PMID- 30372852 OWN - NLM STAT- MEDLINE DCOM- 20190311 LR - 20190311 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 108 DP - 2018 Dec TI - Red ginseng-derived saponin fraction suppresses the obesity-induced inflammatory responses via Nrf2-HO-1 pathway in adipocyte-macrophage co-culture system. PG - 1507-1516 LID - S0753-3322(18)35266-1 [pii] LID - 10.1016/j.biopha.2018.09.169 [doi] AB - The aim of this study was to investigate the effect of saponin fraction (SF) from red ginseng on obesity-induced inflammatory response in a co-culture system of 3T3-L1 and RAW264.7 cells. HPLC analysis showed that SF contains more than 50% ginsenosides, and Rb1 was the most abundant ginsenoside [135.31 mug/mg (extract)]. The production of nitric oxide and cytokines, induced by adipocyte-conditioned medium (3T3-CM), was significantly decreased by SF. SF (100 mug/mL) suppressed the abundance of tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) by 78%, 40%, and 22%, respectively. This SF-mediated reduction in inflammatory cytokines was due to the suppression of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkappaBalpha) phosphorylation, and translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) into the nucleus. SF also regulated adipokine expression in adipocytes, which were stimulated by macrophage-conditioned medium (RAW-CM); adiponectin expression was upregulated (> 2-fold), while resistin was downregulated (40%). In the contact system of adipocytes and macrophages, SF significantly decreases MCP-1 (37%) and IL-6 (25%) production. In the transwell system, SF (100 mug/mL) significantly increased the abundance of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its target protein, hemoxygenase-1 (HO-1) by 1.5 approximately 3.5-fold and 2.8 approximately 3.6-fold, respectively, thus increasing Nrf2 translocation into nucleus. However, SF-mediated inhibitory effect on the release of IL-6 and MCP-1 cytokines was reversed in the Nrf2 or HO-1 knockdown condition. This result indicated that SF-mediated inhibition of obesity-induced inflammation was dependent on Nrf2 activation. CI - Copyright (c) 2018 Elsevier Masson SAS. All rights reserved. FAU - Kim, Chae Young AU - Kim CY AD - Department of Public Health Sciences, Korea University, Seoul 07249, Republic of Korea. FAU - Kang, Bobin AU - Kang B AD - Department of Public Health Sciences, Korea University, Seoul 07249, Republic of Korea. FAU - Suh, Hyung Joo AU - Suh HJ AD - Department of Public Health Sciences, Korea University, Seoul 07249, Republic of Korea. FAU - Choi, Hyeon-Son AU - Choi HS AD - Department of Food Science and Technology, College of Natural Science, Seoul Women's University, Seoul 139-774, Republic of Korea. Electronic address: hschoi@swu.ac.kr. LA - eng PT - Journal Article DEP - 20181009 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Inflammation Mediators) RN - 0 (Membrane Proteins) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Nfe2l2 protein, mouse) RN - 0 (Saponins) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 1.14.14.18 (Hmox1 protein, mouse) SB - IM MH - 3T3-L1 Cells MH - Adipocytes/drug effects/*metabolism MH - Animals MH - Coculture Techniques MH - Dose-Response Relationship, Drug MH - Heme Oxygenase-1/antagonists & inhibitors/*metabolism MH - Inflammation Mediators/antagonists & inhibitors/metabolism MH - Macrophages/drug effects/*metabolism MH - Membrane Proteins/antagonists & inhibitors/*metabolism MH - Mice MH - NF-E2-Related Factor 2/antagonists & inhibitors/*metabolism MH - Obesity/drug therapy/*metabolism MH - Panax MH - RAW 264.7 Cells MH - Saponins/isolation & purification/pharmacology/*therapeutic use MH - Signal Transduction/drug effects/physiology OTO - NOTNLM OT - Co-culture OT - Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-hemoxygenase-1 (HO-1) signaling pathway OT - Obesity-induced inflammation OT - Saponin fraction EDAT- 2018/10/31 06:00 MHDA- 2019/03/12 06:00 CRDT- 2018/10/31 06:00 PHST- 2018/07/29 00:00 [received] PHST- 2018/09/27 00:00 [revised] PHST- 2018/09/28 00:00 [accepted] PHST- 2018/10/31 06:00 [pubmed] PHST- 2019/03/12 06:00 [medline] PHST- 2018/10/31 06:00 [entrez] AID - S0753-3322(18)35266-1 [pii] AID - 10.1016/j.biopha.2018.09.169 [doi] PST - ppublish SO - Biomed Pharmacother. 2018 Dec;108:1507-1516. doi: 10.1016/j.biopha.2018.09.169. Epub 2018 Oct 9.