PMID- 30867482 OWN - NLM STAT- MEDLINE DCOM- 20201020 LR - 20210109 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 9 IP - 1 DP - 2019 Mar 13 TI - Rg6, a rare ginsenoside, inhibits systemic inflammation through the induction of interleukin-10 and microRNA-146a. PG - 4342 LID - 10.1038/s41598-019-40690-8 [doi] LID - 4342 AB - The immunobiological functions of Rg6, a rare ginsenoside from ginseng, have been largely unreported. In this paper, we demonstrate that Rg6 has a significant immunosuppressive function on Toll-like receptor (TLR) 4-induced systemic inflammatory responses. Rg6 was found to negatively regulate pro-inflammatory responses and severity in vivo, and thus induced recovery in mice with lipopolysaccharide (LPS)-induced septic shock and cecal ligation and puncture (CLP)-induced sepsis. Rg6 treatment also facilitated recovery in mice with LPS-induced lung damage via reduced neutrophil infiltration and tumor necrosis factor-alpha expression in lung tissues. Rg6 injection also downregulated pro-inflammatory cytokines and increased the levels of interleukin (IL)-10 in the serum of septic mice. Mechanistically, Rg6 did not induce TLR negative regulators, such as A20 and IRAK-M, in bone marrow-derived macrophages (BMDMs). Instead, addition of Rg6 to LPS-activated BMDMs augmented IL-10 expression, whereas it inhibited inflammatory signaling, such as by nuclear factor kappaB activation and mitogen-activated protein kinases. Furthermore, Rg6 significantly induced miR-146a, an operator miRNA for anti-inflammation, in BMDMs. Collectively, these data indicate that Rg6 inhibits inflammatory responses through the induction of IL-10 and miR-146a. FAU - Paik, Seungwha AU - Paik S AD - Department of Microbiology, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea. AD - Department of Medical Science, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea. AD - Infection Control Convergence Research Center, Chungnam National University, Daejeon, 35015, Republic of Korea. FAU - Choe, Jin Ho AU - Choe JH AD - Department of Microbiology, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea. AD - Department of Medical Science, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea. AD - Infection Control Convergence Research Center, Chungnam National University, Daejeon, 35015, Republic of Korea. FAU - Choi, Ga-Eun AU - Choi GE AD - Infection Control Convergence Research Center, Chungnam National University, Daejeon, 35015, Republic of Korea. AD - College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea. FAU - Kim, Ji-Eun AU - Kim JE AD - Infection Control Convergence Research Center, Chungnam National University, Daejeon, 35015, Republic of Korea. AD - College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea. FAU - Kim, Jin-Man AU - Kim JM AD - Department of Medical Science, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea. AD - Infection Control Convergence Research Center, Chungnam National University, Daejeon, 35015, Republic of Korea. AD - Department of Pathology, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea. FAU - Song, Gyu Yong AU - Song GY AD - Infection Control Convergence Research Center, Chungnam National University, Daejeon, 35015, Republic of Korea. gysong@cnu.ac.kr. AD - College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea. gysong@cnu.ac.kr. FAU - Jo, Eun-Kyeong AU - Jo EK AD - Department of Microbiology, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea. hayoungj@cnu.ac.kr. AD - Department of Medical Science, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea. hayoungj@cnu.ac.kr. AD - Infection Control Convergence Research Center, Chungnam National University, Daejeon, 35015, Republic of Korea. hayoungj@cnu.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190313 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Ginsenosides) RN - 0 (IL10 protein, mouse) RN - 0 (Lipopolysaccharides) RN - 0 (MicroRNAs) RN - 0 (Mirn146 microRNA, mouse) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Animals MH - Ginsenosides/*pharmacology MH - Inflammation/*prevention & control MH - Interleukin-10/*biosynthesis MH - Lipopolysaccharides/toxicity MH - Macrophages/metabolism MH - Mice MH - MicroRNAs/*biosynthesis MH - Sepsis/chemically induced/etiology/metabolism/prevention & control MH - Survival Rate PMC - PMC6416268 COIS- The authors declare no competing interests. EDAT- 2019/03/15 06:00 MHDA- 2020/10/21 06:00 PMCR- 2019/03/13 CRDT- 2019/03/15 06:00 PHST- 2018/10/12 00:00 [received] PHST- 2019/02/15 00:00 [accepted] PHST- 2019/03/15 06:00 [entrez] PHST- 2019/03/15 06:00 [pubmed] PHST- 2020/10/21 06:00 [medline] PHST- 2019/03/13 00:00 [pmc-release] AID - 10.1038/s41598-019-40690-8 [pii] AID - 40690 [pii] AID - 10.1038/s41598-019-40690-8 [doi] PST - epublish SO - Sci Rep. 2019 Mar 13;9(1):4342. doi: 10.1038/s41598-019-40690-8.