{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:55:00Z","timestamp":1787028900995,"version":"build-2736575974"},"reference-count":68,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:00:00Z","timestamp":1637712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Key Research and Development Program of China","award":["2018YFD0901102"],"award-info":[{"award-number":["2018YFD0901102"]}]},{"name":"the Special Funds of Fujian Ocean and Fisheries Structure Adjustment","award":["2020HYJG06"],"award-info":[{"award-number":["2020HYJG06"]}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22078120"],"award-info":[{"award-number":["22078120"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Major Science and Technology Special Project of Fujian Province","award":["2020NZ012013"],"award-info":[{"award-number":["2020NZ012013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Angiotensin-I-converting enzyme (ACE) is a crucial enzyme or receptor that catalyzes the generation of potent vasopressor angiotensin II (Ang II). ACE inhibitory peptides from fish showed effective ACE inhibitory activity. In this study, we reported an ACE inhibitory peptide from Takifugu bimaculatus (T. bimaculatus), which was obtained by molecular docking with acid-soluble collagen (ASC) hydrolysate of T. bimaculatus. The antihypertensive effects and potential mechanism were conducted using Ang-II-induced human umbilical vein endothelial cells (HUVECs) as a model. The results showed that FNLRMQ alleviated the viability and facilitated apoptosis of Ang-II-induced HUVECs. Further research suggested that FNLRMQ may protect Ang-II-induced endothelial injury by regulating Nrf2\/HO-1 and PI3K\/Akt\/eNOS signaling pathways. This study, herein, reveals that collagen peptide FNLRMQ could be used as a potential candidate compound for antihypertensive treatment, and could provide scientific evidence for the high-value utilization of marine resources including T. bimaculatus.<\/jats:p>","DOI":"10.3390\/md19120655","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T01:43:22Z","timestamp":1638323002000},"page":"655","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["ACE Inhibitory Peptide from Skin Collagen Hydrolysate of Takifugu bimaculatus as Potential for Protecting HUVECs Injury"],"prefix":"10.3390","volume":"19","author":[{"given":"Shuilin","family":"Cai","sequence":"first","affiliation":[{"name":"College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"},{"name":"Key Laboratory of Cultivation and High-value Utilization of Marine Organisms in Fujian Province, Fisheries Research Institute of Fujian, Xiamen 361013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6182-6058","authenticated-orcid":false,"given":"Nan","family":"Pan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cultivation and High-value Utilization of Marine Organisms in Fujian Province, Fisheries Research Institute of Fujian, Xiamen 361013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cultivation and High-value Utilization of Marine Organisms in Fujian Province, Fisheries Research Institute of Fujian, Xiamen 361013, China"},{"name":"College of Food and Biological Engineering, Jimei University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongchang","family":"Su","sequence":"additional","affiliation":[{"name":"College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"},{"name":"Key Laboratory of Cultivation and High-value Utilization of Marine Organisms in Fujian Province, Fisheries Research Institute of Fujian, Xiamen 361013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2372-2837","authenticated-orcid":false,"given":"Kun","family":"Qiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cultivation and High-value Utilization of Marine Organisms in Fujian Province, Fisheries Research Institute of Fujian, Xiamen 361013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cultivation and High-value Utilization of Marine Organisms in Fujian Province, Fisheries Research Institute of Fujian, Xiamen 361013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9548-1457","authenticated-orcid":false,"given":"Bingde","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meitian","family":"Xiao","sequence":"additional","affiliation":[{"name":"College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cultivation and High-value Utilization of Marine Organisms in Fujian Province, Fisheries Research Institute of Fujian, Xiamen 361013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1007\/s11906-010-0150-2","article-title":"Vascular endothelial function and hypertension: Insights and directions","volume":"12","author":"Dharmashankar","year":"2010","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/hr.2011.39","article-title":"Oxidative stress and endothelial dysfunction in hypertension","volume":"34","author":"Schulz","year":"2011","journal-title":"Hypertens. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1161\/01.CIR.0000131515.03336.f8","article-title":"Role of endothelial dysfunction in atherosclerosis","volume":"109","author":"Davignon","year":"2004","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1017\/S0954422413000139","article-title":"The impact of milk proteins and peptides on blood pressure and vascular function: A review of evidence from human intervention studies","volume":"26","author":"Fekete","year":"2013","journal-title":"Nutr. Res. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1080\/07853890701854702","article-title":"Pathophysiology, diagnosis and prognostic implications of endothelial dysfunction","volume":"40","author":"Munzel","year":"2008","journal-title":"Ann. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1038\/sj.jhh.1001889","article-title":"Targeting endothelial dysfunction in hypertensive subjects","volume":"19","author":"Thuillez","year":"2005","journal-title":"J. Hum. Hypertens."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S314","DOI":"10.2337\/dc09-S330","article-title":"Endothelial Dysfunction as a Target for Prevention of Cardiovascular Disease","volume":"32","author":"Versari","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.3346\/jkms.2015.30.9.1213","article-title":"Endothelial dysfunction: Clinical implications in cardiovascular disease and therapeutic approaches","volume":"30","author":"Park","year":"2015","journal-title":"J. Korean Med. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/S0735-1097(03)00994-X","article-title":"The clinical implications of endothelial dysfunction","volume":"42","author":"Widlansky","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"R83","DOI":"10.1530\/JOE-14-0662","article-title":"The role of Nrf2 in oxidative stress-induced endothelial injuries","volume":"225","author":"Chen","year":"2015","journal-title":"J. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1161\/01.RES.81.6.970","article-title":"Angiotensin II induces apoptosis of human endothelial cells\u2014Protective effect of nitric oxide","volume":"81","author":"Dimmeler","year":"1997","journal-title":"Circ. Res."},{"key":"ref_12","first-page":"273","article-title":"Regulation of apoptosis by angiotensin II in the heart and lungs (review)","volume":"7","author":"Filippatos","year":"2001","journal-title":"Int. J. Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhang, L.Q., Wang, J.J., Liang, J.Q., Feng, D., Deng, F., Yang, Y., Lu, Y., and Hu, Z. (2018). Propofol prevents human umbilical vein endothelial cell injury from Ang II-induced apoptosis by activating the ACE2-(1-7)-Mas axis and eNOS phosphorylation. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199373"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"682041","DOI":"10.1155\/2014\/682041","article-title":"Alpha-asarone protects endothelial cells from injury by angiotensin II","volume":"2014","author":"Shi","year":"2014","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1177\/0960327119893414","article-title":"Sulforaphane attenuates angiotensin II-induced human umbilical vein endothelial cell injury by modulating ROS-mediated mitochondrial signaling","volume":"39","author":"Zhang","year":"2020","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"A31","DOI":"10.1016\/S1520-765X(03)90061-7","article-title":"Angiotensin-converting enzyme inhibition and endothelial dysfunction: Focus on ramipril","volume":"5","author":"Enseleit","year":"2003","journal-title":"Eur. Heart J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s10557-007-6041-3","article-title":"ACE inhibition and endothelial function: Main findings of PERFECT, a sub-study of the EUROPA trial","volume":"21","author":"Bots","year":"2007","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"H1425","DOI":"10.1152\/ajpheart.00783.2003","article-title":"ACE inhibitors and statins acutely improve endothelial dysfunction of human coronary arterioles","volume":"286","author":"Tiefenbacher","year":"2004","journal-title":"Am. J. Physiol. Heart Circ."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14","DOI":"10.5090\/kjtcs.2013.46.1.14","article-title":"Antioxidant effect of captopril and enalapril on reactive oxygen species-induced endothelial dysfunction in the rabbit abdominal aorta","volume":"46","author":"Kim","year":"2013","journal-title":"Korean J. Thorac. Cardiovasc. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1111\/j.1524-6175.2004.02866.x","article-title":"Angiotensin-converting enzyme inhibitors side effects--physiologic and non-physiologic considerations","volume":"6","author":"Sica","year":"2004","journal-title":"J. Clin. Hypertens."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1271\/bbb.100560","article-title":"Effect of an excess intake of casein hydrolysate containing Val-Pro-Pro and Ile-Pro-Pro in subjects with normal blood pressure, high-normal blood pressure, or mild hypertension","volume":"75","author":"Ishida","year":"2011","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.bbagen.2017.08.014","article-title":"Marine natural product peptides with therapeutic potential: Chemistry, biosynthesis, and pharmacology","volume":"1862","author":"Gogineni","year":"2018","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ovchinnikova, T.V. (2019). Structure, Function, and therapeutic potential of marine bioactive peptides. Mar. Drugs, 17.","DOI":"10.3390\/md17090505"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Pujiastuti, D.Y., Amin, M.N.G., Alamsjah, M.A., and Hsu, J.L. (2019). Marine organisms as potential sources of bioactive peptides that inhibit the activity of angiotensin i-converting enzyme: A review. Molecules, 24.","DOI":"10.3390\/molecules24142541"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s41240-019-0125-4","article-title":"Biological activity of peptides purified from fish skin hydrolysates","volume":"22","author":"Abuine","year":"2019","journal-title":"Fish. Aquat. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.tifs.2016.01.019","article-title":"Marine bioactive compounds and health promoting perspectives; innovation pathways for drug discovery","volume":"50","author":"Suleria","year":"2016","journal-title":"Trends Food Sci. Technol."},{"key":"ref_27","first-page":"2148","article-title":"Tetrodotoxin detection and species identification of pufferfish in retail roasted fish fillet by DNA barcoding in China","volume":"32","author":"Li","year":"2015","journal-title":"Food Addit. Contam. Part A"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100315","DOI":"10.1016\/j.scp.2020.100315","article-title":"Collagen extraction and recent biological activities of collagen peptides derived from sea-food waste: A review","volume":"18","author":"Ahmed","year":"2020","journal-title":"Sustain. Chem. Pharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1111\/j.1365-2109.2010.02707.x","article-title":"Toxicity of cultured puffer fish and seasonal variations in China","volume":"42","author":"Ji","year":"2011","journal-title":"Aquac. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/s10126-019-09938-2","article-title":"Construction of a high-density genetic linkage map and qtl mapping for growth-related traits in Takifugu bimaculatus","volume":"22","author":"Shi","year":"2020","journal-title":"Mar. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e9655","DOI":"10.7717\/peerj.9655","article-title":"Characterization of two myostatin genes in pufferfish Takifugu bimaculatus: Sequence, genomic structure, and expression","volume":"8","author":"Sheng","year":"2020","journal-title":"PeerJ"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/B978-0-12-416003-3.00016-0","article-title":"Marine fish-derived bioactive peptides as potential antihypertensive agents","volume":"65","author":"Kim","year":"2012","journal-title":"Adv. Food Nutr. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1146\/annurev-food-022814-015520","article-title":"Antihypertensive peptides from food proteins","volume":"6","author":"Aluko","year":"2015","journal-title":"Annu. Rev. Food Sci. Technol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1161\/01.HYP.21.6.921","article-title":"Captopril inhibits endothelin-1 secretion from endothelial cells through bradykinin","volume":"21","author":"Momose","year":"1993","journal-title":"Hypertension"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1097\/00005344-200111002-00007","article-title":"Endothelium and atherogenesis: Endothelial therapy revisited","volume":"38","author":"Barton","year":"2001","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1161\/01.HYP.0000153321.13792.b9","article-title":"Angiotensin II and the endothelium-diverse signals and effects","volume":"45","author":"Watanabe","year":"2005","journal-title":"Hypertension"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"34","DOI":"10.5494\/wjh.v2.i4.34","article-title":"Oxidative stress-mediated effects of angiotensin II in the cardiovascular system","volume":"2","author":"Wen","year":"2012","journal-title":"World J. Hypertens."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.cellimm.2009.09.006","article-title":"The ACE inhibitors enalapril and captopril modulate cytokine responses in Balb\/c and C57Bl\/6 normal mice and increase CD4(+)CD103(+)CD25(negative) splenic T cell numbers","volume":"260","author":"Albuquerque","year":"2010","journal-title":"Cell. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"152","DOI":"10.5114\/aoms.2018.74026","article-title":"Renin-angiotensin system inhibitor attenuates oxidative stress induced human coronary artery endothelial cell dysfunction via the PI3K\/AKT\/mTOR pathway","volume":"15","author":"Shi","year":"2019","journal-title":"Arch. Med. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.cca.2005.07.021","article-title":"Angiotensin converting enzyme inhibitor attenuates oxidative stress-induced endothelial cell apoptosis via p38 MAP kinase inhibition","volume":"364","author":"Yu","year":"2006","journal-title":"Clin. Chim. Acta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4411","DOI":"10.1021\/acs.jafc.0c00925","article-title":"Mechanism analysis of a novel angiotensin-I-converting enzyme inhibitory peptide from isochrysis zhanjiangensis microalgae for suppressing vascular injury in human umbilical vein endothelial cells","volume":"68","author":"Chen","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_42","first-page":"69","article-title":"Is Bax\/Bcl-2 ratio considered as a prognostic marker with age and tumor location in colorectal cancer?","volume":"19","author":"Khodapasand","year":"2015","journal-title":"Iran. Biomed. J."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Shao, W.J., Yu, Z.W., Chiang, Y.T., Yang, Y., Chai, T.Y., Foltz, W., Lu, H.G., Fantus, I.G., and Jin, T.R. (2012). Curcumin prevents high fat diet induced insulin resistance and obesity via attenuating lipogenesis in liver and inflammatory pathway in adipocytes. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0028784"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.3389\/fphys.2018.01668","article-title":"Vascular oxidative stress: Impact and therapeutic approaches","volume":"9","author":"Sena","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Dayem, A.A., Hossain, M.K., Lee, S.B., Kim, K., Saha, S.K., Yang, G.M., Choi, H.Y., and Cho, S.G. (2017). The role of reactive oxygen species (ROS) in the biological activities of metallic nanoparticles. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18010120"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3164734","DOI":"10.1155\/2016\/3164734","article-title":"The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults","volume":"2016","author":"Nita","year":"2016","journal-title":"Oxidative Med. Cell."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1097\/FJC.0b013e3181e5f2e2","article-title":"Atorvastatin protects against angiotensin II-induced injury and dysfunction in human umbilical vein endothelial cells through Bradykinin 2 receptors","volume":"56","author":"Zhang","year":"2010","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Chen, J., Gong, F., Chen, M.F., Li, C., Hong, P., Sun, S., Zhou, C., and Qian, Z.J. (2019). In vitro vascular-protective effects of a tilapia by-product oligopeptide on angiotensin II-induced hypertensive endothelial injury in HUVEC by Nrf2\/NF-\u03baB pathways. Mar. Drugs, 17.","DOI":"10.3390\/md17070431"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.atherosclerosis.2014.09.001","article-title":"Vascular oxidative stress, nitric oxide and atherosclerosis","volume":"237","author":"Li","year":"2014","journal-title":"Atherosclerosis"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1161\/CIRCRESAHA.116.309326","article-title":"Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis","volume":"120","author":"Forstermann","year":"2017","journal-title":"Circ. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1159\/000479873","article-title":"Epigallocatechin-3-gallate ameliorates angiotensin II-induced oxidative stress and apoptosis in human umbilical vein endothelial cells through the activation of Nrf2\/Caspase-3 signaling","volume":"54","author":"Zhou","year":"2017","journal-title":"J. Vasc. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"172516","DOI":"10.1016\/j.ejphar.2019.172516","article-title":"SIRT6 protects vascular endothelial cells from angiotensin II-induced apoptosis and oxidative stress by promoting the activation of Nrf2\/ARE signaling","volume":"859","author":"Yang","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"382","DOI":"10.3389\/fphar.2019.00382","article-title":"Nrf2 as a potential mediator of cardiovascular risk in metabolic diseases","volume":"10","author":"Rodrigues","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"H425","DOI":"10.1152\/ajpheart.00689.2008","article-title":"Vascular endothelial dysfunction with aging: Endothelin-1 and endothelial nitric oxide synthase","volume":"297","author":"Donato","year":"2009","journal-title":"Am. J. Physiol. Heart Circ."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"R1288","DOI":"10.1152\/ajpregu.00397.2010","article-title":"The interaction between endothelin-1 and nitric oxide in the vasculature: New perspectives","volume":"300","author":"Bourque","year":"2011","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1093\/cvr\/cvt065","article-title":"Angiotensin (17) counteracts the negative effect of angiotensin II on insulin signalling in HUVECs","volume":"99","author":"Tassone","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"118","DOI":"10.2337\/db06-0288","article-title":"Attenuation of angiotensin II signaling recouples eNOS and inhibits nonendothelial NOX activity in diabetic mice","volume":"56","author":"Oak","year":"2007","journal-title":"Diabetes"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1161\/CIRCULATIONAHA.105.602532","article-title":"Endothelial nitric oxide synthase in vascular disease: From marvel to menace","volume":"113","author":"Forstermann","year":"2006","journal-title":"Circulation"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/21218","article-title":"Regulation of endothelium-derived nitric oxide production by the protein kinase Akt","volume":"399","author":"Fulton","year":"1999","journal-title":"Nature"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.phymed.2018.05.005","article-title":"Lespedeza cuneata protects the endothelial dysfunction via eNOS phosphorylation of PI3K\/Akt signaling pathway in HUVECs","volume":"48","author":"Lee","year":"2018","journal-title":"Phytomedicine"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6255","DOI":"10.3892\/mmr.2017.7328","article-title":"Hydrogen sulfide facilities production of nitric oxide via the Akt\/endothelial nitric oxide synthases signaling pathway to protect human umbilical vein endothelial cells from injury by angiotensin II","volume":"16","author":"Cui","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.bbalip.2014.12.006","article-title":"PI3K signalling in inflammation","volume":"1851","author":"Hawkins","year":"2015","journal-title":"Biochim.-Mol. Cell Biol. Lipids"},{"key":"ref_63","first-page":"6595189","article-title":"Hypoxia-activated PI3K\/Akt inhibits oxidative stress via the regulation of reactive oxygen species in human dental pulp cells","volume":"2019","author":"Liu","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/s41419-019-1696-9","article-title":"FGF1(Delta HBS) ameliorates chronic kidney disease via PI3K\/AKT mediated suppression of oxidative stress and inflammation","volume":"10","author":"Wang","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4536","DOI":"10.1074\/jbc.M207293200","article-title":"Increased protein stability as a mechanism that enhances Nrf2-mediated transcriptional activation of the antioxidant response element\u2014Degradation of Nrf2 by the 26 S proteasome","volume":"278","author":"Nguyen","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_66","first-page":"8112","article-title":"PI3K\/AKT signaling pathway plays a role in enhancement of eNOS activity by recombinant human angiotensin converting enzyme 2 in human umbilical vein endothelial cells","volume":"7","author":"Zhang","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Attique, S.A., Hassan, M., Usman, M., Atif, R.M., Mahboob, S., Al-Ghanim, K.A., Bilal, M., and Nawaz, M.Z. (2019). A Molecular docking approach to evaluate the pharmacological properties of natural and synthetic treatment candidates for use against hypertension. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16060923"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.3389\/fphar.2018.01579","article-title":"Three novel ACE inhibitory peptides isolated from ginkgo biloba seeds: Purification, inhibitory kinetic and mechanism","volume":"9","author":"Ma","year":"2019","journal-title":"Front. Pharmacol."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/19\/12\/655\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:35:15Z","timestamp":1760168115000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/19\/12\/655"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,24]]},"references-count":68,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["md19120655"],"URL":"https:\/\/doi.org\/10.3390\/md19120655","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,24]]}}}