TAK1 in the AP-1 pathway is a critical target of Saururus chinensis (Lour.) Baill in its anti-inflammatory action.

ETHNOPHARMACOLOGICAL RELEVANCE: Saururus chinensis (Lour.) Baill (Saururaceae), also known as Asian lizard's tail, is a plant commonly found in East Asia. Its leaves have been used in traditional medicine to treat many diseases such as edema, pneumonia, hypertension, leproma, jaundice, gonorrhea, and rheumatoid arthritis. AIM OF THE STUDY: Based on the efficacies of S. chinensis, the anti-inflammatory effects of this plant and the molecular mechanism were evaluated using the ethanol extract of S. chinensis leaves (Sc-EE). MATERIALS AND METHODS: The production of pro-inflammatory mediators and cytokines in response to Sc-EE was evaluated using Griess and semi-quantitative reverse transcription-polymerase chain reactions. Furthermore, relevant proteins including c-Jun, c-Fos, p38, JNK, ERK, MEK1/2, MKK3/6, MKK4/7, and TAK1 were detected through immunoblotting. RESULTS: Sc-EE diminished production of nitric oxide (NO); decreased expression levels of cyclooxygenase (COX)-2, interleukin (IL)-6, inducible NO synthase (iNOS), and IL-1ß in LPS-stimulated RAW264.7 cells; and attenuated activator protein 1 (AP-1)-mediated luciferase activities. The extract markedly downregulated the phosphorylation of TAK1, upregulated thermal stability of TAK1, and reduced TAK1/AP-1-mediated luciferase activity in LPS-treated RAW264.7 cells and TAK1-overexpressing HEK293T cells. CONCLUSIONS: These results demonstrated that Sc-EE suppresses pro-inflammatory gene expression through blockade of the TAK1/AP-1 pathway in LPS-treated RAW264.7 macrophages, implying that inhibition of TAK1/AP-1 signaling by S. chinensis is a key event in its anti-inflammatory activity.

Fisetin inhibits matrix metalloproteinases and reduces tumor cell invasiveness and endothelial cell tube formation.

Matrix metalloproteinases (MMPs) play an important role in tissue remodeling during normal physiological situations and pathological implications such as tumor invasion and metastasis. MMP inhibitors were screened from extracts of medicinal herbs by an enzymatic assay using the MMP-14 catalytic domain. Among samples tested, a methanol extract of the root of Dalbergia odorifera T. CHEN (Leguminosae) showed the strongest inhibitory activity. The inhibitory component was purified through fractionation methods and identified as fisetin, abundant in many fruits and vegetables. In addition to inhibition of MMP-14, fisetin inhibits MMP-1, MMP-3, MMP-7, and MMP-9, more efficiently than a naturally occurring MMP inhibitor tetracycline. Fisetin dose-dependently inhibits proliferation of fibrosarcoma HT-1080 cells and human umbilical vascular endothelial cells (HUVECs), MMP-14-mediated activation of proMMP-2 in HT-1080 cells, invasiveness of HT-1080 cells, and in vitro tube formation of HUVECs. Therefore, fisetin could be valuable as a chemopreventive agent against cancer and a lead compound for development of therapeutic MMP inhibitors.