Ginsenoside Rg3 regulates S-nitrosylation of the NLRP3 inflammasome via suppression of iNOS

Yoon, Sung-Jin; Park, Jun-Young; Choi, Song; Lee, Jin-Bong; Jung, Haiyoung; Kim, Tae-Don; Yoon, Suk Ran; Choi, Inpyo; Shim, Sungbo; Park, Young-Jun

doi:10.1016/J.BBRC.2015.06.080

Title: Ginsenoside Rg3 regulates S-nitrosylation of the NLRP3 inflammasome via suppression of iNOS

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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. - Highlights: • Ginsenosides Rg3 inhibits NO production through the regulation of iNOS expression. • Ginsenosides Rg3 inhibits the S-nitrosylation of the NLRP3 inflammasome. • Ginsenosides Rg3more »« less

Authors:

Yoon, Sung-Jin; Park, Jun-Young ^[1]; Choi, Song ^[1]; Lee, Jin-Bong; Jung, Haiyoung; Kim, Tae-Don; Yoon, Suk Ran; Choi, Inpyo ^[1]; Shim, Sungbo ^[2]; Park, Young-Jun ^[1]

Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon (Korea, Republic of)
Department of Biomedical Sciences & Neuromarker Resource Bank (NRB), University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of)

Publication Date:: Fri Aug 07 00:00:00 EDT 2015

OSTI Identifier:: 22462167

Resource Type:: Journal Article

Journal Name:: Biochemical and Biophysical Research Communications

Additional Journal Information:: Journal Volume: 463; Journal Issue: 4; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X

Country of Publication:: United States

Language:: English

Subject:: 60 APPLIED LIFE SCIENCES; APOPTOSIS; DISEASES; INFLAMMATION; INHIBITION; IRRADIATION; MACROPHAGES; MICE; NITRIC OXIDE; OXIDATION; OXYGEN; SPLEEN CELLS; STRESSES; SURVIVAL TIME

Citation Formats


                    Yoon, Sung-Jin, Park, Jun-Young, Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon, Choi, Song, Lee, Jin-Bong, Jung, Haiyoung, Kim, Tae-Don, Yoon, Suk Ran, Choi, Inpyo, Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon, Shim, Sungbo, Park, Young-Jun, and Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon. Ginsenoside Rg3 regulates S-nitrosylation of the NLRP3 inflammasome via suppression of iNOS.  United States: N. p., 2015. 
        Web.  doi:10.1016/J.BBRC.2015.06.080.

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                    Yoon, Sung-Jin, Park, Jun-Young, Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon, Choi, Song, Lee, Jin-Bong, Jung, Haiyoung, Kim, Tae-Don, Yoon, Suk Ran, Choi, Inpyo, Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon, Shim, Sungbo, Park, Young-Jun, & Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon. Ginsenoside Rg3 regulates S-nitrosylation of the NLRP3 inflammasome via suppression of iNOS.  United States.  https://doi.org/10.1016/J.BBRC.2015.06.080

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                    Yoon, Sung-Jin, Park, Jun-Young, Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon, Choi, Song, Lee, Jin-Bong, Jung, Haiyoung, Kim, Tae-Don, Yoon, Suk Ran, Choi, Inpyo, Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon, Shim, Sungbo, Park, Young-Jun, and Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon. 2015.  
        "Ginsenoside Rg3 regulates S-nitrosylation of the NLRP3 inflammasome via suppression of iNOS".  United States.  https://doi.org/10.1016/J.BBRC.2015.06.080.

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@article{osti_22462167,

  title        = {Ginsenoside Rg3 regulates S-nitrosylation of the NLRP3 inflammasome via suppression of iNOS},

  author       = {Yoon, Sung-Jin and Park, Jun-Young and Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon and Choi, Song and Lee, Jin-Bong and Jung, Haiyoung and Kim, Tae-Don and Yoon, Suk Ran and Choi, Inpyo and Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon and Shim, Sungbo and Park, Young-Jun and Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon},

  abstractNote = {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. - Highlights: • Ginsenosides Rg3 inhibits NO production through the regulation of iNOS expression. • Ginsenosides Rg3 inhibits the S-nitrosylation of the NLRP3 inflammasome. • Ginsenosides Rg3 suppress on the LPS- or UV-irradiation-induced ROS levels in cells.},

  doi          = {10.1016/J.BBRC.2015.06.080},

  url          = {https://www.osti.gov/biblio/22462167},
  journal      = {Biochemical and Biophysical Research Communications},

  issn         = {0006-291X},

  number       = 4,

  volume       = 463,

  place        = {United States},

  year         = {Fri Aug 07 00:00:00 EDT 2015},

  month        = {Fri Aug 07 00:00:00 EDT 2015}

}

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