Effect of astragaloside IV against rat myocardial cell apoptosis induced by oxidative stress via mitochondrial ATP-sensitive potassium channels

Guan,Feng‑Ying; Yang,Shi‑Jie; Liu,Jinxiang; Yang,Si‑Rui

doi:10.3892/mmr.2015.3400

Effect of astragaloside IV against rat myocardial cell apoptosis induced by oxidative stress via mitochondrial ATP-sensitive potassium channels

Authors:
- Feng‑Ying Guan
- Shi‑Jie Yang
- Jinxiang Liu
- Si‑Rui Yang
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Affiliations: Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Pediatric Cardiology, Institute of Pediatrics, The First Affiliated Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: February 27, 2015 https://doi.org/10.3892/mmr.2015.3400
Pages: 371-376

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Abstract

Astragaloside is one of the most common traditional Chinese medicines and is derived from Astragalus membranaceus. Astragaloside IV (AsIV) is a monomer located in an extract of astragaloside. The current study investigated the protective effects of AsIV against hydrogen peroxide (H2O2)‑induced injury in cardiocytes and elucidated the mechanisms responsible for this protective effect. Cultured neonatal rat cardiocytes were divided into five experimental groups as follows: i) Dimethyl sulfoxide; ii) H2O2; iii) AsIV+H2O2; iv) AsIV+H2O2+5‑hydroxydecanoate (5‑HD); and v) nicorandil+H2O2. Cardiocyte survival was analyzed using an MTT assay. Lactate dehydrogenase (LDH) release was also assessed to evaluate the viability of the cells. Intracellular reactive oxygen species (ROS) were measured by 2,7‑dichlorodihydrofluorescein diacetate staining. The apoptotic rate was measured by flow cytometry. Mitochondrial membrane potential (ΔΨm) and intracellular calcium were observed using a laser confocal microscopy system. The results indicated that AsIV promoted the survival of cardiocytes (P<0.05), attenuated LDH release (P<0.05), ROS production (P<0.01) and apoptosis (P<0.01), stabilized the ΔΨm and reduced intracellular calcium overload (P<0.01) compared with the H2O2 group. The mitochondrial adenosine triphosphate‑sensitive potassium channel (mitoKATP) inhibitor 5‑HD was observed to partially reverse the protective effect of AsIV. Following treatment with 5‑HD, the survival of cardiocytes was reduced (P<0.05), LDH release (P<0.01) and ROS production (P<0.05) were stimulated, ΔΨm and intracellular calcium change were increased (P<0.01) and apoptosis was increased (P<0.01) compared with the AsIV+H2O2 group. Thus, AsIV has potential for use in the suppression of apoptosis resulting from H2O2 exposure, and mitoKATP activation may underlie this protective mechanism.

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1	Murphy E and Steenbergen C: Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol Rev. 88:581–609. 2008. View Article : Google Scholar : PubMed/NCBI
2	Paradies G, Petrosillo G, Pistolese M, Di Venosa N, Federici A and Ruggiero FM: Decrease in mitochondrial complex I activity in ischemic/reperfused rat heart: involvement of reactive oxygen species and cardiolipin. Circ Res. 94:53–59. 2004. View Article : Google Scholar
3	Lemasters JJ, Theruvath TP, Zhong Z and Nieminen AL: Mitochondrial calcium and the permeability transition in cell death. Biochim Biophys Acta. 1787:1395–1401. 2009. View Article : Google Scholar : PubMed/NCBI
4	Baines CP: The mitochondrial permeability transition pore and ischemia-reperfusion injury. Basic Res Cardiol. 104:181–188. 2009. View Article : Google Scholar : PubMed/NCBI
5	Weiss JN, Korge P, Honda HM and Ping P: Role of the mitochondrial permeability transition in myocardial disease. Circ Res. 93:292–301. 2003. View Article : Google Scholar : PubMed/NCBI
6	Fryer RM, Eells JT, Hsu AK, Henry MM and Gross GJ: Ischemic preconditioning in rats: role of mitochondrial K(ATP) channel in preservation of mitochondrial function. Am J Physiol Heart Circ Physiol. 278:H305–H312. 2000.PubMed/NCBI
7	Garlid KD and Halestrap AP: The mitochondrial K(ATP) channel-fact or fiction? J Mol Cell Cardiol. 52:578–583. 2012. View Article : Google Scholar : PubMed/NCBI
8	Wakiyama H, Cowan DB, Toyoda Y, Federman M, Levitsky S and McCully JD: Selective opening of mitochondrial ATP-sensitive potassium channels during surgically induced myocardial ischemia decreases necrosis and apoptosis. Eur J Cardiothorac Surg. 21:424–433. 2002. View Article : Google Scholar : PubMed/NCBI
9	Zhou JY, Fan Y, Kong JL, Wu DZ and Hu ZB: Effects of components isolated from Astragalus membranaceus Bunge on cardiac function injured by myocardial ischemia reperfusion in rats. Zhongguo Zhong Yao Za Zhi. 300–302. 2000.In Chinese.
10	Xu YC, Lan SL and Chen JY: Effects of huangqi sijun decoction on thyroxin and cyclic nucleotide levels in rat models with spleen deficiency syndrome. Chin Drug Res Clin Pharm. 18:291–293. 2007.
11	Guan FY and Yu XX: The protective effect of Astragalus membranaceus injection preconditioning on experimental myocardial ischemia/reperfusion injury in rats. Chin J Geront. 30:3126–3129. 2010.
12	Yang J, Li J, Lu J, Zhang Y, Zhu Z and Wan H: Synergistic protective effect of astragaloside IV-tetramethylpyrazine against cerebral ischemic-reperfusion injury induced by transient focal ischemia. J Ethnopharmacol. 140:64–72. 2012. View Article : Google Scholar
13	Meng LQ, Tang JW, Wang Y, et al: Astragaloside IV synergizes with ferulic acid to inhibit renal tubulointerstitial fibrosis in rats with obstructive nephropathy. Br J Pharmacol. 162:1805–1818. 2011. View Article : Google Scholar : PubMed/NCBI
14	Xie W and Du L: Diabetes is an inflammatory disease: evidence from traditional Chinese medicines. Diabetes Obes Metab. 13:289–301. 2011. View Article : Google Scholar : PubMed/NCBI
15	Qiu LH, Xie XJ and Zhang BQ: Astragaloside IV improves homocysteine-induced acute phase endothelial dysfunction via antioxidation. Biol Pharm Bull. 33:641–646. 2010. View Article : Google Scholar : PubMed/NCBI
16	Zhao Z, Wang W, Wang F, et al: Effects of Astragaloside IV on heart failure in rats. Chin Med. 4:62009. View Article : Google Scholar : PubMed/NCBI
17	Guan FY, Li H, Sun W and Yang SJ: Protective effects of Astragaloside IV on hydrogen peroxide-induced injury of cultured neonatal rat myocardial cells. J Jilin Uni Med Ed. 33:211–214. 2007.
18	Zhang WD, Chen H, Zhang C, Liu RH, Li HL and Chen HZ: Astragaloside IV from Astragalus membranaceus shows cardio-protection during myocardial ischemia in vivo and in vitro. Planta Med. 72:4–8. 2006. View Article : Google Scholar : PubMed/NCBI
19	Xu XL, Chen XJ, Ji H, et al: Astragaloside IV improved intracellular calcium handling in hypoxia-reoxygenated cardiocytes via the sarcoplasmic reticulum Ca-ATPase. Pharmacology. 81:325–332. 2008. View Article : Google Scholar
20	Yu WP, Xu GL, Shen CX and Qian ZY: Effects of crocetin on the apoptosis and the changes of its related regulating proteins caspase-3 and Bcl-2 induced by H₂O₂ in myocardial cell. Chin J Pathoph. 22:54–57. 2006.
21	Smith MA and Schnellmann RG: Calpains, mitochondria and apoptosis. Cardiovasc Res. 96:32–37. 2012. View Article : Google Scholar : PubMed/NCBI
22	Grivicich I, Regner A, da Rocha AB, et al: Irinotecan/5-fluorouracil combination induces alterations in mitochondrial membrane potential and caspases on colon cancer cell lines. Oncol Res. 15:385–392. 2005.
23	Kallio A, Zheng A, Dahllund J, Heiskanen KM and Harkonen P: Role of mitochondria in tamoxifen-induced rapid death of MCF-7 breast cancer cells. Apoptosis. 10:1395–1410. 2005. View Article : Google Scholar : PubMed/NCBI
24	Shrivastava A, Tiwari M, Sinha RA, et al: Molecular iodine induces caspase-independent apoptosis in human breast carcinoma cells involving the mitochondria-mediated pathway. J Biol Chem. 281:19762–19771. 2006. View Article : Google Scholar : PubMed/NCBI
25	Shi LG, Zhang GP and Jin HM: Inhibition of microvascular endothelial cell apoptosis by angiopoietin-1 and the involvement of cytochrome C. Chin Med J (Engl). 119:725–730. 2006.
26	Murata M, Akao M, O’Rourke B and Marban E: Mitochondrial ATP-sensitive potassium channels attenuate matrix Ca(2+) overload during simulated ischemia and reperfusion: possible mechanism of cardioprotection. Circ Res. 89:891–898. 2001. View Article : Google Scholar : PubMed/NCBI
27	Shahid M, Tauseef M, Sharma KK and Fahim M: Brief femoral artery ischaemia provides protection against myocardial ischaemia-reperfusion injury in rats: the possible mechanisms. Exp Physiol. 93:954–968. 2008. View Article : Google Scholar : PubMed/NCBI
28	Wu Q, Bie P, Tang C and Zhang YJ: An experiment study on the role of bcl-2 in attenuation ischemia-reperfusion injury in liver graft in mice induced by mitoKATP channel opener diazoxide. J Clin Med Practi. 12:35–40. 2008.
29	Tratsiakovich Y, Gonon AT, Krook A, et al: Arginase inhibition reduces infarct size via nitric oxide, protein kinase C epsilon and mitochondrial ATP-dependent K⁺ channels. Eur J Pharmacol. 712:16–21. 2013. View Article : Google Scholar : PubMed/NCBI
30	Soeding PF, Crack PJ, Wright CE, Angus JA and Royse CF: Levosimendan preserves the contractile responsiveness of hypoxic human myocardium via mitochondrial K(ATP) channel and potential pERK 1/2 activation. Eur J Pharmacol. 655:59–66. 2011. View Article : Google Scholar : PubMed/NCBI