Inhibitory effects of di-O-demethylcurcumin on interleukin-1β-induced interleukin-6 production from human gingival fibroblasts

Abstract

Background/purpose: Curcumin is a polyphenolic phytochemical isolated from the medicinal plant Curcuma longa L. This phytochemical exhibits anti-inflammatory and antioxidant properties. The aim of this study was to find a curcuminoid compound that has a better effect on the suppression of interleukin-1β (IL-1β)-induced IL-6 production than curcumin in human gingival fibroblasts (HGFs). Materials and methods: The parent curcuminoids 1–3 were isolated from the rhizomes of C. longa and 17 curcuminoid analogs 4–20 were synthesized from the parent curcuminoids. The condition for IL-6 production by HGFs after inducing the cells with IL-1β was optimized. HGFs were incubated with curcuminoids (0.016–20 μg/mL) for 30 minutes before adding IL-1β (2 ng/mL). After 24 hours of incubation, the culture media were harvested and determined for IL-6 contents using an enzyme-linked immunosorbent assay method. Prednisolone, an immunosuppressive drug, was used as a positive control. Half maximal effective concentration (EC50) is measured and reported as the concentration required for 50% inhibition of the levels found in the control medium. Results: The maximum IL-6 production was achieved when the HGFs were exposed to an IL-1β concentration of 2 ng/mL for 24 hours; however, addition of the immunosuppressant prednisolone inhibited the production of IL-6. Among the analogs, di-O-demethylcurcumin (5) exhibited the most potent anti-IL-6 activity with an EC50 of 2.18 ± 0.07 μg/mL, which was approximately eightfold more active than the natural curcuminoids 1–3. Cell viability was not significantly affected when the concentration of di-O-demethylcurcumin was less than 20 μg/mL. Conclusion: Di-O-demethylcurcumin exhibited an inhibitory effect on the production of IL-6 by IL-1β-induced HGFs and can thus serve as a lead compound with its inhibiting property for IL-6 production.

Keywords

• anti-inflammation
• curcumin
• gingival fibroblasts
• interleukin-1β
• interleukin-6