Anti-inflammatory action of ambuic acid, a natural product isolated from the solid culture of Pestalotiopsis neglecta , through blocking ERK/JNK mitogen-activated protein kinase signaling pathway.

Ambuic acid is an organic acid isolated from the solid culture of Pestalotiopsis neglecta , which is an endophytic fungus that widely exists in many species of plants. Ambuic acid has been reported to exert antimicrobial activity against Gram-positive bacterium. The aim of the present study was to investigate the inhibitory effect of ambuic acid on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages. The results demonstrated that ambuic acid significantly suppressed the overproduction of nitric oxide (NO) and prostaglandin E2 (PGE2 ) in a dose-dependent manner. Furthermore, ambuic acid also inhibited the release of the proinflammatory cytokine interleukin-6 (IL-6) however, no inhibition of the release of tumor necrosis factor-α (TNF-α) was observed. Further investigations indicated that ambuic acid downregulated the LPS-induced high expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins, as well as inhibited the enzymatic activity of iNOS and COX-2. In addition, ambuic acid suppressed the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2) and c-Jun N-terminal kinase (JNK) induced by LPS. However, ambuic acid did not inhibit the phosphorylation of p38 mitogen-activated protein kinase (MAPK), the degradation of IκB-α protein or the nuclear translocation of nuclear transcription factor-κB (NF-κB) p65 subunit. These results suggested that ambuic acid may exert anti-inflammatory action by blocking the activation of the ERK/JNK MAPK signaling pathway, without the involvement of the p38 MAPK or NF-κB signaling pathways.