{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:20:34Z","timestamp":1790619634680,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Taishan Industrial Leading Talents Project-Blue Talent Special and Qingdao key technology research and industrialization demonstration projects","award":["22-3-3-hygg-5-hy"],"award-info":[{"award-number":["22-3-3-hygg-5-hy"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Hypertension is a common disease that affects human health and can lead to damage to the heart, kidneys, and other important organs. In this study, we investigated the regulatory effects of bioactive peptides derived from Ruditapes philippinarum (RPP) on hypertension and organ protection in deoxycorticosterone acetate (DOCA)\u2013salt hypertensive rats. We found that RPPs exhibited significant blood pressure-lowering properties. Furthermore, the results showed that RPPs positively influenced vascular remodeling and effectively maintained a balanced water\u2013sodium equilibrium. Meanwhile, RPPs demonstrated anti-inflammatory potential by reducing the serum levels of inflammatory cytokines (TNF-\u03b1, IL-2, and IL-6). Moreover, we observed the strong antioxidant activity of RPPs, which played a critical role in reducing oxidative stress and alleviating hypertension-induced damage to the aorta, heart, and kidneys. Additionally, our study explored the regulatory effects of RPPs on the gut microbiota, suggesting a possible correlation between their antihypertensive effects and the modulation of gut microbiota. Our previous studies have demonstrated that RPPs can significantly reduce blood pressure in SHR rats. This suggests that RPPs can significantly improve both essential hypertension and DOAC\u2013salt-induced secondary hypertension and can ameliorate cardiorenal damage caused by hypertension. These findings further support the possibility of RPPs as an active ingredient in functional anti-hypertensive foods.<\/jats:p>","DOI":"10.3390\/molecules28227610","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T01:56:29Z","timestamp":1700099789000},"page":"7610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Bioactive Peptides from Ruditapes philippinarum Attenuate Hypertension and Cardiorenal Damage in Deoxycorticosterone Acetate\u2013Salt Hypertensive Rats"],"prefix":"10.3390","volume":"28","author":[{"given":"Zonghui","family":"Sun","sequence":"first","affiliation":[{"name":"College of Life Sciences, Qingdao University, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixia","family":"Wang","sequence":"additional","affiliation":[{"name":"Qingdao Chenlan Pharmaceutical Co., Ltd., Qingdao 266061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinli","family":"Liu","sequence":"additional","affiliation":[{"name":"Qingdao Chenlan Pharmaceutical Co., Ltd., Qingdao 266061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengcan","family":"Zou","sequence":"additional","affiliation":[{"name":"Qingdao Chenlan Pharmaceutical Co., Ltd., Qingdao 266061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongli","family":"Yin","sequence":"additional","affiliation":[{"name":"Qingdao Chenlan Pharmaceutical Co., Ltd., Qingdao 266061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghan","family":"Lyu","sequence":"additional","affiliation":[{"name":"Qingdao Chenlan Pharmaceutical Co., Ltd., Qingdao 266061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8366-2960","authenticated-orcid":false,"given":"Jia","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Qingdao University, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0616-479X","authenticated-orcid":false,"given":"Yuxi","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Qingdao University, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"key":"ref_1","first-page":"453","article-title":"Secondary Hypertension: Discovering the Underlying Cause","volume":"96","author":"Charles","year":"2017","journal-title":"Am. Fam. Physician"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s11906-020-01091-9","article-title":"The Gut Microbiome, Inflammation, and Salt-Sensitive Hypertension","volume":"22","author":"Elijovich","year":"2020","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s11906-019-0948-5","article-title":"The Influence of Dietary Salt Beyond Blood Pressure","volume":"21","author":"Robinson","year":"2019","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.cnc.2015.08.003","article-title":"Hypertensive Crisis: A Review of Pathophysiology and Treatment","volume":"27","author":"Taylor","year":"2015","journal-title":"Crit. Care Nurs. Clin. N. Am."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"77","DOI":"10.2165\/00129784-200202020-00002","article-title":"Antihypertensive Drugs: An Overview","volume":"2","author":"Ram","year":"2002","journal-title":"Am. J. Cardiovasc. Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"n189","DOI":"10.1136\/bmj.n189","article-title":"Association between Antihypertensive Treatment and Adverse Events: Systematic Review and Meta-Analysis","volume":"372","author":"Albasri","year":"2021","journal-title":"BMJ"},{"key":"ref_7","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_8","doi-asserted-by":"crossref","unstructured":"Qin, N., Chen, C., Zhang, N., Song, L., Li, Y., Guo, L., Liu, R., and Zhang, W. (2023). Bitter Almond Albumin Ace-Inhibitory Peptides: Purification, Screening, and Characterization in Silico, Action Mechanisms, Antihypertensive Effect in Vivo, and Stability. Molecules, 28.","DOI":"10.3390\/molecules28166002"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Baskaran, R., Balasubramanian, B., Ho, J.H., Wang, M.F., Abomughaid, M.M., Yang, H.S., and Lin, W.T. (2022). Vh-4-a Bioactive Peptide from Soybean and Exercise Training Constrict Hypertension in Rats through Activating Cell Survival and Ampk\u03b11, Sirt1, Pgc1\u03b1, and Fox3\u03b1. Molecules, 27.","DOI":"10.3390\/molecules27227705"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1016\/j.isci.2019.08.049","article-title":"Clam Genome Sequence Clarifies the Molecular Basis of Its Benthic Adaptation and Extraordinary Shell Color Diversity","volume":"19","author":"Yan","year":"2019","journal-title":"iScience"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1007\/s13197-020-04796-6","article-title":"Evaluation indicators of Ruditapes philippinarum nutritional quality","volume":"58","author":"Chen","year":"2021","journal-title":"J. Food Sci. Technol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.fsi.2018.06.019","article-title":"A Defensin-Like Antimicrobial Peptide from the Manila Clam Ruditapes Philippinarum: Investigation of the Antibacterial Activities and Mode of Action","volume":"80","author":"Yang","year":"2018","journal-title":"Fish Shellfish Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Song, Y., Cai, Q., Wang, S., Li, L., Wang, Y., Zou, S., Gao, X., and Wei, Y. (2022). The Ameliorative Effect and Mechanisms of Ruditapes philippinarum Bioactive Peptides on Obesity and Hyperlipidemia Induced by a High-Fat Diet in Mice. Nutrients, 14.","DOI":"10.3390\/nu14235066"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1021\/acs.jafc.0c04232","article-title":"Identification and Antihypertension Study of Novel Angiotensin I-Converting Enzyme Inhibitory Peptides from the Skirt of Chlamys farreri Fermented with Bacillus natto","volume":"69","author":"Gao","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_15","first-page":"216","article-title":"Optimization of Enzymatic Hydrolysis of Hongdao Clam and Anti-Hypertensive Activity of the Resulted Products","volume":"42","author":"Cao","year":"2021","journal-title":"Sci. Technol. Food Ind."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1038\/s41401-022-01041-y","article-title":"GPR97 deficiency ameliorates renal interstitial fibrosis in mouse hypertensive nephropathy","volume":"44","author":"Wu","year":"2023","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/s10020-021-00408-x","article-title":"Fibroblast Growth Factor 21 Attenuates Salt-Sensitive Hypertension-Induced Nephropathy through Anti-Inflammation and Anti-Oxidation Mechanism","volume":"27","author":"Weng","year":"2021","journal-title":"Mol. Med."},{"key":"ref_18","first-page":"1841","article-title":"The criteria for the selection of antihypertensive drugs by JSH2014 guidelines","volume":"73","author":"Shimada","year":"2015","journal-title":"Nihon Rinsho"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1161\/HYPERTENSIONAHA.109.144840","article-title":"mPGES-1 Protects Against DOCA-Salt Hypertension via Inhibition of Oxidative Stress or Stimulation of NO\/cGMP","volume":"55","author":"Jia","year":"2010","journal-title":"Hypertension"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"868934","DOI":"10.3389\/fcvm.2022.868934","article-title":"Inflammatory Mediators in Atherosclerotic Vascular Remodeling","volume":"9","author":"Evans","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_21","first-page":"e133690","article-title":"Roxadustat prevents Ang II hypertension by targeting angiotensin receptors and eNOS","volume":"6","author":"Yu","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"16461","DOI":"10.1038\/s41598-019-52839-6","article-title":"Pioglitazone Modulates the Vascular Contractility in Hypertension by Interference with Et-1 Pathway","volume":"9","author":"Hernanz","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41440-021-00796-x","article-title":"Hypotensive Effect of Captopril on Deoxycorticosterone Acetate-Salt-Induced Hypertensive Rat Is Associated with Gut Microbiota Alteration","volume":"45","author":"Wu","year":"2022","journal-title":"Hypertens Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/hr.2010.236","article-title":"Aldosterone-to-renin ratio and home blood pressure in subjects with higher and lower sodium intake: The Ohasama Study","volume":"34","author":"Satoh","year":"2011","journal-title":"Hypertens. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1161\/HYPERTENSIONAHA.119.12762","article-title":"Renal Inflammation in Doca-Salt Hypertension","volume":"73","author":"Banek","year":"2019","journal-title":"Hypertension"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1111\/j.1440-1681.2010.05428.x","article-title":"Immunosuppression with mycophenolate mofetil attenuates the development of hypertension and albuminuria in deoxycorticosterone acetate-salt hypertensive rats","volume":"37","author":"Boesen","year":"2010","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1097\/01.mnh.0000435609.35789.32","article-title":"Corin: A New Player in the Regulation of Salt-Water Balance and Blood Pressure","volume":"22","author":"Armaly","year":"2013","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/ejhf.656","article-title":"Chronic heart failure as a state of reduced effectiveness of the natriuretic peptide system: Implications for therapy","volume":"19","year":"2017","journal-title":"Eur. J. Heart Fail."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/S0006-291X(05)80082-8","article-title":"Increased plasma brain natriuretic peptide levels in DOCA-salt hypertensive rats: Relation to blood pressure and cardiac concentration","volume":"173","author":"Yokota","year":"1990","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.jchf.2019.05.012","article-title":"Differential Regulation of ANP and BNP in Acute Decompensated Heart Failure: Deficiency of ANP","volume":"7","author":"Reginauld","year":"2019","journal-title":"JACC Heart Fail."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"107863","DOI":"10.1016\/j.pharmthera.2021.107863","article-title":"The natriuretic peptide system in heart failure: Diagnostic and therapeutic implications","volume":"227","author":"Kuwahara","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jfda.2019.11.002","article-title":"Bioactive peptides attenuate cardiac hypertrophy and fibrosis in spontaneously hypertensive rat hearts","volume":"28","author":"Huang","year":"2020","journal-title":"J. Food Drug Anal."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1080\/00015385.2019.1669847","article-title":"Sst2 Adds to the Prognostic Value of Gal-3 and Bnp in Chronic Heart Failure","volume":"75","author":"Barutaut","year":"2020","journal-title":"Acta Cardiol."},{"key":"ref_34","first-page":"778","article-title":"Relationship between arterial hypertension and renal damage in chronic kidney disease: Insights from ABPM","volume":"19","author":"Paoletti","year":"2006","journal-title":"J. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"R1229","DOI":"10.1152\/ajpregu.00720.2010","article-title":"Renal Oxidative Stress, Oxygenation, and Hypertension","volume":"301","author":"Palm","year":"2011","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"107035","DOI":"10.1016\/j.intimp.2020.107035","article-title":"Triptolide attenuates renal damage by limiting inflammatory responses in DOCA-salt hypertension","volume":"89","author":"Zhang","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1007\/s00726-021-03028-1","article-title":"Bioactive peptide apelin rescues acute kidney injury by protecting the function of renal tubular mitochondria","volume":"53","author":"Guan","year":"2021","journal-title":"Amino Acids"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1007\/s00467-018-4005-4","article-title":"Oxidative stress in chronic kidney disease","volume":"34","author":"Daenen","year":"2019","journal-title":"Pediatr. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2710","DOI":"10.1002\/jsfa.11611","article-title":"Effects of almonds on ameliorating salt-induced hypertension in dahl salt-sensitive rats","volume":"102","author":"Zeng","year":"2022","journal-title":"J. Sci. Food Agric."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1161\/HYPERTENSIONAHA.122.18556","article-title":"Gut-Immune-Kidney Axis: Influence of Dietary Protein in Salt-Sensitive Hypertension","volume":"79","author":"Mattson","year":"2022","journal-title":"Hypertension"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Cai, R., Hao, Y., Liu, Y.-Y., Huang, L., Yao, Y., and Zhou, M.-S. (2020). Tumor Necrosis Factor Alpha Deficiency Improves Endothelial Function and Cardiovascular Injury in Deoxycorticosterone Acetate\/Salt-Hypertensive Mice. BioMed Res. Int., 2020.","DOI":"10.1155\/2020\/3921074"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1152\/physiolgenomics.00136.2014","article-title":"Evidence for a link between gut microbiota and hypertension in the Dahl rat","volume":"47","author":"Mell","year":"2015","journal-title":"Physiol. Genom."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Rizzatti, G., Lopetuso, L.R., Gibiino, G., Binda, C., and Gasbarrini, A. (2017). Proteobacteria: A Common Factor in Human Diseases. BioMed Res. Int., 2017.","DOI":"10.1155\/2017\/9351507"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nature24628","article-title":"Salt-Responsive Gut Commensal Modulates T(H)17 Axis and Disease","volume":"551","author":"Wilck","year":"2017","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"ehaa946-2701","DOI":"10.1093\/ehjci\/ehaa946.2701","article-title":"Associations between gut microbiome, short chain fatty acids and blood pressure across ethnic groups: The HELIUS study","volume":"41","author":"Verhaar","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"12672","DOI":"10.1073\/pnas.1904099116","article-title":"Ruminococcus Gnavus, a Member of the Human Gut Microbiome Associated with Crohn\u2019s Disease, Produces an Inflammatory Polysaccharide","volume":"116","author":"Henke","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1039\/D2FO02928F","article-title":"Dietary intake of table olives exerts antihypertensive effects in association with changes in gut microbiota in spontaneously hypertensive rats","volume":"14","author":"Juan","year":"2023","journal-title":"Food Funct."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Lv, M., Liu, M., Zou, S., Yin, D., Lv, C., Li, F., and Wei, Y. (2023). Immune Enhancement of Clam Peptides on Immunosuppressed Mice Induced by Hydrocortisone. Molecules, 28.","DOI":"10.3390\/molecules28155709"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s11906-017-0731-4","article-title":"DOCA-Salt Hypertension: An Update","volume":"19","author":"Basting","year":"2017","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Wu, H., Jiang, L., Shum, T.-F., and Chiou, J. (2022). Elucidation of Anti-Hypertensive Mechanism by a Novel Lactobacillus rhamnosus AC1 Fermented Soymilk in the Deoxycorticosterone Acetate-Salt Hypertensive Rats. Nutrients, 14.","DOI":"10.3390\/nu14153174"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Panthiya, L., Tocharus, J., Onsa-Ard, A., Chaichompoo, W., Suksamrarn, A., and Tocharus, C. (2022). Hexahydrocurcumin Ameliorates Hypertensive and Vascular Remodeling in L-Name-Induced Rats. Biochim. Biophys. Acta Mol. Basis Dis., 1868.","DOI":"10.1016\/j.bbadis.2021.166317"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1159\/000445624","article-title":"Cardiac Contractility Modulation Attenuate Myocardial Fibrosis by Inhibiting Tgf-\u03921\/Smad3 Signaling Pathway in a Rabbit Model of Chronic Heart Failure","volume":"39","author":"Zhang","year":"2016","journal-title":"Cell Physiol. Biochem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/22\/7610\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:23:35Z","timestamp":1760131415000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/22\/7610"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,15]]},"references-count":52,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["molecules28227610"],"URL":"https:\/\/doi.org\/10.3390\/molecules28227610","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,15]]}}}