PMID- 37146706
OWN - NLM
STAT- MEDLINE
DCOM- 20230522
LR  - 20230522
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 950
DP  - 2023 Jul 5
TI  - The protective effects of sophocarpine on sepsis-induced cardiomyopathy.
PG  - 175745
LID - S0014-2999(23)00256-X [pii]
LID - 10.1016/j.ejphar.2023.175745 [doi]
AB  - This investigation elucidates the impact of sophocarpine treatment on 
      lipopolysaccharide (LPS) stimulated sepsis-induced cardiomyopathy (SIC) via in 
      vivo and in vitro experiments. Echocardiography, ELISA, TUNEL, Western blotting 
      experiments, and Hematoxylin/Eosin, Dihydroethidium, and Immunohistochemistry 
      staining assays, were carried out to identify associated indicators. The 
      echocardiography revealed that sophocarpine treatment alleviated LPS-induced 
      cardiac dysfunction as indicated by fractional shortening shortened and improved 
      ejection fraction. Heart injury biomarkers, such as creatine kinase, lactate 
      dehydrogenase, and creatine kinase-MB, were assessed, and indicated that 
      sophocarpine treatment could alleviate LPS-induced upregulation of these indices. 
      Furthermore, different experimental protocols revealed that sophocarpine 
      treatment inhibits LPS-induced pathological alterations and decreases 
      LPS-stimulated inflammatory cytokines, IL-1beta, monocyte chemoattractant protein-1, 
      IL-6, NOD-like receptor protein-3, and TNF-alpha, increase. Apoptotic proteins such 
      as cytochrome-c, Bax, and cleaved-caspase-3 were increased, and Bcl-2 was 
      alleviated after LPS stimulation; however, these effects were inhibited by 
      sophocarpine treatment. Decreased antioxidant proteins [superoxide dismutase-1 
      (SOD-1) and SOD-2] induced by LPS stimulation were upregulated by sophocarpine 
      treatment. LPS upregulated autophagic proteins such as Beclin-1 and the ratio of 
      microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I and 
      downregulated sequestosome 1 (SQSTM1, or P62), sophocarpine therapy reversed 
      these effects. Moreover, it was indicated that sophocarpine treatment inhibited 
      the Toll-like receptor-4 (TLR-4)/nuclear transcription factor-kappa B (NF-kappaB) 
      signaling pathway and activated nuclear factor erythroid 2-related factor-2 
      (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. In conclusion, sophocarpine 
      treatment could alleviate LPS-trigger SIC by repressing oxidative stress, 
      autophagy, inflammation, and apoptosis via TLR-4/NF-kappaB inhibition and Nrf2/HO-1 
      signaling pathway activation, implicating the potential of sophocarpine as a new 
      therapeutic approach against SIC.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Fu, Yang
AU  - Fu Y
AD  - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang 
      University, Nanchang of Jiangxi, China; Jiangxi Key Laboratory of Molecular 
      Medicine, China.
FAU - Zhang, Hong-Jin
AU  - Zhang HJ
AD  - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang 
      University, Nanchang of Jiangxi, China; Jiangxi Key Laboratory of Molecular 
      Medicine, China.
FAU - Zhou, Wei
AU  - Zhou W
AD  - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang 
      University, Nanchang of Jiangxi, China; Jiangxi Key Laboratory of Molecular 
      Medicine, China.
FAU - Lai, Ze-Qun
AU  - Lai ZQ
AD  - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang 
      University, Nanchang of Jiangxi, China; Jiangxi Key Laboratory of Molecular 
      Medicine, China.
FAU - Dong, Yi-Fei
AU  - Dong YF
AD  - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang 
      University, Nanchang of Jiangxi, China; Jiangxi Key Laboratory of Molecular 
      Medicine, China. Electronic address: yf_dong66@126.com.
LA  - eng
PT  - Journal Article
DEP - 20230503
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (NF-kappa B)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 6483-15-4 (sophocarpine)
RN  - EC 2.7.3.2 (Creatine Kinase)
SB  - IM
MH  - Humans
MH  - NF-kappa B/metabolism
MH  - Toll-Like Receptor 4
MH  - Lipopolysaccharides
MH  - NF-E2-Related Factor 2/metabolism
MH  - *Cardiomyopathies/drug therapy/etiology
MH  - *Sepsis/complications/drug therapy
MH  - Creatine Kinase
OTO - NOTNLM
OT  - Lipopolysaccharide
OT  - Sepsis-induced cardiomyopathy
OT  - Sophocarpine
COIS- Declaration of competing interest None.
EDAT- 2023/05/06 09:42
MHDA- 2023/05/22 06:42
CRDT- 2023/05/05 19:25
PHST- 2023/02/07 00:00 [received]
PHST- 2023/04/10 00:00 [revised]
PHST- 2023/04/24 00:00 [accepted]
PHST- 2023/05/22 06:42 [medline]
PHST- 2023/05/06 09:42 [pubmed]
PHST- 2023/05/05 19:25 [entrez]
AID - S0014-2999(23)00256-X [pii]
AID - 10.1016/j.ejphar.2023.175745 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2023 Jul 5;950:175745. doi: 10.1016/j.ejphar.2023.175745. Epub 
      2023 May 3.