{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T05:08:25Z","timestamp":1777439305236,"version":"3.51.4"},"reference-count":61,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,9,20]],"date-time":"2018-09-20T00:00:00Z","timestamp":1537401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research Project of Education Department of Liaoning Province","award":["L2017lkyfwdf-05"],"award-info":[{"award-number":["L2017lkyfwdf-05"]}]},{"name":"Public Welfare Fund Project of Department of Science and Technology of Liaoning Province","award":["2016003003"],"award-info":[{"award-number":["2016003003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Trichosanthis Pericarpium (TP) is a traditional Chinese medicine for treating cardiovascular diseases. In this study, we investigated the effects of TP aqueous extract (TPAE) on hypoxia\/reoxygenation (H\/R) induced injury in H9c2 cardiomyocytes and explored the underlying mechanisms. H9c2 cells were cultured under the hypoxia condition induced by sodium hydrosulfite for 30 min and reoxygenated for 4 h. Cell viability was measured by MTT assay. The amounts of LDH, NO, eNOS, and iNOS were tested by ELISA kits. Apoptotic rate was detected by Annexin V-FITC\/PI staining. QRT-PCR was performed to analyze the relative mRNA expression of Akt, Bcl-2, Bax, eNOS, and iNOS. Western blotting was used to detect the expression of key members in the PI3K\/Akt pathway. Results showed that the pretreatment of TPAE remarkably enhanced cell viability and decreased apoptosis induced by H\/R. Moreover, TPAE decreased the release of LDH and expression of iNOS. In addition, TPAE increased NO production and Bcl-2\/Bax ratio. Furthermore, the mRNA and protein expression of p-Akt and eNOS were activated by TPAE pretreatment. On the contrary, a specific inhibitor of PI3K, LY294002 not only inhibited TPAE-induced p-Akt\/eNOS upregulation but alleviated its anti-apoptotic effects. In conclusion, results indicated that TPAE protected against H\/R injury in cardiomyocytes, which consequently activated the PI3K\/Akt\/NO signaling pathway.<\/jats:p>","DOI":"10.3390\/molecules23102409","type":"journal-article","created":{"date-parts":[[2018,9,21]],"date-time":"2018-09-21T03:46:35Z","timestamp":1537501595000},"page":"2409","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Trichosanthis Pericarpium Aqueous Extract Protects H9c2 Cardiomyocytes from Hypoxia\/Reoxygenation Injury by Regulating PI3K\/Akt\/NO Pathway"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8988-6885","authenticated-orcid":false,"given":"Donghai","family":"Chu","sequence":"first","affiliation":[{"name":"Liaoning University of Traditional Chinese Medicine, No. 77 Shengming 1st Road, Dalian 11600, Liaoning, China"},{"name":"Liaoning Institute of Science and Technology, No. 76 Xianghuai Road, Benxi 117004, Liaoning, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenqiu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Liaoning University of Traditional Chinese Medicine, No. 77 Shengming 1st Road, Dalian 11600, Liaoning, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Huang, X., Zuo, L., Lv, Y., Chen, C., Yang, Y., Xin, H., Li, Y., and Qian, Y. (2016). Asiatic Acid Attenuates Myocardial Ischemia\/Reperfusion Injury via Akt\/GSK-3beta\/HIF-1alpha Signaling in Rat H9c2 Cardiomyocytes. Molecules, 21.","DOI":"10.3390\/molecules21091248"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1161\/hc4601.099487","article-title":"Global burden of cardiovascular diseases: Part I: General considerations, the epidemiologic transition, risk factors, and impact of urbanization","volume":"104","author":"Yusuf","year":"2001","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.carpath.2005.03.006","article-title":"Myocardial ischemia and reperfusion injury","volume":"14","author":"Buja","year":"2005","journal-title":"Cardiovasc. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Gao, L.N., Zhou, X., Zhang, Y., Cui, Y.L., Yu, C.Q., and Gao, S. (2015). The anti-inflammatory activities of ethanol extract from Dan-Lou prescription in vivo and in vitro. BMC Complement. Altern. Med., 15.","DOI":"10.1186\/s12906-015-0848-4"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0254-6272(17)30020-1","article-title":"Gualoupi (Pericarpium Trichosanthis) injection in combination with convention therapy for the treatment of angina pectoris: A Meta-analysis","volume":"37","author":"Zhu","year":"2017","journal-title":"J. Tradit. Chin. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Liao, P., Sun, G., Zhang, C., Wang, M., Sun, Y., Zhou, Y., Sun, X., and Jian, J. (2016). Bauhinia championii Flavone Attenuates Hypoxia-Reoxygenation Induced Apoptosis in H9c2 Cardiomyocytes by Improving Mitochondrial Dysfunction. Molecules, 21.","DOI":"10.3390\/molecules21111469"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1172\/JCI62874","article-title":"Myocardial ischemia-reperfusion injury: A neglected therapeutic target","volume":"123","author":"Hausenloy","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Qi, J.Y., Wang, L., Gu, D.S., Guo, L.H., Zhu, W., and Zhang, M.Z. (2016). Protect effects of Danlou Tablet against murine myocardial ischemia and reperfusion injury in vivo. Chin. J. Integr. Med.","DOI":"10.1007\/s11655-016-2448-7"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ding, Y.F., Peng, Y.R., Shen, H., Shu, L., and Wei, Y.J. (2016). Gualou Xiebai decoction inhibits cardiac dysfunction and inflammation in cardiac fibrosis rats. BMC Complement. Altern. Med., 16.","DOI":"10.1186\/s12906-016-1012-5"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hu, F., Koon, C.M., Chan, J.Y., Lau, K.M., and Fung, K.P. (2012). The cardioprotective effect of danshen and gegen decoction on rat hearts and cardiomyocytes with post-ischemia reperfusion injury. BMC Complement. Altern. Med., 12.","DOI":"10.1186\/1472-6882-12-249"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mao, S., Wang, L., Ouyang, W., Zhou, Y., Qi, J., Guo, L., Zhang, M., and Hinek, A. (2016). Traditional Chinese medicine, Danlou tablets alleviate adverse left ventricular remodeling after myocardial infarction: Results of a double-blind, randomized, placebo-controlled, pilot study. BMC Complement. Altern. Med., 16.","DOI":"10.1186\/s12906-016-1406-4"},{"key":"ref_12","unstructured":"Chinese Pharmacopoeia Commission (2015). Pharmacopoeia of the People\u2019s Republic of China, China Medical Science and Technology Press. [10th ed.]."},{"key":"ref_13","first-page":"17106","article-title":"Protective effects of Trichosanthes on cardiovascular system","volume":"9","author":"Li","year":"2016","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.3389\/fphys.2017.01132","article-title":"Trichosanthes pericarpium Aqueous Extract Enhances the Mobilization of Endothelial Progenitor Cells and Up-regulates the Expression of VEGF, eNOS, NO, and MMP-9 in Acute Myocardial Ischemic Rats","volume":"8","author":"Fu","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.phymed.2018.01.004","article-title":"Protective effects of total flavonoids from Clinopodium chinense (Benth.) O. Ktze on myocardial injury in vivo and in vitro via regulation of Akt\/Nrf2\/HO-1 pathway","volume":"40","author":"Zhang","year":"2018","journal-title":"Phytomedicine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.fitote.2014.06.014","article-title":"The protective effects of Schisandra chinensis fruit extract and its lignans against cardiovascular disease: A review of the molecular mechanisms","volume":"97","author":"Chun","year":"2014","journal-title":"Fitoterapia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1080\/08941930701366471","article-title":"Akt in ischemia and reperfusion","volume":"20","author":"Mullonkal","year":"2007","journal-title":"J. Investig. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.tcm.2005.03.001","article-title":"The reperfusion injury salvage kinase pathway: A common target for both ischemic preconditioning and postconditioning","volume":"15","author":"Hausenloy","year":"2005","journal-title":"Trends Cardiovas. Med."},{"key":"ref_19","first-page":"593","article-title":"Cardioprotective effect of breviscapine: Inhibition of apoptosis in H9c2 cardiomyocytes via the PI3K\/Akt\/eNOS pathway following simulated ischemia\/reperfusion injury","volume":"70","author":"Wang","year":"2015","journal-title":"Pharmazie"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1055\/s-0030-1271019","article-title":"Andrographolide inhibits PI3K\/AKT-dependent NOX2 and iNOS expression protecting mice against hypoxia\/ischemia-induced oxidative brain injury","volume":"77","author":"Chern","year":"2011","journal-title":"Planta Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9727","DOI":"10.1523\/JNEUROSCI.0879-12.2012","article-title":"Endothelial cell-derived nitric oxide enhances aerobic glycolysis in astrocytes via HIF-1alpha-mediated target gene activation","volume":"32","author":"Brix","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1111\/bph.12993","article-title":"FM19G11 reverses endothelial dysfunction in rat and human arteries through stimulation of the PI3K\/Akt\/eNOS pathway, independently of mTOR\/HIF-1alpha activation","volume":"172","author":"El","year":"2015","journal-title":"Brit. J. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"L996","DOI":"10.1152\/ajplung.00276.2013","article-title":"Genistein attenuates hypoxic pulmonary hypertension via enhanced nitric oxide signaling and the erythropoietin system","volume":"306","author":"Kuriyama","year":"2014","journal-title":"Am. J. Physiol. Lung. C."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1159\/000110027","article-title":"Inducible Nitric Oxide Synthase Mediates Hypoxia-Induced Hypoxia-Inducible Factor-1\u03b1 Activation and Vascular Endothelial Growth Factor Expression in Oxygen-Induced Retinopathy","volume":"74","author":"He","year":"2007","journal-title":"Pathobiology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/aps.2016.14","article-title":"Methylophiopogonanone A suppresses ischemia\/reperfusion-induced myocardial apoptosis in mice via activating PI3K\/Akt\/eNOS signaling pathway","volume":"37","author":"He","year":"2016","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ejphar.2015.10.046","article-title":"Cardio-protective effects of combined l-arginine and insulin: Mechanism and therapeutic actions in myocardial ischemia-reperfusion injury","volume":"769","author":"Venardos","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.1161\/01.CIR.101.23.2742","article-title":"Attenuation of myocardial ischemia\/reperfusion injury by superinduction of inducible nitric oxide synthase","volume":"101","author":"Kanno","year":"2000","journal-title":"Circulation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1161\/01.RES.87.3.241","article-title":"Peroxynitrite is a major contributor to cytokine-induced myocardial contractile failure","volume":"87","author":"Ferdinandy","year":"2000","journal-title":"Circ. Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Li, J., Loukili, N., Rosenblatt-Velin, N., Pacher, P., Feihl, F., Waeber, B., and Liaudet, L. (2013). Peroxynitrite is a key mediator of the cardioprotection afforded by ischemic postconditioning in vivo. PLoS ONE, 8.","DOI":"10.1371\/annotation\/4cf3075f-3090-44d7-aa9e-8a927ed9d5fa"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1172\/JCI986","article-title":"Role of nitric oxide and peroxynitrite in the cytokine-induced sustained myocardial dysfunction in dogs in vivo","volume":"101","author":"Oyama","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_31","first-page":"H509","article-title":"Mechanisms of cardioprotection by peroxynitrite in myocardial ischemia and reperfusion injury","volume":"275","author":"Nossuli","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/S0008-6363(00)00078-X","article-title":"Status of myocardial antioxidants in ischemia-reperfusion injury","volume":"47","author":"Dhalla","year":"2000","journal-title":"Cardiovasc. Res."},{"key":"ref_33","first-page":"L976","article-title":"Sodium hydrosulfite contractions of smooth muscle are calcium and myosin phosphorylation independent","volume":"275","author":"Yu","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1152\/jappl.1965.20.5.912","article-title":"Effect of temperature on deoxygenation rate of human red cells","volume":"20","author":"Lawson","year":"1965","journal-title":"J. Appl. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.3892\/mmr.2014.2016","article-title":"Effects of hypoxia on progranulin expression in HT22 mouse hippocampal cells","volume":"9","author":"Luo","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.brainres.2014.09.039","article-title":"Neuroprotective effects of gallic acid against hypoxia\/reoxygenation-induced mitochondrial dysfunctions in vitro and cerebral ischemia\/reperfusion injury in vivo","volume":"1589","author":"Sun","year":"2014","journal-title":"Brain Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/S0006-8993(98)01249-9","article-title":"Effects of hypoxia induced by Na2S2O4 on intracellular calcium and resting potential of mouse glomus cells","volume":"818","author":"Zhang","year":"1999","journal-title":"Brain Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1161\/ATVBAHA.111.224915","article-title":"Mechanisms of cell death in heart disease","volume":"32","author":"Konstantinidis","year":"2012","journal-title":"Arterioscler. Throm. Vas."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zhang, B., Chen, Y., Shen, Q., Liu, G., Ye, J., Sun, G., and Sun, X. (2016). Myricitrin Attenuates High Glucose-Induced Apoptosis through Activating Akt-Nrf2 Signaling in H9c2 Cardiomyocytes. Molecules, 21.","DOI":"10.3390\/molecules21070880"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/j.1365-2362.1991.tb01383.x","article-title":"Endogenous nitric oxide: Physiology, pathology and clinical relevance","volume":"21","author":"Moncada","year":"1991","journal-title":"Eur. J. Clin. Invest."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1016\/j.bbagen.2012.08.014","article-title":"Novel aminobenzyl-acetamidine derivative modulate the differential regulation of NOSs in LPS induced inflammatory response: Role of PI3K\/Akt pathway","volume":"1820","author":"Patruno","year":"2012","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s11239-013-0944-6","article-title":"EPC mobilization after erythropoietin treatment in acute ST-elevation myocardial infarction: The REVEAL EPC substudy","volume":"36","author":"Povsic","year":"2013","journal-title":"J. Thromb. Thrombolys."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.toxlet.2012.11.023","article-title":"Cardioprotective effect of salvianolic acid B against arsenic trioxide-induced injury in cardiac H9c2 cells via the PI3K\/Akt signal pathway","volume":"216","author":"Wang","year":"2013","journal-title":"Toxicol. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/0092-8674(93)90509-O","article-title":"Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death","volume":"74","author":"Oltvai","year":"1993","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4053","DOI":"10.1242\/jcs.00754","article-title":"The Bcl-2-regulated apoptotic pathway","volume":"116","author":"Willis","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nrm2308","article-title":"The BCL-2 protein family: Opposing activities that mediate cell death","volume":"9","author":"Youle","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1182\/blood-2002-06-1714","article-title":"Amount of spontaneous apoptosis detected by Bax\/Bcl-2 ratio predicts outcome in acute myeloid leukemia (AML)","volume":"101","author":"Del","year":"2003","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/nature04869","article-title":"Ras, PI(3)K and mTOR signalling controls tumour cell growth","volume":"441","author":"Shaw","year":"2006","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.fct.2013.11.013","article-title":"Taxifolin prevents diabetic cardiomyopathy in vivo and in vitro by inhibition of oxidative stress and cell apoptosis","volume":"63","author":"Sun","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Gu, S., Zhang, W., Chen, J., Ma, R., Xiao, X., Ma, X., Yao, Z., and Chen, Y. (2014). EPC-derived microvesicles protect cardiomyocytes from Ang II-induced hypertrophy and apoptosis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085396"},{"key":"ref_51","first-page":"1123","article-title":"Synthesis of 2-amino-4, 5-diarylpyrimidines and their protective effects against oxygen-glucose deprivation in PC12 cells","volume":"45","author":"Gao","year":"2010","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s11010-016-2658-5","article-title":"PI3K\/Akt\/FoxO3a signaling mediates cardioprotection of FGF-2 against hydrogen peroxide-induced apoptosis in H9c2 cells","volume":"414","author":"Liu","year":"2016","journal-title":"Mol. Cell. Biochem."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Kanazawa, H., Imoto, K., Okada, M., and Yamawaki, H. (2017). Canstatin inhibits hypoxia-induced apoptosis through activation of integrin\/focal adhesion kinase\/Akt signaling pathway in H9c2 cardiomyoblasts. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0173051"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Chen, H.M., Hsu, J.H., Liou, S.F., Chen, T.J., Chen, L.Y., Chiu, C.C., and Yeh, J.L. (2014). Baicalein, an active component of Scutellaria baicalensis Georgi, prevents lysophosphatidylcholine-induced cardiac injury by reducing reactive oxygen species production, calcium overload and apoptosis via MAPK pathways. BMC Complement. Altern. Med., 14.","DOI":"10.1186\/1472-6882-14-233"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1159\/000445634","article-title":"Geniposide Prevents Hypoxia\/Reoxygenation-Induced Apoptosis in H9c2 Cells: Improvement of Mitochondrial Dysfunction and Activation of GLP-1R and the PI3K\/AKT Signaling Pathway","volume":"39","author":"Jiang","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Pooja, S., Pushpanathan, M., Gunasekaran, P., and Rajendhran, J. (2015). Endocytosis-Mediated Invasion and Pathogenicity of Streptococcus agalactiae in Rat Cardiomyocyte (H9C2). PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0139733"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1159\/000477597","article-title":"Protective Effects of MicroRNA-126 on Human Cardiac Microvascular Endothelial Cells Against Hypoxia\/Reoxygenation-Induced Injury and Inflammatory Response by Activating PI3K\/Akt\/eNOS Signaling Pathway","volume":"42","author":"Yang","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Mei, X., Wang, H.X., Li, J.S., Liu, X.H., Lu, X.F., Li, Y., Zhang, W.Y., and Tian, Y.G. (2017). Dusuqing granules (DSQ) suppress inflammation in Klebsiella pneumonia rat via NF-\u03baB\/MAPK signaling. BMC Complement. Altern. Med., 17.","DOI":"10.1186\/s12906-017-1736-x"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Sun, S., Yang, S., Dai, M., Jia, X., Wang, Q., Zhang, Z., and Mao, Y. (2017). The effect of Astragalus polysaccharides on attenuation of diabetic cardiomyopathy through inhibiting the extrinsic and intrinsic apoptotic pathways in high glucose -stimulated H9C2 cells. BMC Complement. Altern. Med., 17.","DOI":"10.1186\/s12906-017-1828-7"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1161\/ATVBAHA.109.189480","article-title":"Nrf2 protects against maladaptive cardiac responses to hemodynamic stress","volume":"29","author":"Li","year":"2009","journal-title":"Arterioscler. Throm. Vas."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3758","DOI":"10.3390\/molecules20033758","article-title":"Tyrosol prevents ischemia\/reperfusion-induced cardiac injury in H9c2 cells: Involvement of ROS, Hsp70, JNK and ERK, and apoptosis","volume":"20","author":"Sun","year":"2015","journal-title":"Molecules"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/10\/2409\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:21:35Z","timestamp":1760196095000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/10\/2409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,20]]},"references-count":61,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2018,10]]}},"alternative-id":["molecules23102409"],"URL":"https:\/\/doi.org\/10.3390\/molecules23102409","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,20]]}}}