Compounds DRG and DAG, Two Phenol Glycosides, Inhibit TNF-α-stimulated Inflammatory Response through Blocking NF-kB/AKT/JNK Signaling Pathways in MH7A Cells

Fourteen constituents were recently isolated from the roots of Dendropanax dentiger with cyclooxygenase-2 (COX-2) inhibitory effects. However, the effect of 14 constituents on rheumatoid arthritis (RA) and their action mechanism remain unclear. The study aimed to explore the anti-RA effect and potential mechanism of these constituents in tumor necrosis factor alpha (TNF-alpha)-stimulated human RA fibroblast-like synoviocytes (MH7A cells). The cell viability, nitric oxide (NO) production, inflammatory cytokine levels, and protein expressions were measured by cell counting kit-8 (CCK-8), Griess reagent, ELISA, and Western blot assays, respectively. Results showed that 14 constituents (40 mu M) have no cytotoxicity for MH7A cells. Among them, two phenols including 3,4-dimethoxyphenyl-1-O-alpha-l-rhamnopyranosyl-(1 -> 6)-O-beta-d-glucopyranoside (DRG) and 3,4-dimethoxyphenol-beta-d-apiofuranosyl-(1 -> 6)-beta-d-glucopyranoside (DAG) were shown to significantly inhibit the NO production with IC50 values of 5.25 +/- 0.34 and 5.35 +/- 0.31 mu M, respectively. They also remarkably decreased the release of interleukin (IL)-2, 6, 8, and interferon (IFN)-gamma, as well as prominently reduced the phosphorylation protein levels of p65, IkB alpha, AKT, and JNK at a concentration of 10 mu M. Taken together, DRG and DAG could inhibit TNF-alpha-induced inflammatory response through blocking NF-kB/AKT/JNK signaling pathways in MH7A cells, thus could be promising against RA and other inflammation-related agents.