Coptisine alleviates ischemia/reperfusion-induced myocardial damage by regulating apoptosis-related proteins
Introduction
Ischemic heart disease (IHD) is one of the main causes of disability and death worldwide (Crea et al., 2015; Dalen et al., 2014). The occurrence of the disease is caused by long-term serious coronary artery insufficiency of blood and oxygen, which contributes to the development of nutritional disorders of myocardial tissue and cardiomyocytes apoptosis, induces myocardial dysfunction, heart failure, thereby ultimately leading to the death of patients (Khera and Kathiresan, 2017). At present, the main treatment of IHD is to restore myocardial blood supply. Ischemia/reperfusion (I/R) refers to the injuries to the structure and function of myocardial tissue after the restoration of blood perfusion, however, its pathogenesis is not clear yet (Hausenloy and Yellon, 2013). Studies showed that cell apoptosis, mitochondrial dysfunction and increased production of oxygen free radicals are closely related to cardiomyocytes injury in the development of I/R, and are also important factors leading to aggravation of myocardial tissue injury (Lesnefsky et al., 2017). Therefore, relieving myocardial I/R injury and suppressing apoptosis of cardiomyocytes cells during hypoxia/reoxygenation (H/R) process have become a new challenge in the study of IHD.
Coptisine is an effective component of the perennial herb Coptis chinensis in Ranunculaceae, and its molecular formula is C19H14NO4. The extract, which is cold-natured and bitter in taste, can clear away heat and dampness in the body. Pathological study found that coptisine has many pharmacological effects such as anti-bacterial (Zhang et al., 2013), regulating cell proliferation (Shan et al., 2019), and improving inflammatory response (Hu et al., 2019). In previous studies, Feng M et al. (Feng et al., 2017) demonstrated that coptisine could ameliorate atherosclerosis and chronic inflammatory diseases through its anti-inflammatory and lipid-lowering effects. Moreover, it has been reported that coptisine had a vasorelaxant effect on aortic rings of rats (Gong et al., 2012). In the field of malignant tumors, coptisine inhibits the activity of human liver cancer cells and induces apoptosis via controlling the 67-kda laminin receptor (67LR)/cyclic guanosine 3′,5′-monophosphate (cGMP) pathway (Zhou et al., 2018). However, systematic reports on the role of coptisine in myocardial I/R injury are less conducted, thus, it is interesting to determine whether coptisine relieves I/R-induced cardiac injury.
In the present study, cardiomyocyte injury was induced by H/R and used to establish I/R-treated rat models, which were pre-treated by coptisine. The effects of coptisine on treating myocardial injury were detected by evaluating cell proliferation, apoptosis and pathological changes of cardiac tissues. The current study aimed to explore the action and mechanism of coptisine in myocardial damage induced by I/R and H/R, so as to explore a potential treatment for IHD.
Section snippets
Cell culture
Cardiomyocytes H9c2 cells were obtained from American Type Culture Collection (ATCC, Manassas, VA, USA) and cultured in high-glucose dulbecco's modified eagle medium (DMEM, Gibco, Carlsbad, CA, USA) containing 10 % fetal bovine serum (FBS, Gibco, USA) and 1% penicillin/streptomycin (Gibco, USA). The cells were cultured in a humid incubator at 37 °C with 5% CO2 for 24 h.
Hypoxia–reoxygenation (H/R)
The original medium was replaced by glucose-free medium to simulate ischemia to establish hypoxia–reoxygenation injury. The
The time of reoxygenation for H/R injury of cardiomyocytes was determined
According to the results of CCK-8 assay, the cell proliferation ability of H9c2 cardiomyocytes was reduced by approximately 5% after hypoxia induction for 6 h, and was further reduced by reoxygenation in a time-dependent manner (0, 3, 6, 9, 12, 15, 18, 21 and 24 h) (P < 0.05, Fig. 1). The reoxygenating time of 6 h, being the first reduction of significant difference (P < 0.01), was chosen for following experimens. As shown in Fig. 2A, there was no obvious change in the cell proliferation of
Discussion
Myocardial I/R injury critically affects the therapeutic effects of reperfusion on IDH patients (Perricone and Vander Heide, 2014). In the course of I/R, increased production of oxygen free radical is closely related to the apoptosis and injury of cardiomyocytes (Granger and Kvietys, 2015). As an effective component of coptis chinensis, coptisine is rich in resources and has a wide range of pharmacological effects on the treatment of various diseases, such as diabetes (Shi et al., 2019),
Conclusions
In conclusion, coptisine had protective effects on I/R-induced myocardial damage in vivo and in vitro through regulating the expressions of apoptotic proteins. The current findings may provide new understandings on the clinical treatment of I/R.
Author statement
Shengmei Sun designed the research study. Pengfei Wang performed the research. Shengmei Sun and Pengfei Wang analyzed the data. Shengmei Sun wrote the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Acknowledgements
Not applicable.
References (37)
- et al.
Anti-inflammatory activity of coptisine free base in mice through inhibition of NF-kappaB and MAPK signaling pathways
Eur. J. Pharmacol.
(2017) - et al.
The E3 Ubiquitin Ligase SCF(Cyclin F) Transmits AKT Signaling to the Cell-Cycle Machinery
Cell Rep.
(2017) - et al.
Sex differences in mechanisms, presentation and management of ischaemic heart disease
Atherosclerosis
(2015) - et al.
The epidemic of the 20(th) century: coronary heart disease
Am. J. Med.
(2014) BCL-2 proteins and apoptosis: recent insights and unknowns
Biochem. Biophys. Res. Commun.
(2018)- et al.
The protective effect of coptisine on experimental atherosclerosis ApoE(-/-) mice is mediated by MAPK/NF-kappaB-dependent pathway
Biomed. Pharmacother.
(2017) - et al.
Reperfusion injury and reactive oxygen species: the evolution of a concept
Redox Biol.
(2015) - et al.
Coptisine protects rat heart against myocardial ischemia/reperfusion injury by suppressing myocardial apoptosis and inflammation
Atherosclerosis
(2013) - et al.
Activation of Akt and JNK/Nrf2/NQO1 pathway contributes to the protective effect of coptisine against AAPH-induced oxidative stress
Biomed. Pharmacother.
(2017) - et al.
Corin protects H2O2-induced apoptosis through PI3K/AKT and NF-kappaB pathway in cardiomyocytes
Biomed. Pharmacother.
(2018)
Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method
Methods
Protective effect of coptisine free base on indomethacin-induced gastric ulcers in rats: characterization of potential molecular mechanisms
Life Sci.
BAX to basics: how the BCL2 gene family controls the death of retinal ganglion cells
Prog. Retin. Eye Res.
Novel therapeutic strategies for ischemic heart disease
Pharmacol. Res.
Glucose consumption assay discovers coptisine with beneficial effect on diabetic mice
Eur. J. Pharmacol.
Coptisine protects cardiomyocyte against hypoxia/reoxygenation-induced damage via inhibition of autophagy
Biochem. Biophys. Res. Commun.
Coptisine suppresses proliferation and inhibits metastasis in human pancreatic cancer PANC-1 cells
J. Asian Nat. Prod. Res.
MicroRNA-34a regulates cardiac ageing and function
Nature
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These authors contributed equally to this work.