title: Ginsenoside Rg3 regulates S-nitrosylation of the NLRP3 inflammasome via suppression of iNOS.
abstract: Ginsenoside Rg3, a specific biological effector, is well-known as a major bioactive ingredient of Panax ginseng. However, its role in the inflammasome activation process remains unclear. In this report, we demonstrate that ginsenosides 20(R)-Rg3 and 20(S)-Rg3 are capable of suppressing both lethal endotoxic shock and the S-nitrosylation of the NLRP3 inflammasome by inhibiting nitric oxide (NO) production through the regulation of inducible nitric oxide synthase (iNOS) expression. In response to lipopolysaccharide (LPS), the reducing effect of 20(S)-Rg3 and 20(R)-Rg3 on nitric oxide led to an increase in the survival time of mice after lethal endotoxin-induced shock, and excess levels of NO inhibited IL-1β production via the S-nitrosylation of the NLRP3 inflammasome. In addition, ginsenosides 20(R)-Rg3 and 20(S)-Rg3 had suppressive effects on the LPS- or UV-irradiation-induced reactive oxygen species (ROS) levels in macrophage and HaCaT cells and thereby prevented apoptosis of spleen cells in mice. Altogether, these results demonstrate that ginsenoside 20(R)-Rg3 and 20(S)-Rg3, a naturally occurring compound, might act as a dual therapeutic regulator for the treatment of inflammatory and oxidative stress-related diseases.
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, Republic of Korea; Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon, Republic of Korea.
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Yoon
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, Republic of Korea; Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon, Republic of Korea.
authors.forename: Jun-Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, Republic of Korea.
authors.forename: Song
authors.initials: S
authors.lastname: Choi
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, Republic of Korea; Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon, Republic of Korea.
authors.forename: Jin-Bong
authors.initials: JB
authors.lastname: Lee
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, Republic of Korea; Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon, Republic of Korea.
authors.forename: Haiyoung
authors.initials: H
authors.lastname: Jung
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, Republic of Korea; Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon, Republic of Korea.
authors.forename: Tae-Don
authors.initials: TD
authors.lastname: Kim
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, Republic of Korea; Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon, Republic of Korea.
authors.forename: Suk Ran
authors.initials: SR
authors.lastname: Yoon
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, Republic of Korea; Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon, Republic of Korea.
authors.forename: Inpyo
authors.initials: I
authors.lastname: Choi
authors.affiliation: Department of Biomedical Sciences & Neuromarker Resource Bank (NRB), University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea. Electronic address: sungbo@ulsan.ac.kr.
authors.forename: Sungbo
authors.initials: S
authors.lastname: Shim
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, Republic of Korea; Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon, Republic of Korea. Electronic address: pyj71@kribb.re.kr.
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Park
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D036145:Ginsenosides / Q000494:pharmacology*; D058847:Inflammasomes / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012772:Shock, Septic / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D002352:Carrier Proteins; D036145:Ginsenosides; D058847:Inflammasomes; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D017382:Reactive Oxygen Species; C097367:ginsenoside Rg3; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II
keywords: Ginsenoside Rg3; NLRP3 inflammasome; NO; S-nitrosylation; iNOS