PMID- 38453210
OWN - NLM
STAT- MEDLINE
DCOM- 20240506
LR  - 20240506
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Linking)
VI  - 172
IP  - 2
DP  - 2024 Jun
TI  - Flavonoid extracted from Epimedium attenuate cGAS-STING-mediated diseases by 
      targeting the formation of functional STING signalosome.
PG  - 295-312
LID - 10.1111/imm.13771 [doi]
AB  - Hyperactivation of the cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon 
      genes (STING) signalling pathway has been shown to be associated with the 
      development of a variety of inflammatory diseases, and the discovery of an 
      inhibitor of the cGAS-STING signalling pathway holds great promise in the 
      therapeutic interventions. Epimedium flavonoid (EF), a major active ingredient 
      isolated from the medicinal plant Epimedium, has been reported to have good 
      anti-inflammatory activity, but its exact mechanism of action remains unclear. In 
      the present study, we found that EF in mouse bone marrow-derived macrophages 
      (BMDMs), THP-1 (Tohoku Hospital Pediatrics-1) as well as in human peripheral 
      blood mononuclear cells (hPBMC) inhibited the activation of the cGAS-STING 
      signalling pathway, which subsequently led to a decrease in the expression of 
      type I interferon (IFN-beta, CXCL10 and ISG15) and pro-inflammatory cytokines (IL-6 
      and TNF-alpha). Mechanistically, EF does not affect STING oligomerization, but 
      inhibits the formation of functional STING signalosome by attenuating the 
      interaction of interferon regulatory factor 3 (IRF3) with STING and TANK-binding 
      kinase 1 (TBK1). Importantly, in vivo experiments, EF has shown promising 
      therapeutic effects on inflammatory diseases mediated by the cGAS-STING pathway, 
      which include the agonist model induced by DMXAA stimulation, the autoimmune 
      inflammatory disease model induced by three prime repair exonuclease 1 (Trex1) 
      deficiency, and the non-alcoholic steatohepatitis (NASH) model induced by a 
      pathogenic amino acid and choline deficiency diet (MCD). To summarize, our study 
      suggests that EF is a potent potential inhibitor component of the cGAS-STING 
      signalling pathway for the treatment of inflammatory diseases mediated by the 
      cGAS-STING signalling pathway.
CI  - (c) 2024 John Wiley & Sons Ltd.
FAU - Wang, Yan
AU  - Wang Y
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, 
      Beijing, China.
AD  - Department of Hepatology, The Fifth Medical Center of Chinese PLA General 
      Hospital, Beijing, China.
AD  - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA 
      General Hospital, Beijing, China.
FAU - Xu, Guang
AU  - Xu G
AD  - School of Traditional Chinese Medicine, Capital Medical University, Beijing, 
      China.
FAU - Wen, Jincai
AU  - Wen J
AD  - Department of Hepatology, The Fifth Medical Center of Chinese PLA General 
      Hospital, Beijing, China.
AD  - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA 
      General Hospital, Beijing, China.
FAU - Zhao, Xiaomei
AU  - Zhao X
AD  - Department of Hepatology, The Fifth Medical Center of Chinese PLA General 
      Hospital, Beijing, China.
AD  - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA 
      General Hospital, Beijing, China.
FAU - Zhao, Huanying
AU  - Zhao H
AD  - Core Facilities Center, Capital Medical University, Beijing, China.
FAU - Lv, Guiji
AU  - Lv G
AD  - Department of Hepatology, The Fifth Medical Center of Chinese PLA General 
      Hospital, Beijing, China.
AD  - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA 
      General Hospital, Beijing, China.
FAU - Xu, Yingjie
AU  - Xu Y
AD  - Department of Hepatology, The Fifth Medical Center of Chinese PLA General 
      Hospital, Beijing, China.
AD  - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA 
      General Hospital, Beijing, China.
FAU - Xiu, Ye
AU  - Xiu Y
AD  - Department of Hepatology, The Fifth Medical Center of Chinese PLA General 
      Hospital, Beijing, China.
AD  - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA 
      General Hospital, Beijing, China.
FAU - Li, Junjie
AU  - Li J
AD  - Department of Hepatology, The Fifth Medical Center of Chinese PLA General 
      Hospital, Beijing, China.
AD  - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA 
      General Hospital, Beijing, China.
FAU - Chen, Simin
AU  - Chen S
AD  - Department of Hepatology, The Fifth Medical Center of Chinese PLA General 
      Hospital, Beijing, China.
AD  - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA 
      General Hospital, Beijing, China.
FAU - Yao, Qing
AU  - Yao Q
AD  - Department of Hepatology, The Fifth Medical Center of Chinese PLA General 
      Hospital, Beijing, China.
AD  - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA 
      General Hospital, Beijing, China.
FAU - Chen, Yuanyuan
AU  - Chen Y
AD  - Department of Hepatology, The Fifth Medical Center of Chinese PLA General 
      Hospital, Beijing, China.
AD  - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA 
      General Hospital, Beijing, China.
FAU - Ma, Lina
AU  - Ma L
AD  - Department of Pharmacy, Dongfang Hospital Affiliated to Beijing University of 
      Chinese Medicine, Beijing, China.
FAU - Xiao, Xiaohe
AU  - Xiao X
AD  - Department of Hepatology, The Fifth Medical Center of Chinese PLA General 
      Hospital, Beijing, China.
AD  - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA 
      General Hospital, Beijing, China.
FAU - Cao, Junling
AU  - Cao J
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, 
      Beijing, China.
AD  - Department of Pharmacy, Dongzhimen Hospital Affiliated to Beijing University of 
      Chinese Medicine, Beijing, China.
FAU - Bai, Zhaofang
AU  - Bai Z
AUID- ORCID: 0000-0002-6208-150X
AD  - Department of Hepatology, The Fifth Medical Center of Chinese PLA General 
      Hospital, Beijing, China.
AD  - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA 
      General Hospital, Beijing, China.
LA  - eng
GR  - 7232321/Beijing Natural Science Foundation of Beijing/
GR  - ZYYCXTD-C-202005/Innovation Team and Talents Cultivation Program of National 
      Administration of Traditional Chinese Medicine/
GR  - CFH 2022-4-5062/Capital's Funds for Health Improvement and Research, China/
GR  - 2021ZY046/General Project of Special Plan for Cultivation and Promotion of TCM 
      Service/
GR  - 23BJZ33/Traditional Chinese Medicine/
GR  - 81930110/State Key Program of National Natural Science of China/
GR  - 82230118/State Key Program of National Natural Science of China/
GR  - 81874368/State Key Program of National Natural Science of China/
GR  - 81721002/Foundation for Innovative Research Groups of the National Natural 
      Science Foundation of China/
GR  - 2060302/Key Project at Central Government Level: The Ability Establishment of 
      Sustainable Use for Valuable Chinese Medicine Resources/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20240307
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - EC 2.7.7.- (Nucleotidyltransferases)
RN  - 0 (Membrane Proteins)
RN  - 0 (Flavonoids)
RN  - 0 (Sting1 protein, mouse)
RN  - 0 (STING1 protein, human)
RN  - 0 (Interferon Regulatory Factor-3)
RN  - EC 2.7.7.- (cGAS protein, mouse)
RN  - 0 (Cytokines)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.7.- (cGAS protein, human)
RN  - EC 2.7.1.- (Tbk1 protein, mouse)
RN  - 0 (Anti-Inflammatory Agents)
SB  - IM
MH  - *Nucleotidyltransferases/metabolism
MH  - *Membrane Proteins/metabolism
MH  - Animals
MH  - *Signal Transduction/drug effects
MH  - Humans
MH  - Mice
MH  - *Flavonoids/pharmacology
MH  - *Epimedium/chemistry
MH  - Interferon Regulatory Factor-3/metabolism
MH  - Macrophages/metabolism/immunology/drug effects
MH  - Mice, Inbred C57BL
MH  - Cytokines/metabolism
MH  - THP-1 Cells
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Leukocytes, Mononuclear/metabolism/immunology/drug effects
OTO - NOTNLM
OT  - Epimedium flavonoid
OT  - autoimmune diseases
OT  - cGAS-STING
OT  - inflammatory diseases
OT  - non-alcoholic steatohepatitis
EDAT- 2024/03/08 00:43
MHDA- 2024/05/07 00:50
CRDT- 2024/03/07 20:43
PHST- 2023/09/11 00:00 [received]
PHST- 2024/02/19 00:00 [accepted]
PHST- 2024/05/07 00:50 [medline]
PHST- 2024/03/08 00:43 [pubmed]
PHST- 2024/03/07 20:43 [entrez]
AID - 10.1111/imm.13771 [doi]
PST - ppublish
SO  - Immunology. 2024 Jun;172(2):295-312. doi: 10.1111/imm.13771. Epub 2024 Mar 7.