activation of the transcription factor nuclear factorkB, induced by the proinflammatory cytokine interleukin-1b, in primary monolayer cultures of bovine articular chondrocytes. We also studied the ability of diacerhein and rhein to prevent the expression of the inducible nitric oxide synthase gene, which is driven by nuclear factor-kB. We observed that interleukin-1b induced the degradation of the inhibitor kBa protein and the translocation of the protein p65 (a member of the nuclear factor-kB family) to the nucleus, which were inhibited by diacerhein and rhein, in a dose-dependent manner. Interleukin-1b-induced nuclear factor-kB binding to a specific (g-32 P)-labelled oligonucleotide probe was also inhibited by treatment of chondrocytes with diacerhein or rhein, as revealed by electrophoretic mobility shift assay. Inducible nitric oxide synthase mRNA and protein synthesis and nitric oxide production were also inhibited by diacerhein and rhein, in a dose-dependent manner. The half-maximal inhibitory concentrations of diacerhein and rhein, relative to nitric oxide production, were 8.2 mM and 7.7 mM, respectively. These results suggest that diacerhein and rhein inhibit nuclear factor-kB activation and, consequently, the expression of nuclear factor-kB-dependent genes, such as the inducible nitric oxide synthase gene, which can explain their antiosteoarthritic and antiinflammatory effects.

Comparative Analysis of Efficacy and Safety of Diacerein Versus S-Adenosyl Methionine in the Management of Osteoarthritis of Knee Joint

“…In vitro studies at the premembrane level reveal that diacerein and its active metabolite rhein down-regulate the activity of IL-1b by significantly decreasing the number of IL-1receptors on the cell surface, and by binding of IL-1 to its receptor significantly increasing the release of IL-1 receptor antagonist [17]. At the post-membrane level, diacerein inhibits the release of inflammatory and cartilage-degrading factors, inhibiting the activation of nuclear factor-kappa B [18]. It stimulates the production of cartilage growth factors such as transforming growth factor-beta and cartilage components, even in the presence of IL-1b [19].…”

Tratamento medicamentoso da osteoartrose do joelho

“…Atua principalmente pela inibição dos efeitos da IL-1 esta degrada a proteína inibidora do fator nuclear capa beta, que leva à transcrição de óxido nítrico, IL-1, TGF e metaloproteinases (26)(27)(28)(29) e também tem propriedades anabólicas, estimulando a produção de TGF-B e proteoglicanos, colágeno e ácido hialurônico (30) .…”

Diacerein the treatment of osteoarthritis

“…Внутриклеточно Д блокирует индуцируемую IL-1 актива-Основной фармакологический эффект симптоматических препаратов замедленного действия связан с воздействием на рецепторы сигнальных молекул и синтез провоспалительных медиаторов. Снижая интенсивность воспаления, они не только уменьшают боль, но и замедляют прогрессирование ОА цию транскрипционного фактора NFkB, снижая этим экс-прессию генов, ответственных за продукцию провоспали-тельных цитокинов: ФНО-α, IL-1, IL-6, оксида азота и металлопротеиназ (ММП), способствующих усиленному разрушению компонентов хрящевого матрикса [9].…”