Scientific evidence and rationale for the development of curcumin and resveratrol as nutraceutricals for joint health

Abstract

Interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) are key cytokines that drive the production of inflammatory mediators and matrix-degrading enzymes in osteoarthritis (OA). These proinflammatory cytokines bind to their respective cell surface receptors and activate inflammatory signaling pathways culminating with the activation of nuclear factor κB (NF-κB), a transcription factor that can be triggered by a host of stress-related stimuli including, excessive mechanical stress and ECM degradation products. Once activated, NF-κB regulates the expression of many cytokines, chemokines, adhesion molecules, inflammatory mediators, and several matrix-degrading enzymes. Therefore, proinflammatory cytokines, their cell surface receptors, NF-κB and downstream signaling pathways are therapeutic targets in OA. This paper critically reviews the recent literature and outlines the potential prophylactic properties of plant-derived phytochemicals such as curcumin and resveratrol for targeting NF-κB signaling and inflammation in OA to determine whether these phytochemicals can be used as functional foods.

Keywords: OA; RA; articular cartilage; curcumin; functional food; osteoarthritis; phytochemical; resveratrol; rheumatoid arthritis.

Figures

Figure 1

Structure of human articular cartilage. This figure illustrates a sample of human cartilage from a tissue microarray developed by the Cooperative Human Tissue Network (CHTN) [22] of the National Cancer Institute [23]. Cartilage is predominantly an avascular, aneural and alymphatic load-bearing connective tissue consisting of a single cell type known as the chondrocyte. Blood vessels are only present in subchondral bone.

Figure 2

Molecular composition of the ECM of articular cartilage. The major collagenous and non-collagenous components of the territorial and interterritorial cartilage ECM are illustrated.

Figure 3

Summary of the major molecular and cellular changes that occur in the synovial joint during inflammation in OA. Summary of the major synovial, chondral and subchondral changes observed in OA. This schematic also highlights the actions of various white blood cells and inflammatory mediators in OA. Chondral changes include cartilage fragmentation (fibrillation), cartilage degradation and loss of collagen type II and glycosaminoglycans, chondrocyte apoptosis (hypocellularity) and matrix mineralization. Synovial membrane changes in OA include inflammation, synovial hypertrophy, recruitment and activation of T cells, macrophages and fibroblasts, production of matrix metalloproteinases (MMPs) and reactive oxygen species (ROS). Synovial fluid alterations in OA include accumulation of MMPs and ROS, release of IL-1β, TNF-α and other proinflammatory cytokines (IL-6, IL-8), release of inflammatory pain mediators such as prostaglandin E2 (PGE2), formation of degradative products and microcrystals. Subchondral alterations in OA include subchondral sclerosis (i.e., eburnation), osteoblast mediated subchondral bone formation, proteolysis (degradation) of IGF-I and IGF-I binding proteins, increased production of some growth factors and cytokines including: transforming growth factor β, TGF-β, PGE2; interleukin 6, IL-6 and IGF-I.

Figure 4

Schematic of the effects of curcumin on the TNF-α receptor and its downstream signaling pathway. The biochemical pathway illustrated here was generated by text mining and makes use of a collection of canonical Ariadne pathways in addition to MedScan text mining.