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

Abstract

Ambuic acid is an organic acid isolated from the solid culture of , 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 E (PGE) 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.

Mixtures of natural antimicrobials can reduce Campylobacter jejuni, Salmonella enterica and Clostridium perfringens infections and cellular inflammatory response in MDCK cells

“…Thirdly, organic acids (e.g. Ambuic acid) exert anti-inflammatory effects by blocking the ERK signalling pathway [ 41 ]. In this study Auraguard blocked the H 2 O 2 activated ERK signalling pathway, prevented inflammation and averted the damaging effect on tight junction structures.…”

Benzophenone Compounds, from a Marine-Derived Strain of the Fungus Pestalotiopsis neglecta, Inhibit Proliferation of Pancreatic Cancer Cells by Targeting the MEK/ERK Pathway

“…Up to now, a total of seven natural compounds of the class of pestalachloride have been obtained from the genus of Pestalotiopsis . ,,, Pestalachlorides are dichlorinated, highly functionalized benzophenone derivatives with a fused bi-, tri-, or tetracyclic ring and exhibited a variety of biological activities, including antifungal, antifouling, and antibacterial , activities. Although pestalone ,,, and pestalachlorides ,,, have been obtained from a variety of fungi of the genus of Pestalotiopsis , it is the first time to report pestalones and pestalachlorides from a strain of the fungus Pestalotiopsis neglecta , where only a few ambuic acid derivatives were previously reported. , …”

Comparison of nutritional compositions of foxtail millet from the different cultivation regions by UPLC‐Q‐Orbitrap HRMS based metabolomics approach

“…For the characteristic metabolites in the GP millet, 4-guanidinobutyric acid might be useful for the treatment and/or protection of gastritis (Hwang & Jeong, 2012). Ambuic acid showed anti-inflammatory activity and antimicrobial activity against Gram-positive bacterium (Zhang et al, 2018). Trigonelline…”