PMID- 36947736 OWN - NLM STAT- MEDLINE DCOM- 20230406 LR - 20230406 IS - 1520-5118 (Electronic) IS - 0021-8561 (Linking) VI - 71 IP - 13 DP - 2023 Apr 5 TI - Identification of Scoparone from Chinese Olive Fruit as a Modulator of Macrophage Polarization. PG - 5195-5207 LID - 10.1021/acs.jafc.2c08132 [doi] AB - Chinese olive (Canarium album L.) has been highlighted for its remarkable health benefits. We previously showed that the ethyl acetate fraction of Chinese olive (COE) is an effective anti-inflammatory agent. In this study, we used a luciferase-based RAW 264.7 cell platform to detect the transcriptional activity of NF-kappaB, a key mediator of inflammation, and the promoter activity of its downstream target, COX-2. Through functional-oriented screening using these platforms, we further divided COE into several subfractions. Subsequently, we used silica gel column chromatography for purification, and the active compounds were separated and isolated by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). The structure of the resulting compound with high anti-inflammatory activity was then identified as scoparone. Our results showed that scoparone not only inhibited lipopolysaccharide (LPS)-induced secretion of nitric oxide and suppressed M1 macrophage markers (iNOS, Il-6, Ccl2, and Tnf-alpha) but also markedly decreased the production of pro-inflammatory cytokines (IL-6, CCL2, and TNF-alpha). Treatment with scoparone significantly reduced the protein level of TNF-alpha in LPS-treated bone-marrow-derived macrophages (BMDMs). In addition, scoparone promoted macrophages toward an M2 anti-inflammatory phenotype, as determined by the significantly increased gene expression of M2 macrophage markers (Arg1, Ym1, Mrc1, Il-10, and Cd206) and the protein level of Arg1. This study indicates that COE fruit has high therapeutic potential for various inflammatory diseases as a result of switching the macrophage phenotype from pro-inflammatory M1 to anti-inflammatory M2. FAU - Yeh, Yu-Te AU - Yeh YT AUID- ORCID: 0000-0001-7968-6081 AD - Institute of Food Science and Technology, National Taiwan University, Taipei 106, Taiwan. AD - Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, United States. FAU - Hsu, Kuei-Ming AU - Hsu KM AD - Institute of Food Science and Technology, National Taiwan University, Taipei 106, Taiwan. FAU - Chen, Hong-Jhang AU - Chen HJ AUID- ORCID: 0000-0002-9420-0964 AD - Institute of Food Science and Technology, National Taiwan University, Taipei 106, Taiwan. FAU - Su, Nan-Wei AU - Su NW AUID- ORCID: 0000-0002-1402-7349 AD - Laboratory of Food Chemistry, Department of Agricultural Chemistry, National Taiwan University, Taipei 106, Taiwan. FAU - Liao, Yi-Chun AU - Liao YC AD - Department of Biochemical Science and Technology, National Taiwan University, Taipei 106, Taiwan. FAU - Hsieh, Shu-Chen AU - Hsieh SC AD - Institute of Food Science and Technology, National Taiwan University, Taipei 106, Taiwan. LA - eng PT - Journal Article DEP - 20230322 PL - United States TA - J Agric Food Chem JT - Journal of agricultural and food chemistry JID - 0374755 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - H5841PDT4Y (scoparone) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Coumarins) SB - IM MH - Anti-Inflammatory Agents/pharmacology MH - Fruit/chemistry MH - Inflammation/metabolism MH - Interleukin-6/metabolism MH - Lipopolysaccharides/pharmacology MH - *Macrophages/drug effects MH - NF-kappa B/metabolism MH - *Tumor Necrosis Factor-alpha/metabolism MH - Animals MH - Mice MH - RAW 264.7 Cells MH - *Coumarins/pharmacology OTO - NOTNLM OT - Chinese olive OT - inflammation OT - luciferase assay OT - macrophage OT - scoparone EDAT- 2023/03/23 06:00 MHDA- 2023/04/06 06:41 CRDT- 2023/03/22 16:03 PHST- 2023/04/06 06:41 [medline] PHST- 2023/03/23 06:00 [pubmed] PHST- 2023/03/22 16:03 [entrez] AID - 10.1021/acs.jafc.2c08132 [doi] PST - ppublish SO - J Agric Food Chem. 2023 Apr 5;71(13):5195-5207. doi: 10.1021/acs.jafc.2c08132. Epub 2023 Mar 22.