PMID- 38153125
OWN - NLM
STAT- MEDLINE
DCOM- 20240215
LR  - 20240215
IS  - 1099-1573 (Electronic)
IS  - 0951-418X (Linking)
VI  - 38
IP  - 2
DP  - 2024 Feb
TI  - Astilbin protects from sepsis-induced cardiac injury through the NRF2/HO-1 and 
      TLR4/NF-kappaB pathway.
PG  - 1044-1058
LID - 10.1002/ptr.8093 [doi]
AB  - Cardiac dysfunction and arrhythmia are severe complications of sepsis-induced 
      cardiomyopathy and are associated with an increased risk of morbidity and 
      mortality. Currently, the precise mechanism for sepsis-induced myocardial damage 
      remains unclear. Astilbin, a flavonoid, is reported to have anti-inflammatory, 
      antioxidative, and antiapoptotic properties. However, the effects of astilbin on 
      sepsis-induced cardiomyopathy have not been studied so far. This study aims to 
      investigate the effect of astilbin in sepsis-induced myocardial injury and 
      elucidate the underlying mechanism. In vivo and in vitro sepsis models were 
      created using lipopolysaccharide (LPS) as an inducer in H9C2 cardiomyocytes and 
      C57BL/6 mice, respectively. Our results demonstrated that astilbin reduced 
      myocardial injury and improved cardiac function. Moreover, astilbin prolonged the 
      QT and corrected QT intervals, attenuated myocardial electrical remodeling, and 
      promoted gap junction protein (Cx43) and ion channels expression, thereby 
      reducing the susceptibility of ventricular fibrillation. In addition, astilbin 
      alleviated LPS-induced inflammation, oxidative stress, and apoptosis. Astilbin 
      suppressed the toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-kappaB) pathway in 
      vivo and in vitro models. Astilbin remarkedly upregulated the nuclear factor 
      erythroid 2-related factor 2 (NRF2) and heme oxygenase 1 (HO-1) expression. The 
      in vitro treatment with an NRF2 inhibitor reversed the inhibition of the 
      TLR4/NF-kappaB pathway and antioxidant properties of astilbin. Astilbin attenuated 
      LPS-induced myocardial injury, cardiac dysfunction, susceptibility to VF, 
      inflammation, oxidative stress, and apoptosis by activating the NRF2/HO-1 pathway 
      and inhibiting TLR4/ NF-kappaB pathway. These results suggest that astilbin could be 
      an effective and promising therapeutics target for the treatment of 
      sepsis-induced cardiomyopathy.
CI  - (c) 2023 John Wiley & Sons Ltd.
FAU - Fang, Zhao
AU  - Fang Z
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, China.
FAU - Wang, Guangji
AU  - Wang G
AD  - Department of Cardiology, The Central Hospital of Wuhan, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, China.
FAU - Huang, Rui
AU  - Huang R
AD  - Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao 
      Autonomous Prefecture, Enshi, China.
AD  - Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia 
      and Miao Autonomous Prefecture, Enshi, China.
AD  - Hubei Provincial Key Lab of Selenium Resources and Bioapplications, Enshi, China.
FAU - Liu, Chengyin
AU  - Liu C
AUID- ORCID: 0000-0002-4816-152X
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, China.
FAU - Yushanjiang, Feierkaiti
AU  - Yushanjiang F
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, China.
FAU - Mao, Tuohua
AU  - Mao T
AD  - Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, China.
FAU - Li, Jun
AU  - Li J
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, China.
LA  - eng
GR  - 82100866/Nature Science Foundation of China/
GR  - 82160072/Nature Science Foundation of China/
GR  - 82360085/Nature Science Foundation of China/
GR  - 2023020201020539/Wuhan Knowledge Innovation Special Dawn Plan Project/
PT  - Journal Article
DEP - 20231228
PL  - England
TA  - Phytother Res
JT  - Phytotherapy research : PTR
JID - 8904486
RN  - 0 (NF-kappa B)
RN  - 0 (Toll-Like Receptor 4)
RN  - 29838-67-3 (astilbin)
RN  - 0 (NF-E2-Related Factor 2)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Antioxidants)
RN  - 0 (Flavonols)
SB  - IM
MH  - Mice
MH  - Animals
MH  - NF-kappa B/metabolism
MH  - Toll-Like Receptor 4/metabolism
MH  - Signal Transduction
MH  - NF-E2-Related Factor 2/metabolism
MH  - Heme Oxygenase-1/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Mice, Inbred C57BL
MH  - Inflammation
MH  - Oxidative Stress
MH  - Antioxidants/pharmacology/metabolism
MH  - *Heart Diseases
MH  - *Cardiomyopathies/drug therapy
MH  - *Sepsis/complications/drug therapy
MH  - *Flavonols
OTO - NOTNLM
OT  - NRF2/HO-1
OT  - TLR4/NF-kappaB
OT  - arrhythmia
OT  - astilbin
OT  - cardiac dysfunction
EDAT- 2023/12/28 12:42
MHDA- 2024/02/15 06:43
CRDT- 2023/12/28 07:59
PHST- 2023/11/10 00:00 [revised]
PHST- 2023/05/25 00:00 [received]
PHST- 2023/11/28 00:00 [accepted]
PHST- 2024/02/15 06:43 [medline]
PHST- 2023/12/28 12:42 [pubmed]
PHST- 2023/12/28 07:59 [entrez]
AID - 10.1002/ptr.8093 [doi]
PST - ppublish
SO  - Phytother Res. 2024 Feb;38(2):1044-1058. doi: 10.1002/ptr.8093. Epub 2023 Dec 28.