WEI Qiqiu,GAO Si,FENG Yiping,et al.Protective effects of mangiferin against myocardial cell damage and its effects on the expression of NFATc4[J].ZHONGGUO YAOFANG,2023,34(20):2454-2458.
WEI Qiqiu,GAO Si,FENG Yiping,et al.Protective effects of mangiferin against myocardial cell damage and its effects on the expression of NFATc4[J].ZHONGGUO YAOFANG,2023,34(20):2454-2458. DOI: 10.6039/j.issn.1001-0408.2023.20.02.
Protective effects of mangiferin against myocardial cell damage and its effects on the expression of NFATc4
To study the protective effects of mangiferin against oxidative stress injury of myocardial cells induced by hydrogen peroxide (H
2
O
2
), and its effects on the expression of nuclear factor of activated T cell cytoplasmic 4(NFATc4).
METHODS
2
H9c2 myocardial cells were cultured
in vitro
and divided into blank group, H
2
O
2
group, and 50, 100, 150 μmol/L mangiferin groups. Mangiferin groups were treated with different concentrations of mangiferin for 12 h, and then were subjected to H
2
O
2
(200 μmol/L) stimulation for 12 hours together with the H
2
O
2
group; relative survival rate was detected in each group, and the levels of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in cell supernatant and reactive oxygen species (ROS) in H9c2 cells were measured. Meanwhile, the expressions of apoptosis-related proteins [B cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), cleaved caspase-3
]
and nuclear protein NFATc4 were determined. Furthermore, the NFATc4 interference sequence was transfected, and the effects of NFATc4 on oxidant stress indexes and apoptosis-related proteins in H
2
O
2
-induced myocardial cells were investigated.
RESULTS
2
Compared with blank group, relative cell viability, the levels of SOD and CAT, relative expression of Bcl-2 were decreased significantly, while the levels of MDA and ROS, relative expressions of Bax, cleaved caspase-3 and nuclear protein NFATc4 were increased significantly (
P
<0.05 or
P
<0.01). Compared with the H
2
O
2
group, the above indexes of 100 and 150 μmol/L mangiferin groups were reversed significantly (
P
<0.05). After the transfection of the NFATc4 interference sequence, the expression of nuclear protein NFATc4 was down-regulated significantly; the levels of MDA and SOD, the protein expressions of Bax and cleaved caspase-3 were all decreased/down-regulated significantly, while the levels of SOD and CAT, and the protein expression of Bcl-2 were all increased/up-regulated significantly, compared with H
2
O
2
group (
P
<0.05).
CONCLUSIONS
2
Mangiferin can relieve H
2
O
2
-induced oxidative stress of H9c2 cells, reduce the apoptosis and inhibit the nuclear translocation of NFATc4, thereby alleviating myocardial cell damage; reducing the nuclear level of NFATc4 protein is related to reducing H
2
O
2
-induced oxidative stress and cell apoptosis.
关键词
Keywords
references
SAVARESE G , BECHER P M , LUND L H , et al . Global burden of heart failure:a comprehensive and updated review of epidemiology [J ] . Cardiovasc Res , 2023 , 118 ( 17 ): 3272 - 3287 .
WANG X D , ZHANG G Y , DASGUPTA S , et al . ATF4 protects the heart from failure by antagonizing oxidative stress [J ] . Circ Res , 2022 , 131 ( 1 ): 91 - 105 .
KOLIJN D , PABEL S , TIAN Y N , et al . Empagliflozin improves endothelial and cardiomyocyte function in human heart failure with preserved ejection fraction via reduced pro-inflammatory-oxidative pathways and protein kinase Gα oxidation [J ] . Cardiovasc Res , 2021 , 117 ( 2 ): 495 - 507 .
IMRAN M , ARSHAD M S , BUTT M S , et al . Mangi-ferin:a natural miracle bioactive compound against lifestyle related disorders [J ] . Lipids Health Dis , 2017 , 16 ( 1 ): 84 .
JIANG T C , HAN F L , GAO G Y , et al . Mangiferin exert cardioprotective and anti-apoptotic effects in heart failure induced rats [J ] . Life Sci , 2020 , 249 : 117476 .
ZHANG B P , ZHAO J , LI S S , et al . Mangiferin activates the Nrf2-ARE pathway and reduces etoposide-induced DNA damage in human umbilical cord mononuclear blood cells [J ] . Pharm Biol , 2015 , 53 ( 4 ): 503 - 511 .
MAHALANOBISH S , SAHA S , DUTTA S , et al . Mangi-ferin alleviates arsenic induced oxidative lung injury via upregulation of the Nrf2-HO1 axis [J ] . Food Chem Toxicol , 2019 , 126 : 41 - 55 .
ROHINI A , AGRAWAL N , KOYANI C N , et al . Mole-cular targets and regulators of cardiac hypertrophy [J ] . Pharmacol Res , 2010 , 61 ( 4 ): 269 - 280 .
ZHANG Y P , CHEN D Y , ZHAO L P , et al . Nfatc4 deficiency attenuates ototoxicity by suppressing TNF-mediated hair cell apoptosis in the mouse cochlea [J ] . Front Immunol , 2019 , 10 : 1660 .
VAN DER POL A , VAN GILST W H , VOORS A A , et al . Treating oxidative stress in heart failure:past,present and future [J ] . Eur J Heart Fail , 2019 , 21 ( 4 ): 425 - 435 .
WU Q , CHENG K J , YAO H Q , et al . Mangiferin alle-viates hypoxia-induced cell apoptosis in rat primary cultural cardiomyocytes [J ] . Basic Clin Med , 2018 , 38 ( 2 ): 169 - 173 .
QIAN H L , ZHOU S Z , BI X B , et al . Effect of dexmedetomidine regulating Nrf2/HO-1 pathway on H 2 O 2 - induced oxidative stress injury in cardiomyocytes [J ] . China J Mod Med , 2023 , 33 ( 7 ): 40 - 45 .
AIMO A , CASTIGLIONE V , BORRELLI C , et al . Oxidative stress and inflammation in the evolution of heart fai-lure:from pathophysiology to therapeutic strategies [J ] . Eur J Prev Cardiol , 2020 , 27 ( 5 ): 494 - 510 .
ALI A , RASHID M A , HUANG Q Y , et al . Influence of UV-A radiation on oxidative stress and antioxidant enzymes in Mythimna separata (Lepidoptera:Noctuidae) [J ] . Environ Sci Pollut Res Int , 2017 , 24 ( 9 ): 8392 - 8398 .
LIU G L , LEI J J , LONG Z , et al . Protective effect of mangiferin on rats with chronic heart failure via Nrf2/HO-1 signal pathway [J ] . Prog Anat Sci , 2022 , 28 ( 1 ): 26 - 30 .
XU Q , DALIC A , FANG L , et al . Myocardial oxidative stress contributes to transgenic β₂-adrenoceptor activation-induced cardiomyopathy and heart failure [J ] . Br J Pharmacol , 2011 , 162 ( 5 ): 1012 - 1028 .
ROUCOU X , GIANNOPOULOS P N , ZHANG Y , et al . Cellular prion protein inhibits proapoptotic Bax conformational change in human neurons and in breast carcinoma MCF-7 cells [J ] . Cell Death Differ , 2005 , 12 ( 7 ): 783 - 795 .
SHEN X J , WANG H B , WENG C H , et al . Caspase 3/GSDME-dependent pyroptosis contributes to chemothe-rapy drug-induced nephrotoxicity [J ] . Cell Death Dis , 2021 , 12 ( 2 ): 186 .
MARQUES C M S , PEDRON T , BATISTA B L , et al . Cellular prion protein activates caspase 3 for apoptotic defense mechanism in astrocytes [J ] . Mol Cell Biochem , 2021 , 476 ( 5 ): 2149 - 2158 .
BUSHDID P B , OSINSKA H , WACLAW R R , et al . NFATc 3 and NFATc 4 are required for cardiac development and mitochondrial function [J ] . Circ Res , 2003 , 92 ( 12 ): 1305 - 1313 .
LI L , KE K F , TAN X , et al . Up-regulation of NFATc 4 involves in neuronal apoptosis following intracerebral he-morrhage [J ] . Cell Mol Neurobiol , 2013 , 33 ( 7 ): 893 - 905 .