IgA Nephropathy Benefits from Compound K Treatment by Inhibiting NF-κB/NLRP3 Inflammasome and Enhancing Autophagy and SIRT1.
Animals
Autophagy
/ drug effects
Cell Line
Dendritic Cells
/ drug effects
Disease Models, Animal
Ginsenosides
/ pharmacology
Glomerulonephritis, IGA
/ drug therapy
Humans
Inflammasomes
/ antagonists & inhibitors
Kidney Glomerulus
/ drug effects
Macrophages
/ immunology
Mice
Mice, Inbred Strains
NF-kappa B
/ metabolism
NLR Family, Pyrin Domain-Containing 3 Protein
/ metabolism
Primary Cell Culture
Signal Transduction
/ drug effects
Sirtuin 1
/ metabolism
Journal
Journal of immunology (Baltimore, Md. : 1950)
ISSN: 1550-6606
Titre abrégé: J Immunol
Pays: United States
ID NLM: 2985117R
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
received:
11
03
2019
accepted:
24
04
2020
pubmed:
3
6
2020
medline:
12
3
2021
entrez:
3
6
2020
Statut:
ppublish
Résumé
IgA nephropathy (IgAN), the most common primary glomerular disorder, has a relatively poor prognosis yet lacks a pathogenesis-based treatment. Compound K (CK) is a major absorbable intestinal bacterial metabolite of ginsenosides, which are bioactive components of ginseng. The present study revealed promising therapeutic effects of CK in two complementary IgAN models: a passively induced one developed by repeated injections of IgA immune complexes and a spontaneously occurring model of spontaneous grouped ddY mice. The potential mechanism for CK includes 1) inhibiting the activation of NLRP3 inflammasome in renal tissues, macrophages and bone marrow-derived dendritic cells, 2) enhancing the induction of autophagy through increased SIRT1 expression, and 3) eliciting autophagy-mediated NLRP3 inflammasome inhibition. The results support CK as a drug candidate for IgAN.
Identifiants
pubmed: 32482710
pii: jimmunol.1900284
doi: 10.4049/jimmunol.1900284
doi:
Substances chimiques
Ginsenosides
0
Inflammasomes
0
NF-kappa B
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
Nlrp3 protein, mouse
0
ginsenoside M1
A9RLM212CY
Sirt1 protein, mouse
EC 3.5.1.-
Sirtuin 1
EC 3.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
202-212Informations de copyright
Copyright © 2020 by The American Association of Immunologists, Inc.