Evaluation of MMP Inhibitors Isolated from Ligustrum japonicum Fructus

Abstract

The current study investigated the ability of two secoiridoids, GL-3 (1) and oleonuezhenide (2), isolated from the fruits of Ligustrum japonicum to inhibit MMP-2 and -9 activity in phorbol 12-myristate 13-acetate (PMA)-induced HT-1080 human fibrosarcoma cells. Both compounds 1 and 2 were able to exert lowered gelatin digestion activity for MMP-2 and -9 tested by gelatin zymography via suppressing the release of MMPs to culture medium according to ELISA results. Treatment with compounds was also able to suppress the expression of both mRNA and protein levels of MMP-2 and -9. Action mechanism behind the MMP inhibitory effect of the compounds was suggested to be via MAPK pathway indicated by decreased levels of phosphorylated p38, ERK and JNK proteins evaluated employing immunoblotting. Compound 1 was shown to be slightly more active to inhibit MMP-2 and -9, however, compound 2 showed more regular dose-dependency during inhibition. In conclusion, this study suggested that GL-3 and oleonuezhenide were notable natural origin potent MMP inhibitors and could serve as lead compounds for development of anti-invasive MMP inhibitors against tumor metastasis.

Salidroside, 8(E)-Nuezhenide, and Ligustroside from Ligustrum japonicum Fructus Inhibit Expressions of MMP-2 and -9 in HT 1080 Fibrosarcoma

“…In the course of screening inhibitors for MMP-2 and MMP-9 from natural resources, we found that an extract of Ligustrum japonicum fructus had an MMP inhibitory effect, and we recently reported that two compounds (GL-3 and oleonuezhenide) isolated from it significantly inhibited MMP-2 and MMP-9 [ 16 , 17 ]. In addition to GL-3 and oleonuezhenide, 1 H NMR spectral analysis of the chromatographic fractions of the above plant extract showed that structurally related substances were present as minor components in the more polar fraction.…”