Dataset Information

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 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-? (TNF-?) 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 I?B-? protein or the nuclear translocation of nuclear transcription factor-?B (NF-?B) 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-?B signaling pathways.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC6090306 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Zhang Qian Q Luan Ruiling R Li Huixiang H Liu Yanan Y Liu Pan P Wang Liying L Li Danna D Wang Mengdi M Zou Qiang Q Liu Hongwei H Matsuzaki Keiichi K Zhao Feng F

Experimental and therapeutic medicine 20180612 2

Ambuic acid is an organic acid isolated from the solid culture of <i>Pestalotiopsis neglecta</i>, 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 o ...[more]

PMID: 30116402

Similar Datasets

Project description:Anopheles gambiae is the primary mosquito vector of human malaria parasites in sub-Saharan Africa. To date, three innate immune signaling pathways, including the nuclear factor (NF)-kappaB-dependent Toll and immune deficient (IMD) pathways and the Janus kinase/signal transducers and activators of transcription (Jak-STAT) pathway, have been extensively characterized in An. gambiae. However, in addition to NF-kappaB-dependent signaling, three mitogen-activated protein kinase (MAPK) pathways regulated by JNK, ERK and p38 MAPK are critical mediators of innate immunity in other invertebrates and in mammals. Our understanding of the roles of the MAPK signaling cascades in anopheline innate immunity is limited, so identification of the encoded complement of these proteins, their upstream activators, and phosphorylation profiles in response to relevant immune signals was warranted.In this study, we present the orthologs and phylogeny of 17 An. gambiae MAPKs, two of which were previously unknown and two others that were incompletely annotated. We also provide detailed temporal activation profiles for ERK, JNK, and p38 MAPK in An. gambiae cells in vitro to immune signals that are relevant to malaria parasite infection (human insulin, human transforming growth factor-beta1, hydrogen peroxide) and to bacterial lipopolysaccharide. These activation profiles and possible upstream regulatory pathways are interpreted in light of known MAPK signaling cascades.The establishment of a MAPK "road map" based on the most advanced mosquito genome annotation can accelerate our understanding of host-pathogen interactions and broader physiology of An. gambiae and other mosquito species. Further, future efforts to develop predictive models of anopheline cell signaling responses, based on iterative construction and refinement of data-based and literature-based knowledge of the MAP kinase cascades and other networked pathways will facilitate identification of the "master signaling regulators" in biomedically important mosquito species.

Project description:Fungal endophytes are friendly microorganisms that colonize plants and are important in the interactions between plants and their environment. They generate valuable secondary metabolites that are valuable to both plants and humans. Endophytic fungi with bioactivities were isolated from the leaves of the medicinal plant Ziziphus spina-christi. An efficient isolate was selected and identified as Pestalotiopsis neglecta based on nucleotide sequencing of the internal transcribed spacer region (ITS 1-5.8S-ITS 2) of the 18S rRNA gene (NCBI accession number OP529850); the 564 bp had 99 to 100% similarity with P. neglecta MH860161.1, AY682935.1, KP689121.1, and MG572407.1, according to the BLASTn analysis, following preliminary phytochemical and antifungal screening. The biological activities of this fungus' crude ethyl acetate (EtOAc) extract were assessed. With an efficient radical scavenging activity against 2,2'-diphenyl-1-picrylhydrazyl and an IC50 value of 36.6 µg mL-1, P. neglecta extract has shown its potential as an antioxidant. Moreover, it displayed notable cytotoxic effects against MCF-7 (breast carcinoma, IC50 = 22.4 µg mL-1), HeLa (cervical carcinoma, IC50 = 28.9 µg mL-1) and HepG-2 (liver carcinoma, IC50 = 28.9 µg mL-1). At 10 µg mL-1, EtOAc demonstrated significant DNA protection against hydroxyl radical-induced damage. Based on FT-IR and GC-MS spectral analysis, it was detected that the EtOAc of P. neglecta product contains multiple bioactive functional groups. Subsequently, this validated the features of major different potent compounds; tolycaine, 1H-pyrazol, 1,3,5-trimethyl-, eugenol, 2,5-cyclohexadiene-1,4-dione, 2,6-bis(1,1-dimethyl), and bis(2-ethylhexyl) phthalate. Since these compounds are biologically relevant in various aspects, and distinct biological activities of fungal extract were acceptable in vitro, this suggests that endophytic fungus P. neglecta may be a viable source of bioactive natural products. This could be a good starting point for pharmaceutical applications.

Dataset Information

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.

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets