Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Curcuminoids Attenuate Myocardial Ischemia-Reperfusion Injury by Regulating Total RNA M6a Levels: In Vitro Study

Author(s): Jian-Kun Cui, Xin Wang, Mingming Fan* and Qinwen Wang*

Volume 26, Issue 10, 2023

Published on: 17 November, 2022

Page: [1848 - 1855] Pages: 8

DOI: 10.2174/1386207325666220929141003

Price: $65

conference banner
Abstract

Objective: Myocardial ischemia-reperfusion (IR) injury is an unresolved medical problem with a high incidence. This study aims to analyze the novel molecular mechanism by which curcuminoids protect cardiomyocytes from IR injury.

Methods: A IR model In Vitro of rat cardiomyocytes H9c2 cells was structured. Curcumin (CUR) and its derivatives, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) treated H9c2 cells, and reactive oxygen species (ROS) production, viability, apoptosis, mitochondrial membrane potential (MMP), oxidative stress and total RNA m6A levels of H9c2 cells were detected by using DCFH-DA stain, CCK-8, flow cytometry, Hoechst 33342 stain, TMRM stain, ELISA and RTqPCR. FB23 was used in rescue experiments.

Results: IR significantly increased ROS production, decreased cell viability, and induced apoptosis, MMP loss, and oxidative stress. In addition, IR induced an increase in total RNA m6A levels and changes in m6A-related proteins expression. CUR (10 μM), DMC (10 μM) and BDMC (10 μM), significantly inhibited IR-induced ROS production, apoptosis, MMP loss and oxidative stress, and enhanced cell viability. Furthermore, CUR, DMC and BDMC altered the expression pattern of m6A-related proteins and reduced IR-induced total m6A levels. There was no significant difference in the effects of the three. CUR's protective effect was partially reduced by FB23.

Conclusion: Curcuminoids attenuate myocardial IR injury by regulating total RNA m6A levels.

Keywords: Curcumin, demethoxycurcumin, bisdemethoxycurcumin, myocardial ischemia-reperfusion, RNA m6A

« Previous Next »
Graphical Abstract

[1]
Kalogeris, T.; Baines, C.P.; Krenz, M.; Korthuis, R.J. Ischemia/reperfusion. Compr. Physiol., 2016, 7(1), 113-170.
[http://dx.doi.org/10.1002/cphy.c160006] [PMID: 28135002]
[2]
Bagheri, F.; Khori, V.; Alizadeh, A.M.; Khalighfard, S.; Khodayari, S.; Khodayari, H. Reactive oxygen species-mediated cardiac-reperfusion injury: Mechanisms and therapies. Life Sci., 2016, 165, 43-55.
[http://dx.doi.org/10.1016/j.lfs.2016.09.013] [PMID: 27667751]
[3]
Kuznetsov, A.V.; Javadov, S.; Margreiter, R.; Grimm, M.; Hagenbuchner, J.; Ausserlechner, M.J. The role of mitochondria in the mechanisms of cardiac ischemia-reperfusion injury. Antioxidants, 2019, 8(10), 454.
[http://dx.doi.org/10.3390/antiox8100454] [PMID: 31590423]
[4]
Bronicki, R.A.; Hall, M. Cardiopulmonary bypass-induced inflammatory response. Pediatr. Crit. Care Med., 2016, 17(8)(Suppl. 1), S272-S278.
[http://dx.doi.org/10.1097/PCC.0000000000000759] [PMID: 27490610]
[5]
Gupta, S.C.; Patchva, S.; Aggarwal, B.B. Therapeutic roles of curcumin: Lessons learned from clinical trials. AAPS J., 2013, 15(1), 195-218.
[http://dx.doi.org/10.1208/s12248-012-9432-8] [PMID: 23143785]
[6]
Huang, Z.; Ye, B.; Dai, Z.; Wu, X.; Lu, Z.; Shan, P.; Huang, W. Curcumin inhibits autophagy and apoptosis in hypoxia/reoxygenation-induced myocytes. Mol. Med. Rep., 2015, 11(6), 4678-4684.
[http://dx.doi.org/10.3892/mmr.2015.3322] [PMID: 25673156]
[7]
Ilyas, E.I.I.; Nur, B.M.; Laksono, S.P.; Bahtiar, A.; Estuningtyas, A.; Vitasyana, C.; Kusmana, D.; Suyatna, F.D.; Tadjudin, M.K.; Freisleben, H.J. Effects of curcumin on parameters of myocardial oxidative stress and of mitochondrial glutathione turnover in reoxygenation after 60 minutes of hypoxia in isolated perfused working guinea pig hearts. Adv. Pharmacol. Sci., 2016, 2016, 1-10.
[http://dx.doi.org/10.1155/2016/6173648] [PMID: 26904113]
[8]
Jiankun Cui, N.G.; Meng, F.; Shi, L.; Tian, G.; Yang, G. Demethoxycurcumin regulates autophagy through PI3K-Akt-mTOR signaling pathway to protect myocardial ischemia-reperfusion injury in rats. J. Chin. Med., 2020, 48(8), 5.
[http://dx.doi.org/10.19664/j.cnki.1002-2392.200137]
[9]
Song, H.; Feng, X.; Zhang, H.; Luo, Y.; Huang, J.; Lin, M.; Jin, J.; Ding, X.; Wu, S.; Huang, H.; Yu, T.; Zhang, M.; Hong, H.; Yao, S.; Zhao, Y.; Zhang, Z. METTL3 and ALKBH5 oppositely regulate m 6 A modification of TFEB mRNA, which dictates the fate of hypoxia/reoxygenation-treated cardiomyocytes. Autophagy, 2019, 15(8), 1419-1437.
[http://dx.doi.org/10.1080/15548627.2019.1586246] [PMID: 30870073]
[10]
Mathiyalagan, P.; Adamiak, M.; Mayourian, J.; Sassi, Y.; Liang, Y.; Agarwal, N.; Jha, D.; Zhang, S.; Kohlbrenner, E.; Chepurko, E.; Chen, J.; Trivieri, M.G.; Singh, R.; Bouchareb, R.; Fish, K.; Ishikawa, K.; Lebeche, D.; Hajjar, R.J.; Sahoo, S. FTO-dependent N 6 -methyladenosine regulates cardiac function during remodeling and repair. Circulation, 2019, 139(4), 518-532.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.033794] [PMID: 29997116]
[11]
Wang, R.; Zhang, J.Y.; Zhang, M.; Zhai, M.G.; Di, S.Y.; Han, Q.H.; Jia, Y.P.; Sun, M.; Liang, H.L. Curcumin attenuates IR-induced myocardial injury by activating SIRT3. Eur. Rev. Med. Pharmacol. Sci., 2018, 22(4), 1150-1160.
[http://dx.doi.org/10.26355/eurrev_201802_14404] [PMID: 29509269]
[12]
Chen, L.S.; Zhang, M.; Chen, P.; Xiong, X.F.; Liu, P.Q.; Wang, H.B. The m(6)A demethylase FTO promotes the osteogenesis of mesenchymal stem cells by downregulating PPARG. Acta Pharmacol. Sin., 2021.
[http://dx.doi.org/10.1038/s41401-021-00756-8] [PMID: 34462564]
[13]
Jiang, S.; Han, J.; Li, T.; Xin, Z.; Ma, Z.; Di, W.; Hu, W.; Gong, B.; Di, S.; Wang, D.; Yang, Y. Curcumin as a potential protective compound against cardiac diseases. Pharmacol. Res., 2017, 119, 373-383.
[http://dx.doi.org/10.1016/j.phrs.2017.03.001] [PMID: 28274852]
[14]
Abdollahi, E.; Momtazi, A.A.; Johnston, T.P.; Sahebkar, A. Therapeutic effects of curcumin in inflammatory and immune‐mediated diseases: A nature‐made jack‐of‐all‐trades? J. Cell. Physiol., 2018, 233(2), 830-848.
[http://dx.doi.org/10.1002/jcp.25778] [PMID: 28059453]
[15]
Momtazi, A.A.; Shahabipour, F.; Khatibi, S.; Johnston, T.P.; Pirro, M.; Sahebkar, A. Curcumin as a MicroRNA regulator in cancer: A review. Rev. Physiol. Biochem. Pharmacol., 2016, 171, 1-38.
[http://dx.doi.org/10.1007/112_2016_3] [PMID: 27457236]
[16]
Ji, X.; Xiao, J.; Sheng, X.; Zhang, X.; Guo, M. Curcumin protects against myocardial infarction-induced cardiac fibrosis via SIRT1 activation in vivo and in vitro. Drug Des. Devel. Ther., 2016, 10, 1267-1277.
[http://dx.doi.org/10.2147/DDDT.S104925] [PMID: 27099472]
[17]
Jonkhout, N.; Tran, J.; Smith, M.A.; Schonrock, N.; Mattick, J.S.; Novoa, E.M. The RNA modification landscape in human disease. RNA, 2017, 23(12), 1754-1769.
[http://dx.doi.org/10.1261/rna.063503.117] [PMID: 28855326]
[18]
Batista, P.J. The RNA modification N 6 -methyladenosine and its implications in human disease. Genom. Proteom. Bioinform., 2017, 15(3), 154-163.
[http://dx.doi.org/10.1016/j.gpb.2017.03.002] [PMID: 28533023]
[19]
Liu, R.J.; Long, T.; Li, J.; Li, H.; Wang, E.D. Structural basis for substrate binding and catalytic mechanism of a human RNA:m5C methyltransferase NSun6. Nucleic Acids Res., 2017, 45(11), 6684-6697.
[http://dx.doi.org/10.1093/nar/gkx473] [PMID: 28531330]
[20]
Glasner, H.; Riml, C.; Micura, R.; Breuker, K. Label-free, direct localization and relative quantitation of the RNA nucleobase methylations m6A, m5C, m3U, and m5U by top-down mass spectrometry. Nucleic Acids Res., 2017, 45(13), 8014-8025.
[http://dx.doi.org/10.1093/nar/gkx470] [PMID: 28549193]
[21]
Malbec, L.; Zhang, T.; Chen, Y.S.; Zhang, Y.; Sun, B.F.; Shi, B.Y.; Zhao, Y.L.; Yang, Y.; Yang, Y.G. Dynamic methylome of internal mRNA N7-methylguanosine and its regulatory role in translation. Cell Res., 2019, 29(11), 927-941.
[http://dx.doi.org/10.1038/s41422-019-0230-z] [PMID: 31520064]
[22]
Yang, Y.; Duan, W.; Lin, Y.; Yi, W.; Liang, Z.; Yan, J.; Wang, N.; Deng, C.; Zhang, S.; Li, Y.; Chen, W.; Yu, S.; Yi, D.; Jin, Z. SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury. Free Radic. Biol. Med., 2013, 65, 667-679.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.07.007] [PMID: 23880291]
[23]
Dutta, B.; Rawoota, Y.A.; Checker, S.; Shelar, S.B.; Barick, K.C; Kumar, S; Somani, R.R; Hassan, P.A Micellar assisted aqueous stabilization of iron oxide nanoparticles for curcumin encapsulation and hyperthermia application. Nano-Structures & Nano-Objects, 2020, 22, 100466.
[24]
Prasad, S.; Gupta, S.C.; Tyagi, A.K.; Aggarwal, B.B. Curcumin, a component of golden spice: From bedside to bench and back. Biotechnol. Adv., 2014, 32(6), 1053-1064.
[http://dx.doi.org/10.1016/j.biotechadv.2014.04.004] [PMID: 24793420]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy