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

Abstract

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-1 beta 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.