PMID- 27463712 OWN - NLM STAT- MEDLINE DCOM- 20170321 LR - 20181113 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 17 IP - 8 DP - 2016 Jul 25 TI - Moracin C, A Phenolic Compound Isolated from Artocarpus heterophyllus, Suppresses Lipopolysaccharide-Activated Inflammatory Responses in Murine Raw264.7 Macrophages. LID - 10.3390/ijms17081199 [doi] LID - 1199 AB - Artocarpus heterophyllus, a popular tropical fruit commonly known as the jackfruit tree, is normally planted in subtropical or tropical areas. Since a variety of phytochemicals isolated from A. heterophyllus have been found to possess potently anti-inflammatory, antiviral and antimalarial activities, researchers have devoted much interest to its potential pharmaceutical value. However, the exact mechanism underlying its anti-inflammatory activity is not well characterized. In this study, seven natural products isolated from A. heterophyllus, including 25-Hydroxycycloart-23-en-3-one (HY), Artocarpin (AR), Dadahol A (DA), Morachalcone A (MA), Artoheterophyllin B (AB), Cycloheterophyllin (CY) and Moracin C (MC) were collected. Lipopolysaccharide (LPS)-stimulated inflammatory response in RAW264.7 macrophages were used in this study. Among these compounds, MC significantly inhibited LPS-activated reactive oxygen species (ROS) and nitric oxide (NO) release without marked cytotoxicity. Furthermore, MC effectively reduced LPS stimulated up-regulation of mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and serval pro-inflammatory cytokines (interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha)). Mechanistic studies revealed that the anti-inflammatory effect of MC was associated with the activation of the mitogen activated protein kinases (MAPKs) (including p38, ERK and JNK) and nuclear factor-kappaB (NF-kappaB) pathways, especially reducing the nuclear translocation of NF-kappaB p65 subunit as revealed by nuclear separation experiment and confocal microscopy. FAU - Yao, Xue AU - Yao X AD - Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China. shirleyyao715@gmail.com. FAU - Wu, Dang AU - Wu D AD - Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China. wudang19891013@163.com. FAU - Dong, Ningning AU - Dong N AD - Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China. zoednn@126.com. FAU - Ouyang, Ping AU - Ouyang P AD - Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China. ouyangping2012@yeah.net. FAU - Pu, Jiaqian AU - Pu J AD - Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China. pujiaqian2014@163.com. FAU - Hu, Qian AU - Hu Q AD - Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China. huqian_ECUST@163.com. FAU - Wang, Jingyuan AU - Wang J AD - Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China. joan_wangjy@outlook.com. FAU - Lu, Weiqiang AU - Lu W AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. wqlu@bio.ecnu.edu.cn. FAU - Huang, Jin AU - Huang J AD - Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China. huangjin@ecust.edu.cn. LA - eng PT - Journal Article DEP - 20160725 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Benzofurans) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (RNA, Messenger) RN - 0 (Stilbenes) RN - 0 (moracin C) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Apoptosis/drug effects MH - Artocarpus/*chemistry MH - Benzofurans/*pharmacology MH - Blotting, Western MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Cytokines/genetics/metabolism MH - Fluorescent Antibody Technique MH - HEK293 Cells MH - Humans MH - Inflammation/chemically induced/drug therapy/*immunology/pathology MH - Lipopolysaccharides/*toxicity MH - Macrophages/cytology/drug effects/*immunology MH - Mice MH - RNA, Messenger/genetics MH - Real-Time Polymerase Chain Reaction MH - Reverse Transcriptase Polymerase Chain Reaction MH - Stilbenes/*pharmacology PMC - PMC5000597 OTO - NOTNLM OT - MAPKs OT - Moracin C OT - NF-kappaB OT - inflammation OT - phenols EDAT- 2016/07/28 06:00 MHDA- 2017/03/23 06:00 PMCR- 2016/08/01 CRDT- 2016/07/28 06:00 PHST- 2016/05/04 00:00 [received] PHST- 2016/07/13 00:00 [revised] PHST- 2016/07/18 00:00 [accepted] PHST- 2016/07/28 06:00 [entrez] PHST- 2016/07/28 06:00 [pubmed] PHST- 2017/03/23 06:00 [medline] PHST- 2016/08/01 00:00 [pmc-release] AID - ijms17081199 [pii] AID - ijms-17-01199 [pii] AID - 10.3390/ijms17081199 [doi] PST - epublish SO - Int J Mol Sci. 2016 Jul 25;17(8):1199. doi: 10.3390/ijms17081199.