PMID- 31475012
OWN - NLM
STAT- MEDLINE
DCOM- 20201005
LR  - 20201005
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - Accelerated and Severe Lupus Nephritis Benefits From M1, an Active Metabolite of 
      Ginsenoside, by Regulating NLRP3 Inflammasome and T Cell Functions in Mice.
PG  - 1951
LID - 10.3389/fimmu.2019.01951 [doi]
LID - 1951
AB  - Chinese herbal medicines used in combination have long-term been shown to be mild 
      remedies with "integrated effects." However, our study provides the first 
      demonstration that M1, an active metabolite of ginsenoside, exerted its dramatic 
      therapeutic effects on accelerated and severe lupus nephritis (ASLN) mice, 
      featuring acute renal function impairment, heavy proteinuria, high serum levels 
      of anti-dsDNA, and high-grade, diffuse proliferative renal lesions. In the 
      present study, NZB/WF1 mice were given injections of lipopolysaccharide to induce 
      the ASLN model. M1 (30 mg/kg) was then administered to the mice by gavage daily, 
      and the mice were sacrificed on week 3 and week 5 after the induction of disease. 
      To identify the potential mechanism of action for the pure compound, levels of 
      NLRP3 inflammasome activation in bone marrow-derived dendritic cells (BMDCs), 
      podocytes and macrophages, and antigen-specific T cell activation in BMDCs were 
      determined in addition to mechanistic experiments in vivo. Treatment with M1 
      dramatically improved renal function, albuminuria and renal lesions and reduced 
      serum levels of anti-dsDNA in the ASLN mice. These beneficial effects with M1 
      treatment involved the following cellular and molecular mechanistic events: [1] 
      inhibition of NLRP3 inflammasome associated with autophagy induction, [2] 
      modulation of T help cell activation, and [3] induction of regulatory T cell 
      differentiation. M1 improved the ASLN mice by blunting NLRP3 inflammasome 
      activation and differentially regulating T cell functions, and the results 
      support M1 as a new therapeutic candidate for LN patients with a status of abrupt 
      transformation of lower-grade (mesangial) to higher-grade (diffuse proliferative) 
      nephritis.
FAU - Lin, Tsai-Jung
AU  - Lin TJ
AD  - Department of Pathology, National Defense Medical Center, Tri-Service General 
      Hospital, Taipei, Taiwan.
FAU - Wu, Chung-Yao
AU  - Wu CY
AD  - Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, 
      Taiwan.
FAU - Tsai, Pei-Yi
AU  - Tsai PY
AD  - Department of Pathology, National Defense Medical Center, Tri-Service General 
      Hospital, Taipei, Taiwan.
FAU - Hsu, Wan-Han
AU  - Hsu WH
AD  - Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, 
      Taiwan.
FAU - Hua, Kuo-Feng
AU  - Hua KF
AD  - Department of Biotechnology and Animal Science, National Ilan University, Ilan, 
      Taiwan.
FAU - Chu, Ching-Liang
AU  - Chu CL
AD  - Graduate Institute of Immunology, National Taiwan University College of Medicine, 
      Taipei, Taiwan.
FAU - Lee, Yu-Chieh
AU  - Lee YC
AD  - Department of Biotechnology and Animal Science, National Ilan University, Ilan, 
      Taiwan.
FAU - Chen, Ann
AU  - Chen A
AD  - Department of Pathology, National Defense Medical Center, Tri-Service General 
      Hospital, Taipei, Taiwan.
FAU - Lee, Sheau-Long
AU  - Lee SL
AD  - Department of Chemistry, R.O.C. Military Academy, Kaohsiung, Taiwan.
FAU - Lin, Yi-Jin
AU  - Lin YJ
AD  - Department of Pathology, National Defense Medical Center, Tri-Service General 
      Hospital, Taipei, Taiwan.
FAU - Hsieh, Chih-Yu
AU  - Hsieh CY
AD  - Department of Internal Medicine, En Chu Kong Hospital, New Taipei City, Taiwan.
AD  - Renal Care Joint Foundation, New Taipei City, Taiwan.
FAU - Yang, Shin-Ruen
AU  - Yang SR
AD  - Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, 
      Taiwan.
FAU - Liu, Feng-Cheng
AU  - Liu FC
AD  - Division of Rheumatology/Immunology and Allergy, Department of Internal Medicine, 
      National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan.
FAU - Ka, Shuk-Man
AU  - Ka SM
AD  - Graduate Institute of Aerospace and Undersea Medicine, Department of Medicine, 
      National Defense Medical Center, Taipei, Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190814
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (Ginsenosides)
RN  - 0 (Inflammasomes)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
SB  - IM
MH  - Animals
MH  - Antibodies, Antinuclear/blood
MH  - Dendritic Cells/drug effects/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Ginsenosides/*pharmacology
MH  - Humans
MH  - Inflammasomes/*drug effects/metabolism
MH  - Kidney/drug effects/metabolism/physiology
MH  - Lipopolysaccharides
MH  - Lupus Nephritis/chemically induced/*drug therapy/metabolism
MH  - Lymphocyte Activation/drug effects
MH  - Macrophages/drug effects/metabolism
MH  - Mice, Inbred NZB
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Podocytes/drug effects/metabolism
MH  - Signal Transduction/drug effects
MH  - T-Lymphocytes/*drug effects/immunology/metabolism
PMC - PMC6702666
OTO - NOTNLM
OT  - NLRP3 inflammasome
OT  - active metabolite of ginsenoside
OT  - autophagy
OT  - lupus nephritis
OT  - regulatory T cell
EDAT- 2019/09/03 06:00
MHDA- 2020/10/06 06:00
PMCR- 2019/01/01
CRDT- 2019/09/03 06:00
PHST- 2019/04/30 00:00 [received]
PHST- 2019/08/01 00:00 [accepted]
PHST- 2019/09/03 06:00 [entrez]
PHST- 2019/09/03 06:00 [pubmed]
PHST- 2020/10/06 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.01951 [doi]
PST - epublish
SO  - Front Immunol. 2019 Aug 14;10:1951. doi: 10.3389/fimmu.2019.01951. eCollection 
      2019.