Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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

The Protective of Baicalin on Myocardial Ischemia-Reperfusion Injury

Author(s): Xiaoli Liu, Shanshan Zhang, Chaoyue Xu, Yongchao Sun, Shujian Sui, Zhaohua Zhang* and Yun Luan*

Volume 21, Issue 13, 2020

Page: [1386 - 1393] Pages: 8

DOI: 10.2174/1389201021666200605104540

Price: $65

Abstract

Background: The aim of this study was to explore the inhibitory effect of baicalin on myocardial apoptosis induced by Ischemia-Reperfusion (I/R).

Methods: Sprague Dawley rats' heart and myocardial cells I/R model were established in vivo and vitro, then 100 mg/kg and 10 μmol/l baicalin were administrated, respectively. The experiment was randomly divided into 4 groups (n=10): Control; I/R; IR+DMEM; and I/R+baicalin groups. Postoperation, the Left Ventricular (LV) End-Diastolic Pressure (LVEDP), the maximum velocity of LV contraction (dP/dtmax) and the maximum velocity of LV diastole (dP/dtmin) were recorded by the transthoracic echocardiography; the myocardial apoptosis percentage was analyzed by Annexin VFITC/ PI and TUNEL staining, and the apoptosis gene and protein were detected by RT-PCR and western blot. Furthermore, the protein expression of the calcium-sensing receptor (CaSR) and ERK1/2 phosphorylation were observed by western blot and Fura-2-acetoxymethyl ester. Moreover, primary rats’ cardiomyocytes were cultured and ERK1/2 specific inhibitor PD98059 was added to the culture medium. The cell survival rate, vitality and apoptosis were detected by MTT, lactate dehydrogenase (LDH) and TUNEL staining assay Kit, respectively.

Results: Our present study showed that baicalin significantly improved LV hemodynamic parameters and myocardial apoptosis in myocardial I/R injury rats. Furthermore, we found that baicalin could down-regulate the protein expression of CaSR, but up-regulate the protein expression of ERK1/2. Furthermore, when the cells were pretreated with ERK1/2 inhibitor PD98059, the cells survival rate significantly decreased, but LDH activity and apoptosis significantly increased. The results indicated that the effect of baicalin on myocardial I/R injury could be inhibited by ERK1/2 inhibitor.

Conclusion: In conclusion, our data suggests that baicalin attenuates I/R-induced myocardial injury maybe through the suppression of the CaSR/ERK1/2 signaling pathway.

Keywords: Baicalin, cardiomyocytes, I/R, apoptosis, CaSR, myocardial apoptosis.

« Previous Next »
Graphical Abstract

[1]
Li, B.Q.; Fu, T.; Dongyan, Y.; Mikovits, J.A.; Ruscetti, F.W.; Wang, J.M. Flavonoid baicalin inhibits HIV-1 infection at the level of viral entry. Biochem. Biophys. Res. Commun., 2000, 276(2), 534-538.
[http://dx.doi.org/10.1006/bbrc.2000.3485] [PMID: 11027509]
[2]
Chou, T.C.; Chang, L.P.; Li, C.Y.; Wong, C.S.; Yang, S.P. The antiinflammatory and analgesic effects of baicalin in carrageenan-evoked thermal hyperalgesia. Anesth. Analg., 2003, 97(6), 1724-1729.
[http://dx.doi.org/10.1213/01.ANE.0000087066.71572.3F] [PMID: 14633550]
[3]
Zhang, Xiping; Hua, Tian Chen, H. The protecting effects and mechanisms of baicalin and octreotide on heart injury in rats with SAP. Mediators Inflame., 2007, 12(3), 19469-19480.
[4]
Woo, A.Y.; Cheng, C.H.; Waye, M.M. Baicalein protects rat cardiomyocytes from hypoxia/reoxygenation damage via a prooxidant mechanism. Cardiovasc. Res., 2005, 65(1), 244-253.
[http://dx.doi.org/10.1016/j.cardiores.2004.09.027] [PMID: 15621053]
[5]
Lin, L.; Wu, X.D.; Davey, A.K.; Wang, J. The anti-inflammatory effect of baicalin on hypoxia/reoxygenation and TNF-α induced injury in cultural rat cardiomyocytes. Phytother. Res., 2010, 24(3), 429-437.
[http://dx.doi.org/10.1002/ptr.3003] [PMID: 19827018]
[6]
Kang, P.M.; Izumo, S. Apoptosis in heart: Basic mechanisms and implications in cardiovascular diseases. Trends Mol. Med., 2003, 9(4), 177-182.
[http://dx.doi.org/10.1016/S1471-4914(03)00025-X] [PMID: 12727144]
[7]
Kim, N.H.; Kang, P.M. Apoptosis in cardiovascular diseases: mechanism and clinical implications. Korean Circ. J., 2010, 40(7), 299-305.
[http://dx.doi.org/10.4070/kcj.2010.40.7.299] [PMID: 20664736]
[8]
Wang, Y.L.; Wang, C.Y.; Zhang, B.J.; Zhang, Z.Z. Shenfu injection suppresses apoptosis by regulation of Bcl-2 and caspase-3 during hypoxia/reoxygenation in neonatal rat cardiomyocytes in vitro. Mol. Biol. Rep., 2009, 36(2), 365-370.
[http://dx.doi.org/10.1007/s11033-007-9188-x] [PMID: 18049909]
[9]
Eefting, F.; Rensing, B.; Wigman, J. Role of apoptosis in reperfusion injury. Cardiovasc. Res., 2004, 61(3), 414-426.
[http://dx.doi.org/10.1016/j.cardiores.2003.12.023]
[10]
Dumont, EA.; Hofstra, L.; van Heerde, WL. Cardiomyocyte death induced by myocardial ischemia and reperfusion: Measurement with recombinant human Annexin-V in a mouse model. Circulation, 2000, 102(3), 1564-1568.
[http://dx.doi.org/10.1161/01.CIR.102.13.1564]
[11]
Hofstra, L.; Liem, I.H.; Dumont, E.A.; Boersma, H.H.; van Heerde, W.L.; Doevendans, P.A.; De Muinck, E.; Wellens, H.J.; Kemerink, G.J.; Reutelingsperger, C.P.; Heidendal, G.A. Visualisation of cell death in vivo in patients with acute myocardial infarction. Lancet, 2000, 356(9225), 209-212.
[http://dx.doi.org/10.1016/S0140-6736(00)02482-X] [PMID: 10963199]
[12]
Borutaite, V.; Jekabsone, A.; Morkuniene, R.; Brown, G.C. Inhibition of mitochondrial permeability transition prevents mitochondrial dysfunction, cytochrome C release and apoptosis induced by heart ischemia. J. Mol. Cell. Cardiol., 2003, 35(4), 357-366.
[http://dx.doi.org/10.1016/S0022-2828(03)00005-1 ] [PMID: 12689815]
[13]
Chung, Y.C.; Lim, J.H.; Oh, H.M.; Kim, H.W.; Kim, M.Y.; Kim, E.N.; Kim, Y.; Chang, Y.S.; Kim, H.W.; Park, C.W. Calcimimetic restores diabetic peripheral neuropathy by ameliorating apoptosis and improving autophagy. Cell Death Dis., 2018, 9(12), 1163.
[http://dx.doi.org/10.1038/s41419-018-1192-7] [PMID: 30478254]
[14]
Yan, L.; Zhu, T.; Sun, T.; Wang, L.; Pan, S.; Tao, Z.; Yang, Z.; Cao, K. Activation of calcium-sensing receptors is associated with apoptosis in a model of simulated cardiomyocytes ischemia/reperfusion. J. Biomed. Res., 2010, 24(4), 301-307.
[http://dx.doi.org/10.1016/S1674-8301(10)60042-5 ] [PMID: 23554644]
[15]
Lu, M.; Leng, B.; He, X.; Zhang, Z.; Wang, H.; Tang, F. Calcium sensing receptor-related pathway contributes to cardiac injury and the mechanism of astragaloside IV on cardioprotection. Front. Pharmacol., 2018, 9, 1163.
[http://dx.doi.org/10.3389/fphar.2018.01163] [PMID: 30364197]
[16]
Gan, R.; Hu, G.; Zhao, Y.; Li, H.; Jin, Z.; Ren, H.; Dong, S.; Zhong, X.; Li, H.; Yang, B.; Xu, C.; Lu, F.; Zhang, W. Post-conditioning protecting rat cardiomyocytes from apoptosis via attenuating calcium-sensing receptor-induced endo(sarco)plasmic reticulum stress. Mol. Cell. Biochem., 2012, 361(1-2), 123-134.
[http://dx.doi.org/10.1007/s11010-011-1096-7] [PMID: 21984037]
[17]
Shao, Z.; Bhattacharya, K.; Hsich, E.; Park, L.; Walters, B.; Germann, U.; Wang, Y.M.; Kyriakis, J.; Mohanlal, R.; Kuida, K.; Namchuk, M.; Salituro, F.; Yao, Y.M.; Hou, W.M.; Chen, X.; Aronovitz, M.; Tsichlis, P.N.; Bhattacharya, S.; Force, T.; Kilter, H. cJun N-terminal kinases mediate reactivation of Akt and cardiomyocyte survival after hypoxic injury in vitro and in vivo. Circ. Res, 2006, 98(1), 111-118.
[http://dx.doi.org/10.1161/01.RES.0000197781.20524.b9] [PMID: 16306447]
[18]
Luan, Y.; Sun, C.; Wang, J.; Jiang, W.; Xin, Q.; Zhang, Z.; Wang, Y. Baicalin attenuates myocardial ischemia-reperfusion injury through Akt/NF-κB pathway. J. Cell. Biochem., 2019, 120(3), 3212-3219.
[http://dx.doi.org/10.1002/jcb.27587] [PMID: 30242878]
[19]
Ou, Y.; Dong, X.; Liu, X.Y.; Cheng, X.C.; Cheng, Y.N.; Yu, L.G.; Guo, X.L. Mechanism of tetramethylpyrazine analogue CXC195 inhibition of hydrogen peroxide-induced apoptosis in human endothelial cells. Biol. Pharm. Bull., 2010, 33(3), 432-438.
[http://dx.doi.org/10.1248/bpb.33.432] [PMID: 20190405]
[20]
Ivanova, T.N.; Alonso-Gomez, A.L.; Iuvone, P.M. Dopamine D4 receptors regulate intracellular calcium concentration in cultured chicken cone photoreceptor cells: Relationship to dopamine receptor-mediated inhibition of cAMP formation. Brain Res., 2008, 1207(5), 111-119.
[http://dx.doi.org/10.1016/j.brainres.2008.02.025] [PMID: 18371938]
[21]
Rizzuto, R.; Duchen, M.R.; Pozzan, T. Flirting in little space: the ER/mitochondria Ca2+ liaison. Sci. STKE, 2004, 2004(215), re1.
[PMID: 14722345]
[22]
Xu, C.; Bailly-Maitre, B.; Reed, J.C. Endoplasmic reticulum stress: cell life and death decisions. J. Clin. Invest., 2005, 115(10), 2656-2664.
[http://dx.doi.org/10.1172/JCI26373] [PMID: 16200199]
[23]
Choi, S.E.; Kim, H.E.; Shin, H.C.; Jang, H.J.; Lee, K.W.; Kim, Y.; Kang, S.S.; Chun, J.; Kang, Y. Involvement of Ca2+-mediated apoptotic signals in palmitate-induced MIN6N8a beta cell death. Mol. Cell. Endocrinol., 2007, 272(1-2), 50-62.
[http://dx.doi.org/10.1016/j.mce.2007.04.004] [PMID: 17507155]
[24]
Lu, F.; Tian, Z.; Zhang, W.; Zhao, Y.; Bai, S.; Ren, H.; Chen, H.; Yu, X.; Wang, J.; Wang, L.; Li, H.; Pan, Z.; Tian, Y.; Yang, B.; Wang, R.; Xu, C. Calcium-sensing receptors induce apoptosis in rat cardiomyocytes via the endo(sarco)plasmic reticulum pathway during hypoxia/reoxygenation. Basic Clin. Pharmacol. Toxicol., 2010, 106(5), 396-405.
[PMID: 20030631]
[25]
Kim, H.S.; Chang, W.C.; Hwang, K.C.; Choi, I.G.; Park, W.K. Effect of propofol on calcium homeostasis in hypoxia-reoxygenated neonatal rat cardiomyocytes. Eur. J. Pharmacol., 2008, 594(1-3), 139-145.
[http://dx.doi.org/10.1016/j.ejphar.2008.07.027] [PMID: 18674530]
[26]
Woo, A.Y.; Waye, M.M.; Tsui, S.K.; Yeung, S.T.; Cheng, C.H. Andrographolide up-regulates cellular-reduced glutathione level and protects cardiomyocytes against hypoxia/reoxygenation injury. J. Pharmacol. Exp. Ther., 2008, 325(1), 226-235.
[http://dx.doi.org/10.1124/jpet.107.133918] [PMID: 18174384]
[27]
Shao, Z.H.; Vanden Hoek, T.L.; Qin, Y.; Becker, L.B.; Schumacker, P.T.; Li, C.Q.; Dey, L.; Barth, E.; Halpern, H.; Rosen, G.M.; Yuan, C.S. Baicalein attenuates oxidant stress in cardiomyocytes. Am. J. Physiol. Heart Circ. Physiol., 2002, 282(3), H999-H1006.
[http://dx.doi.org/10.1152/ajpheart.00163.2001] [PMID: 11834498]
[28]
Zhang, Z.; Yu, B.; Tao, G.Z. Apelin protects against cardiomyocyte apoptosis induced by glucose deprivation. Chin. Med. J. (Engl.), 2009, 122(19), 2360-2365.
[PMID: 20079140]
[29]
Mani, K. Programmed cell death in cardiac myocytes: strategies to maximize post-ischemic salvage. Heart Fail. Rev., 2008, 13(2), 193-209.
[http://dx.doi.org/10.1007/s10741-007-9073-7] [PMID: 18176842]
[30]
Bers, D.M. Calcium and cardiac rhythms: Physiological and pathophysiological. Circ. Res., 2002, 90(1), 14-17.
[http://dx.doi.org/10.1161/res.90.1.14] [PMID: 11786512]
[31]
Gu, J.; Dai, S.; Liu, Y.; Liu, H.; Zhang, Y.; Ji, X.; Yu, F.; Zhou, Y.; Chen, L.; Tse, W.K.F.; Wong, C.K.C.; Chen, B.; Shi, H. Activation of Ca2+-sensing receptor as a protective pathway to reduce Cadmium-induced cytotoxicity in renal proximal tubular cells. Sci. Rep., 2018, 8(1), 1092.
[http://dx.doi.org/10.1038/s41598-018-19327-9] [PMID: 29348484]
[32]
Kabir, M.E.; Singh, H.; Lu, R.; Olde, B.; Leeb-Lundberg, L.M.; Bopassa, J.C.G.G. Protein-coupled estrogen receptor 1 mediates acute estrogen-induced cardioprotection via MEK/ERK/GSK-3β pathway after ischemia/reperfusion. PLoS One, 2015, 10(9)e0135988
[http://dx.doi.org/10.1371/journal.pone.0135988] [PMID: 26356837]
[33]
Filippone, S.M.; Samidurai, A.; Roh, S.K.; Cain, C.K.; He, J.; Salloum, F.N.; Kukreja, R.C.; Das, A. Reperfusion therapy with rapamycin attenuates myocardial infarction through activation of AKT and ERK. Oxid. Med. Cell. Longev., 2017, 20174619720
[http://dx.doi.org/10.1155/2017/4619720] [PMID: 28373901]

Rights & Permissions Print Cite
Article Metrics
23
1
© 2024 Bentham Science Publishers | Privacy Policy