PMID- 30116402 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220330 IS - 1792-0981 (Print) IS - 1792-1015 (Electronic) IS - 1792-0981 (Linking) VI - 16 IP - 2 DP - 2018 Aug TI - 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. PG - 1538-1546 LID - 10.3892/etm.2018.6294 [doi] AB - 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 E(2) (PGE(2)) 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-alpha (TNF-alpha) 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 IkappaB-alpha protein or the nuclear translocation of nuclear transcription factor-kappaB (NF-kappaB) 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-kappaB signaling pathways. FAU - Zhang, Qian AU - Zhang Q AD - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong 264003, P.R. China. FAU - Luan, Ruiling AU - Luan R AD - Pharmacy Dispensing Center, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China. FAU - Li, Huixiang AU - Li H AD - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong 264003, P.R. China. FAU - Liu, Yanan AU - Liu Y AD - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong 264003, P.R. China. FAU - Liu, Pan AU - Liu P AD - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong 264003, P.R. China. FAU - Wang, Liying AU - Wang L AD - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong 264003, P.R. China. FAU - Li, Danna AU - Li D AD - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong 264003, P.R. China. FAU - Wang, Mengdi AU - Wang M AD - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong 264003, P.R. China. FAU - Zou, Qiang AU - Zou Q AD - Yantai Branch of Shandong Technology Transfer Center, Chinese Academy of Sciences, Yantai, Shandong 264003, P.R. China. FAU - Liu, Hongwei AU - Liu H AD - State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, P.R. China. FAU - Matsuzaki, Keiichi AU - Matsuzaki K AD - School of Pharmacy, Nihon University, Funabashi, Chiba 274-8555, Japan. FAU - Zhao, Feng AU - Zhao F AD - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong 264003, P.R. China. LA - eng PT - Journal Article DEP - 20180612 PL - Greece TA - Exp Ther Med JT - Experimental and therapeutic medicine JID - 101531947 PMC - PMC6090306 OTO - NOTNLM OT - Anti-inflammatory activity OT - Pestalotiopsis neglecta OT - ambuic acid OT - cyclooxygenase-2 OT - inducible nitric oxide synthase OT - mitogen-activated protein kinase EDAT- 2018/08/18 06:00 MHDA- 2018/08/18 06:01 PMCR- 2018/06/12 CRDT- 2018/08/18 06:00 PHST- 2017/03/08 00:00 [received] PHST- 2018/04/24 00:00 [accepted] PHST- 2018/08/18 06:00 [entrez] PHST- 2018/08/18 06:00 [pubmed] PHST- 2018/08/18 06:01 [medline] PHST- 2018/06/12 00:00 [pmc-release] AID - ETM-0-0-6294 [pii] AID - 10.3892/etm.2018.6294 [doi] PST - ppublish SO - Exp Ther Med. 2018 Aug;16(2):1538-1546. doi: 10.3892/etm.2018.6294. Epub 2018 Jun 12.