PMID- 34675994
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211023
IS  - 1792-1015 (Electronic)
IS  - 1792-0981 (Print)
IS  - 1792-0981 (Linking)
VI  - 22
IP  - 6
DP  - 2021 Dec
TI  - Protective effects of safranal on hypoxia/reoxygenation-induced injury in H9c2 
      cardiac myoblasts via the PI3K/AKT/GSK3beta signaling pathway.
PG  - 1400
LID - 10.3892/etm.2021.10836 [doi]
LID - 1400
AB  - Safranal (SFR), an active ingredient extracted from saffron, exhibits a 
      protective effect on the cardiovascular system. However, the mechanism of SFR 
      against hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury has previously 
      not been investigated in vitro. The aim of the present study was therefore to 
      observe the protective effects of SFR on H/R-induced cardiomyocyte injury and to 
      explore its mechanisms. A H/R injury model of H9c2 cardiac myoblasts was 
      established by administering 800 micromol/l CoCl(2) to H9c2 cells for 24 h and 
      reoxygenating the cells for 4 h to induce hypoxia. H9c2 cardiac myoblasts were 
      pretreated with SFR for 12 h to evaluate the associated protective effects. A 
      Cell Counting Kit-8 assay was used for cell viability detection, and the 
      expression levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), 
      glutathione peroxidase (GSH-px), catalase (CAT), superoxide dismutase (SOD), 
      malondialdehyde (MDA) and caspase-3, and the intracellular Ca(2+) concentration 
      were measured using the corresponding commercial kits. Levels of reactive oxygen 
      species (ROS) in the cells were detected using 2,7-dichlorodihydrofluorescein 
      diacetate. Flow cytometry was used to determine the degree of apoptosis and the 
      level of mitochondrial membrane potential (MMP). Moreover, the expression levels 
      of phosphorylated (p-)PI3K, AKT, p-AKT, glycogen synthase kinase 3beta (GSK3beta), 
      p-GSK3beta, Bcl-2, Bax, caspase-3 and cleaved caspase-3 were measured using western 
      blot analysis. Results of the present study demonstrated that the H9c2 cardiac 
      myoblasts treated with SFR exhibited significantly improved levels of viability 
      and significantly reduced levels of ROS, compared with the H/R group. 
      Furthermore, compared with the H/R group, SFR treatment significantly increased 
      the MMP levels and antioxidant enzyme levels, including CAT, SOD and GSH-px; 
      whereas the levels of CK-MB, LDH, MDA and intracellular Ca(2+) concentration were 
      significantly decreased. Moreover, the results of the present study demonstrated 
      that SFR significantly reduced caspase-3, cleaved caspase-3 and Bax protein 
      expression levels, but upregulated the Bcl-2 protein expression levels. SFR also 
      increased the protein expressions of PI3K/AKT/GSK3beta. In summary, the results 
      suggested that SFR may exert a protective effect against H/R-induced 
      cardiomyocyte injury, which occurs in connection with the inhibition of oxidative 
      stress and apoptosis via regulation of the PI3K/AKT/GSK3beta signaling pathway.
CI  - Copyright: (c) Wang et al.
FAU - Wang, Hefei
AU  - Wang H
AD  - Department of Traditional Chinese Medicine and Medical History Literature, School 
      of Basic Medicine, Shijiazhuang, Hebei 050200, P.R. China.
FAU - Zheng, Bin
AU  - Zheng B
AD  - Department of Traditional Chinese Medicine, School of Pharmacy, Hebei University 
      of Chinese Medicine, Shijiazhuang, Hebei 050200, P.R. China.
FAU - Che, Kaimeng
AU  - Che K
AD  - Department of Traditional Chinese Medicine and Medical History Literature, School 
      of Basic Medicine, Shijiazhuang, Hebei 050200, P.R. China.
FAU - Han, Xue
AU  - Han X
AD  - Department of Traditional Chinese Medicine and Medical History Literature, School 
      of Basic Medicine, Shijiazhuang, Hebei 050200, P.R. China.
FAU - Li, Li
AU  - Li L
AD  - Department of Pharmacognosy, School of Pharmacy, Hebei Medical University, 
      Shijiazhuang, Hebei 050200, P.R. China.
FAU - Wang, Hongfang
AU  - Wang H
AD  - Department of Traditional Chinese Medicine, School of Pharmacy, Hebei University 
      of Chinese Medicine, Shijiazhuang, Hebei 050200, P.R. China.
FAU - Liu, Yanshuang
AU  - Liu Y
AD  - Department of Diagnostics, Hebei Key Laboratory of Integrative Medicine on 
      Liver-Kidney Patterns, Institute of Integrative Medicine, College of Integrative 
      Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, P.R. 
      China.
FAU - Shi, Jing
AU  - Shi J
AD  - Department of Scientific Research Management, The Fourth Hospital of Hebei 
      Medical University, Shijiazhuang, Hebei 050011, P.R. China.
FAU - Sun, Shijiang
AU  - Sun S
AD  - Department of Hospital Management and Medical History Literature, Hebei Province 
      Hospital of Chinese Medicine, The First Affiliated Hospital, Hebei University of 
      Chinese Medicine, Shijiazhuang, Hebei 050200, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20211001
PL  - Greece
TA  - Exp Ther Med
JT  - Experimental and therapeutic medicine
JID - 101531947
PMC - PMC8524664
OTO - NOTNLM
OT  - H9c2 cardiac myoblasts
OT  - PI3K/AKT/GSK3beta signaling pathway
OT  - anti-apoptosis
OT  - anti-oxidant stress
OT  - hypoxia/reoxygenation
OT  - safranal
EDAT- 2021/10/23 06:00
MHDA- 2021/10/23 06:01
PMCR- 2021/10/01
CRDT- 2021/10/22 06:49
PHST- 2021/05/13 00:00 [received]
PHST- 2021/09/14 00:00 [accepted]
PHST- 2021/10/22 06:49 [entrez]
PHST- 2021/10/23 06:00 [pubmed]
PHST- 2021/10/23 06:01 [medline]
PHST- 2021/10/01 00:00 [pmc-release]
AID - ETM-22-6-10836 [pii]
AID - 10.3892/etm.2021.10836 [doi]
PST - ppublish
SO  - Exp Ther Med. 2021 Dec;22(6):1400. doi: 10.3892/etm.2021.10836. Epub 2021 Oct 1.