Monotropein isolated from the roots of Morinda officinalis ameliorates proinflammatory mediators in RAW 264.7 macrophages and dextran sulfate sodium (DSS)-induced colitis via NF-κB inactivation

We previously demonstrated that monotropein isolated from the roots of Morinda officinalis (Rubiaceae) has anti-inflammatory effects in vivo. In the present study, we investigated the molecular mechanisms underlying the anti-inflammatory effects of monotropein in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and dextran sulfate sodium (DSS)-induced colitis mouse model. Monotropein was found to inhibit the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) mRNA in LPS-induced RAW 264.7 macrophages. Treatment with monotropein decreased the DNA binding activity of nuclear factor-κB (NF-κB). Consistent with these findings, monotropein also suppressed phosphorylation and degradation of inhibitory κB-α (IκB-α), and consequently the translocations of NF-κB. In the DSS-induced colitis model, monotropein reduced disease activity index (DAI), myeloperoxidase (MPO) activity, and inflammation-related protein expressions by suppressing NF-κB activation in colon mucosa. Taken together, these findings suggest that the anti-inflammatory effects of monotropein are mainly related to the inhibition of the expressions of inflammatory mediators via NF-κB inactivation, and support its possible therapeutic role in colitis.

Graphical abstractDownload full-size imageHighlights► Monotropein, an iridoids glycoside, was isolated from the roots of Morinda citrifolia. ► Monotropein inhibited the expressions of iNOS, COX-2, and cytokines in LPS-induced RAW 264.7 macrophages. ► Monotropein inhibited LPS-induced NF-κB activation by suppressing the IKK/IκB-α/NF-κB pathway in RAW 264.7 macrophages. ► Monotropein significantly ameliorated DSS-induced colitis via NF-κB inactivation. ► Monotropein appears to have the potential to prevent inflammatory diseases.