Benefit of combining curcumin, harpagophytum and bromelain to reduce inflammation in osteoarthritic synovial cells

Abstract

Background: Osteoarthritis is the most common cause of arthritis affecting millions of people worldwide, characterized by joint pain and in ammation. It is a complex disease involving in ammatory factors and affecting the whole joint including synovium. Since drug combination is widely used to treat chronic in ammatory diseases, a similar strategy may be worth of interest to design plant-derived natural products to reduce in ammation in OA joint. Here, we characterized the response of OA synovial cells to lipopolysaccharide (LPS) and investigated the biological action of the combination of curcumin, harpagophytum and bromelain in this original in vitro model of osteoarthritis.Methods: Primary, human synovial cells from OA patients were stimulated with LPS and proteomic analysis was performed. Bioinformatics analysis were performed using Cytoscape App and SkeletalVis databases. Additionally, cells were treated with curcumin, harpagophytum and bromelain alone or the three vegetal compounds together. The expression of genes involved in in ammation, pain or catabolism were determined by RT-PCR. The release of the encoded proteins by these genes and of prostaglandin E2 (PGE2) were also assayed by ELISA.Results: Proteomic analysis demonstrated that LPS induces the expression of numerous proteins involved in OA process in human OA synovial cells. In particular, it stimulates in ammation through the production of pro-in ammatory cytokines (Interleukin-6, IL-6), the catabolism through an increase of metalloproteases (MMP-1, MMP-3, MMP-13), and the production of pain-mediating neurotrophin (Nerve Growth Factor, NGF). These increases were observed at level of mRNA levels and of protein release. LPS also increases the amount of PGE2, another in ammation and pain mediator. At doses tested, vegetal extracts had little effects: only curcumin slightly counteracted the effects of LPS on NGF and MMP13 mRNA, and PGE2, IL-6 and MMP13 release. In contrast the association of curcumin with harpagophytum and bromelain reversed lots of effects of LPS in human OA synovial cells. It signi cantly reduced the gene expression and/or the release of proteins involved in catabolism (MMP3 and 13), in ammation (IL-6) and pain (PGE2 and NGF). Conclusion:We show that the stimulation of human OA synovial cells with LPS permit to induce protein changes similar to an in amed OA synovial tissues. In addition, using this model, we demonstrate that the combination of three vegetal compounds, namely curcumin, harpagophytum and bromelain have anti-in ammatory and anti-catabolic action in synovial cells and may thus reduce OA progression and related-pain.

Anticancer properties of bromelain: State-of-the-art and recent trends

“…The combination of curcumin, harpagophytum and bromelain has been shown to reduce inflammation and pain in osteoarthritic human synovial cells, through the decrease of prostaglandin E2, Nerve Growth Factor (NGF), IL-6 ( 148 ). Similarly to the previous study, the combination treatment of bromelain, trypsin, and rutin resulted in a significant reduction in pain and inflammation in 103 patients with osteoarthritis of the knee ( 149 ).…”