PMID- 30976167 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220408 IS - 1226-8453 (Print) IS - 2093-4947 (Electronic) IS - 1226-8453 (Linking) VI - 43 IP - 2 DP - 2019 Apr TI - Nonsaponin fraction of Korean Red Ginseng attenuates cytokine production via inhibition of TLR4 expression. PG - 291-299 LID - 10.1016/j.jgr.2018.03.003 [doi] AB - BACKGROUND: Ginsenosides of Korean Red Ginseng extracts (RGE) and its saponin components suppress secretion of inflammasome-mediating cytokines, whereas the nonsaponin fraction (NS) of RGE oppositely stimulates cytokine secretion. Although direct exposure of NS to macrophages in mice induces cytokine production, oral administration of NS has not been studied in inflammasome-related disease in animal models. METHODS: Mice were fed RGE or NS for 7 days and then developed peritonitis. Peritoneal cytokines were measured, and peritoneal exudate cells (PECs) were collected to assay expression levels of a set of toll-like receptors (TLRs) and cytokines in response to NS ingestion. In addition, the role of intestinal bacteria in NS-fed mice was assessed. The effect of preexposure to NS in bone marrow-derived macrophages (BMDMs) on cytokine production was further confirmed. RESULTS: NS ingestion attenuated secretion of peritoneal cytokines resulting from peritonitis. In addition, the isolated PECs from NS-fed mice presented lower TLR transcription levels than PECs from control diet-fed mice. BMDMs treated with NS showed downregulation of TLR4 mRNA and protein expression, which was mediated by the TLR4-MyD88-NFkappaB signal pathway. BMDMs pretreated with NS produced less cytokines in response to TLR4 ligands. CONCLUSION: NS administration directly inhibits TLR4 expression in inflammatory cells such as macrophages, thereby reducing secretion of cytokines during peritonitis. FAU - Ahn, Huijeong AU - Ahn H AD - College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Republic of Korea. FAU - Han, Byung-Cheol AU - Han BC AD - College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Republic of Korea. AD - Korea Ginseng Research Institute, Korea Ginseng Corporation, Daejeon, Republic of Korea. FAU - Kim, Jeongeun AU - Kim J AD - College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Republic of Korea. FAU - Kang, Seung Goo AU - Kang SG AD - Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon, Republic of Korea. FAU - Kim, Pyeung-Hyeun AU - Kim PH AD - Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon, Republic of Korea. FAU - Jang, Kyoung Hwa AU - Jang KH AD - Korea Ginseng Research Institute, Korea Ginseng Corporation, Daejeon, Republic of Korea. FAU - So, Seung Ho AU - So SH AD - Korea Ginseng Research Institute, Korea Ginseng Corporation, Daejeon, Republic of Korea. FAU - Lee, Seung-Ho AU - Lee SH AD - Korea Ginseng Research Institute, Korea Ginseng Corporation, Daejeon, Republic of Korea. FAU - Lee, Geun-Shik AU - Lee GS AD - College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Republic of Korea. LA - eng PT - Journal Article DEP - 20180404 PL - Korea (South) TA - J Ginseng Res JT - Journal of ginseng research JID - 100890690 PMC - PMC6437451 OTO - NOTNLM OT - Alum, aluminum potassium sulfate OT - BMDMs, bone marrow-derived macrophages OT - Cytokine OT - HKST, heat-killed Salmonella typhimurium OT - IL, interleukin OT - Korean Red Ginseng extracts OT - LB, Luria-Bertani OT - LCCM, L929 cell-conditioned medium OT - LPS, lipopolysaccharide OT - Lys, lysate OT - MSU, monosodium urate crystal OT - NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells OT - NLRP3, (NOD)2-like receptor protein 3 OT - NOD, nucleotide-binding and oligomerization domain OT - NS, nonsaponin fraction OT - Non, nontreatment OT - Nonsaponin fraction OT - PECs, peritoneal exudate cells OT - Peritonitis OT - RGE, Korean Red Ginseng extracts OT - SF, saponin fraction OT - Sup, supernatant OT - TLR4 OT - TLRs, toll-like receptors OT - ip, intraperitoneally EDAT- 2019/04/13 06:00 MHDA- 2019/04/13 06:01 PMCR- 2018/04/04 CRDT- 2019/04/13 06:00 PHST- 2017/10/19 00:00 [received] PHST- 2018/03/22 00:00 [revised] PHST- 2018/03/26 00:00 [accepted] PHST- 2019/04/13 06:00 [entrez] PHST- 2019/04/13 06:00 [pubmed] PHST- 2019/04/13 06:01 [medline] PHST- 2018/04/04 00:00 [pmc-release] AID - S1226-8453(17)30324-X [pii] AID - 10.1016/j.jgr.2018.03.003 [doi] PST - ppublish SO - J Ginseng Res. 2019 Apr;43(2):291-299. doi: 10.1016/j.jgr.2018.03.003. Epub 2018 Apr 4.