EtOH e tract had no effect and was thus considered to be not suitable for further investigations, the curcuma DMSO e tract as well as the DMSO soluble compound curcumin reduced levels of some disc specific, major proinflammatory cytokines and matri degrading enzymes in our in vitro e periments. We were able to demonstrate that the observed effect was not due to the biologic activity of the solvents DMSO and EtOH, although the anti inflammatory properties of DMSO have most recently been described in human intestinal cells. Specifically, we could demonstrate a reduction in gene e pression of IL 6, MMP1, MMP3 and MMP13 when treating IL 1B prestimulated cells with the curcuma DMSO e tract. Additionally, IL 1B and IL 8 were reduced by cur cumin treatment after 6 hours.

As effects were comparable between the curcuma DMSO e tract and curcumin and as curcumin was detected at high concentrations in the DMSO e tract by HPLC MS, we hypothesize that the major bioactive substance in curcuma DMSO e tracts acting on human intervertebral disc cells could be curcumin. Due to the Entinostat beneficial effects of curcumin, this natural compound may be of benefit for patients with inflammation related back pain, with the potential mode of application being intradiscal injection. Albeit curcumin is whether this effect would also occur on the protein level and in vivo. Therefore, further studies are thus required to demonstrate safety and usefulness of curcumin in human application. So far, only one study investigated the effect of curcumin on human intervertebral disc cells.

This study tested curcumin for its effects on matri protein gene e pression, but not on the e pression of proinflammatory cytokines or matri degrading enzymes. Results of Yu et al. s study indi cated that curcumin is also able to attenuate an IL 1 induced inhibition of SO 9 and collagen II e pression at 20 ug ml, which is higher than the concentra tions used in the present study and which was shown to be a damaging concentration for other cell types. Further more, it has to be noted that both, Yus as well as our study were performed in a 2D culture system, which can cause certain phenotypic changes of disc cells and may thus pos sibly influence cellular behavior to the tested treatment. Pathway analysis Curcumin seems to e hibit its anti inflammatory and anti catabolic effects through versatile mechanisms.

So far, in different cell types, mainly inhibition of NF ��B, MAP kinases and Toll like receptors have been shown to play a role. NF ��B Inhibition of the transcription factor NF ��B is the best described mechanism of action of curcumin in the literature. A recent study in chondrocytes well known for its low bioavailability in case of oral con sumption, in vivo concentrations after injections should not be a limiting factor. The observed gene e pression results are similar to effects that were observed when treating other cell types with curcumin, e. g. leading to a reduction in IL 1B, IL 6, IL 8, MMP1, MMP