Curcumin synergizes with resveratrol to stimulate the MAPK signaling pathway in human articular chondrocytes in vitro

Abstract

The mitogen-activated protein kinase (MAPK) pathway is stimulated in differentiated chondrocytes and is an important signaling cascade for chondrocyte differentiation and survival. Pro-inflammatory cytokines such as interleukin 1b (IL-1b) play important roles in the pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA). In this study, we investigated whether curcumin and resveratrol can synergistically inhibit the catabolic effects of IL-1b, specifically the inhibition of the MAPK and subsequent apoptosis in human articular chondrocytes. Chondrocytes were either left untreated or treated with 10 ng/ml IL-1b or 1 lM U0126, a specific inhibitor of MAPK pathway alone for the indicated time periods or pretreated with 10 lM curcumin, 10 lM resveratrol or 10 lM resveratrol and 10 lM curcumin for 4 h followed by cotreatment with 10 ng/ml IL-1b or 1 lM U0126 and 10 lM resveratrol, 10 lM curcumin or 10 lM resveratrol and 10 lM curcumin for the indicated time periods. Cultures were evaluated by immunoblotting and transmission electron microscopy. Incubation of chondrocytes with IL-1b resulted in induction of apoptosis, downregulation of b1-integrins and the extracellular signal-regulated kinase 1/2 (Erk1/2). Interestingly, U0126 induced apoptosis and blocked the above-mentioned proteins in a similar way to IL-1b. Furthermore, curcumin and resveratrol inhibited IL-1b-or U0126-induced apoptosis and downregulation of b1-integrins and Erk1/2 in human articular chondrocytes. These results suggest that combining these two natural compounds activates MEK/Erk signaling, a pathway that is involved in the maintenance of chondrocyte differentiation and survival.

Sirtuin-1 (SIRT1) Is Required for Promoting Chondrogenic Differentiation of Mesenchymal Stem Cells

“…SIRT1 has regulatory effects on cell differentiation, proliferation, survival, and organism longevity (47, 54 -56). Furthermore, our laboratory and others have previously reported that resveratrol is an inhibitor of the pro-inflammatory cytokine IL-1␤, highlighting that resveratrol suppressed IL-1␤-induced activation of NF-B and NF-B-dependent gene products (51,57,58). Indeed, we have also shown that resveratrol inhibited IL-1␤-induced apoptosis in tenocytes, and this was linked to changes in the expression of p53, Bax, and caspase-3 (38).…”

Effects of Three Kinds of Curcuminoids on Anti-Oxidative System and Membrane Deformation of Human Peripheral Blood Erythrocytes in High Glucose Levels

“…The erythrocyte suspension was pre-incubated with the three kinds of curcuminoids for 4 h before the glucose was added [1]. After pre-incubation, the two concentrations of glucose were added in different groups, the cell suspension was continually incubated for 20 h in a shaking water bath at 37°C.…”

“…Indeed, turmeric has been used in traditional ayurvedic and chinese medicine since 3000 B.C. for treating a wide variety of diseases, including coughs, diabetes, hepatic disorders, rheumatism and various types of cancer [1,2,3]. …”

Recent developments in solid lipid nanoparticle and surface-modified solid lipid nanoparticle delivery systems for oral delivery of phyto-bioactive compounds in various chronic diseases

“…Besides the protective effect of these bioactive compounds, their bioavailability through oral delivery system is a great challenge for their potential RA treatment. [86][87][88] …”