Curcumin reduces prostaglandin E2, matrix metalloproteinase-3 and proteoglycan release in the secretome of interleukin 1β-treated articular cartilage

Abstract

Objective: Curcumin (diferuloylmethane) is a phytochemical with potent anti-inflammatory and anti-oxidant properties, and has therapeutic potential for the treatment of a range of inflammatory diseases, including osteoarthritis (OA). The aim of this study was to determine whether non-toxic concentrations of curcumin can reduce interleukin-1beta (IL-1β)-stimulated inflammation and catabolism in an explant model of cartilage inflammation. Methods: Articular cartilage explants and primary chondrocytes were obtained from equine metacarpophalangeal joints. Curcumin was added to monolayer cultured primary chondrocytes and cartilage explants in concentrations ranging from 3μM-100μM. Prostaglandin E 2 (PGE 2) and matrix metalloproteinase (MMP)-3 release into the secretome of IL-1β-stimulated explants was measured using a competitive ELISA and western blotting respectively. Proteoglycan (PG) release in the secretome was measured using the 1,9-dimethylmethylene blue (DMMB) assay. Cytotoxicity was assessed with a live/dead assay in monolayer cultures after 24 hours, 48 hours and five days, and in explants after five days. Results: Curcumin induced chondrocyte death in primary cultures (50μM p<0.001 and 100μM p<0.001) after 24 hours. After 48 hours and five days, curcumin (≥25μM) significantly increased cell death ( p<0.001 both time points). In explants, curcumin toxicity was not observed at concentrations up to and including 25μM after five days. Curcumin (≥3μM) significantly reduced IL-1β-stimulated PG ( p<0.05) and PGE 2 release ( p<0.001) from explants, whilst curcumin (≥12μM) significantly reduced MMP-3 release ( p<0.01). Conclusion: Non-cytotoxic concentrations of curcumin exert anti-catabolic and anti-inflammatory effects in cartilage explants.

Brazilin blocks catabolic processes in human osteoarthritic chondrocytes via inhibition of NFKB1/p50

“…Of note, the concentration of 10 ng/ml IL‐1β and TNF‐α which we used in our study for cartilage explant and chondrocyte treatment was markedly higher than the range of these cytokines reported in the synovial fluid of OA patients, which has been reported to be 1.21 ± 0.01 pg/ml to 6 ± 18 pg/ml for IL‐1β and 3.09 ± 1.38 pg/ml to 4 ± 20 pg/ml for TNF‐α . However, based on our own experimental experience and in line with common approaches in the literature, the applied cytokine concentrations in the present study were deliberately chosen to induce a maximized inflammatory response in vitro …”

Effective Timing of Curcumin Ingestion to Attenuate Eccentric Exercise-Induced Muscle Soreness in Men

“…Meanwhile, in the group that ingested curcumin after the exercise, significant improvements in ROM and attenuation of muscle soreness were observed after 3-4 d of exercise. In the previous study, curcumin had a significant effect in suppressing the production of cyclooxygenase (19), prostaglandin E2 (20), and histamine (21), which are algogenic substances. Furthermore, curcumin is associated with desensitization of nociceptor (reduction of nociceptive response) evaluated electrophysiologically with animal neurons in vitro and inhibition of transient receptor ion channels involved in the generation of painful stimuli such as TRPV1 and TRPA1 (22,23).…”

Decrease of a specific biomarker of collagen degradation in osteoarthritis, Coll2-1, by treatment with highly bioavailable curcumin during an exploratory clinical trial

“…With 2 capsules administered orally, the mean of Cmax on 12 individuals was 0.9 μM, with a statistical extrapolation at 1.6 μM with 4 capsules (84 mg and 168 mg of curcumin respectively) [19]. In vitro, curcumin significantly inhibits pro-inflammatory cytokines and prostanoids, and matrix-metalloproteases by chondrocytes [10,28]. Moreover, it is also able to promote chondrogenesis [29] and to block tumor necrosis factor (TNF) action and production both in vitro and in vivo [30].…”